Egyptian Journal of Psychiatry

Transcription

Vol 33 No 1 January 2012
Table of contents
Editorial
1
New concept of depression and its management
Ahmed Okasha
Original articles
9
Gender differences in personality characteristics and cognitive abilities in adolescents admitted in correctional
institutes in Egypt
Amany Ahmed Abdou, Dalal Amer and Mohamed Nasreldin Sadek
15
The role of the brain-derived neurotrophic factors in the progression of bipolar disorders
Heba Fathy, Shereen Mohamed Abd El-Mawella, Hoda Abdou and Amal Abdou
19
Depression and Alzheimer disease: a risk factor or a prodrome
Hoda Salama, Tarek Molokhia, Hazem Maarouf and Hesham Sheshtawy
23
Gender-related phenomenological and neuropsychological differences in elderly patients with depression
Fatma Moussa, Mohamed Nasreldi, Hani Hamed and Amany Ahmed Abdou
29
Memory impairment in female schizophrenic patients and its relation with their female sex hormonal profile
Samia Abd EL-Rahman Ahmed, Ola Omar Shaheen, Amany Ahmed Abdou and Mohamed Nasr El Din
35
Impact of the first national campaign against the stigma of mental illness
Nahed Khairy, Emad Hamdi, Albert Sidrak, Noha Sabry, Mohamed Nasreldin, Aref Khoweiled and Nasser Loza
40
Cognitive functions in euthymic adolescents with juvenile bipolar disorder
Lamis El Ray, Aref Khoweiled, Hoda Abdou, Shreen Abd El-Mawella and Mai Abdel Samie
45
Quality of life and burden of women with premenstrual dysphoric disorder
Nagda M. El-Masry and Nelly R. Abdelfatah
Editorial Board
Editor-in- Chief
Momtaz Abdel-Wahab
Associate Editors
Mostafa Shaheen
Tarek Okasha
Tarek Asaad
Aref Kwaled
Co-Editor
Ahmed Abdel-Latif
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Ahmed Okasha
Emeritus Editors
Mahmoud Sami Abdel-Gawad
Yehia EL-Rakhawy
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National
Abdel Azeem, S.,
Abdel Hakeem, R.,
Abdel Mohsen, Y.
Abdel Rahman, S.,
Aboul Azayem, A.,
Aboul Magd, F.,
Ahmed, S.,
Arafa, M.,
Ashour, A.,
Bishry, Z.,
El Akabawy, A.S.,
El Atrouny, M.H.,
El-Dad A.,
El Gabry, M.,
El sheshai. A.,
Fahmy, E.,
Fahmy, M.,
Gad, S.,
Ghanem. M.,
Hadhoud, M.E.
Ismail, M.K.,
Khalil, A.H.,
Khashaba, A.,
Khater M.,
Lotaief, F.,
Loza. N.,
Mahfouz, R.,
Medani, A.,
Moursy, H.,
Sadek, A.,
Seif El Dawla, A.,
Shalaan, M.,
Youssef, I.
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Abdel Rahman, M. (Sudan)
Antun, F. (Lebanon)
Ansari, E. (Kuwait)
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El Assal, A. (Syria)
El Hammad. A. (KSA)
El kadry, A. (Iraq)
El Rowii, A. (Libya)
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El Takritti, A. (Jordan)
Erfan, M. (KSA)
Ghobash, R. (UAE)
Hadad, M. (Bahrain)
Kacha, F. (Algeria)
Kamel, C. (Bahrain)
Karam, E. (Lebanon)
Moussaoui, D. (Morocco)
Omara, E. (UAE)
Paes, M. (Morocco)
Sarhan, W. (Jordan)
Turky, J. (Tunisia)
International
Abdel Nasser, M. (UK)
Abou Saleh, M. (UK)
Akiskal H. (USA)
Amin. Y. (UK)
Cox, I. (UK)
Chaudry, H.R. (Pakistan)
Craig. T. (UK)
Christodoulou, G. (Greece)
Delgado. P. (USA)
El Gebali. N. (Canada)
Fawzi, F. (USA)
Hamdi. E. (UK)
Hindmarch, I. (UK)
Kasper, S. (Austria)
Leonard, B. (UK)
Lopez-lbor, I.J. (Spain)
Maj, M. (Italy)
Mezzich, J. (USA)
Ruiz, P. (USA)
Sartorius, N. (Switzerland)
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Editorial 1
New concept of depression and its management
Ahmed Okasha
WHO Collaborating Center for Research and Training in Mental Health, Okasha
Institute of Psychiatry, Ain Shams University, Cairo, Egypt
Correspondence to Ahmed Okasha MD, PhD, FRCP, FRC, Psych, FACP (Hon)
Director of WHO Collaborating Center for Research and Training in Mental Health
Okasha Institute of Psychiatry, Ain Shams University President Egyptian Psychiatric
Association Hon. President Arab Federation of Psychiatrists President of
WPA (2002-2005) Chairperson of WPA Ethics and Review Committee 3,
Shawarby Street, Kasr El Nil Cairo- Egypt
Tel: +(202) 29200900,1,2,3,4,5,6
fax: +(202) 29200907,8
e-mail: [email protected]; [email protected]
Received 1 July 2011
Accepted 22 September 2011
Egypt J Psychiatr 33:1–8
& 2012 Egyptian Journal of Psychiatry
1110-1105
Introduction
The prevalence of psychiatric disorders in the community
is high; out of every 100 citizens, 30% suffer from a mental
problem that needs attention, 20% will seek traditional
healers or general practitioners’ help, 10% will be
identified by the general practitioner as psychiatric cases,
only 2.3% will be referred to a psychiatrist, and 0.5% will
need inpatient treatment (Goldberg and Huxley, 1980).
The global burden of depression as measured by disabilityadjusted life years, that is, how many years are lost because
of illness and premature mortality was projected to be the
third in 2004 (Murray and Lopez, 1996). According to
information from WHO, depressive disorders are of high
socioeconomic and health-economic importance as these
psychiatric disorders most frequently cause psychosocial
disability. Despite intensive biologically oriented psychiatric research over the last few decades, the etiology of
depressive disorders is not yet fully understood, but a
multifactorial genesis is assumed and has been elucidated
in increasing detail. Besides psychological and social
factors, biological variables apparently play a major role,
which lead as a whole to a disturbed central nervous
homeostasis (Baghai et al., 2011).
Global disparity
Depression currently affects B121 million people worldwide. By 2020, depression is projected to become the
second highest contributor to the global burden of
disease in terms of disability-adjusted life years, whereas
by 2030, it will be the first highest contributor. Studies
suggest large geographical variations in the burden of
depression. Depression is a low priority in most lowincome to middle-income countries and there is apparently a higher incidence of depression in rural than in
urban areas (Sartorius et al., 1993; Prince et al., 2007).
The prevalence of depressive disorders in various patient
populations is estimated as follows: in the general
population 5.8%, chronically ill patients 9.4%, hospitalized patients 33.0%, geriatric inpatients 36.0%, cancer
outpatients 33.0%, cancer inpatients 42.0%, stroke
1110-1105 & 2012 Egyptian Journal of Psychiatry
patients 47.0%, myocardial infarction (MI) patients
45.0%, and Parkinson’s disease patients 39.0% (The
World Psychiatric Association, 2008).
Changing conceptualizations of major depressive disorder
(MDD) are shown by the differences between the past
clusters of situational versus endogenous depression and
the recent concept of interplay between biology and
environment. Previously, high treatment response rates
and full recovery were considered as the rule, nowadays,
depression is viewed as a progressive disorder with worse
outcomes over time. There was no known cell pathology
and a possible ‘chemical imbalance,’ but recently, evidence
of cellular pathology has been emerging. In treatment,
there was a wait-and-see attitude, with a habit-based
prescribing; however, now, aggressive, individualized treatment is followed (Aston-Jones et al., 2000).
When does depression become a mental disorder?
The Diagnostic and Statistical Manual of Mental Disorders
definition of MDD fails to exclude intense sadness arising
from the way human beings naturally respond to major
losses. ‘Normal’ sadness may therefore be treated as a
depressive disorder, which may undermine normal recovery
by disrupting normal coping processes and use of informal
support networks. Depression, in contrast to normal
sadness, is unrelated to a preceding event in the intensity,
duration, and degree of functional impairment it produces
(Maj, 2011). The experimental induction of depressed
mood has led to a significant increase in reports of recent
stressful events. The presence itself of a depressive state
may expose a person to adverse life events. Among patients
with a diagnosis of MDD, those with a score of less than 20
on the Hamilton Scale for Depression (who made up more
than 60% of the sample) did not recover more frequently
with imipramine than with placebo plus clinical management (Maj, 2011). The psychosocial impairment associated
with the presence of two to four depressive symptoms has
been repeatedly reported to be comparable with that
associated with the presence of five or more symptoms. The
threshold for a depressive state deserving clinical attention
may be lower than that fixed by the Diagnostic and Statistical
DOI: 10.7123/01.EJP.0000412301.27206.f1
2 Egyptian Journal of Psychiatry
Manual of Mental Disorders, fourth edition, but the threshold
for a depressive state requiring pharmacological treatment is
likely to be higher. These thresholds may need to be based
on the overall severity of depressive symptoms, rather than,
or in addition to, their number (Maj, 2011).
In medicine, the term depression has at least three
different meanings: (a) a mood, a feeling, an emotion, an
affective state; (b) a symptom of a depressive disorder;
and (c) the depressive disorder itself. This text
presentation focuses primarily on depressive disorders.
Essential features of depressive disorders
There are numerous types and variations of depressive
disorders, and differentiation is important for effective management. Depressive disorders share a number of clinical
manifestations: (a) mood and affect (diurnal rhythm): sadness, anxiety, decreased reactivity, tension, decreased motivation, irritability, emptiness, anger, apathy, and a sense of
frustration (The World Psychiatric Association, 2008), (b)
thought-cognition: decreased concentration, helplessness, indecisiveness, hopelessness, loss of confidence, pessimism,
decreased self-esteem, death wishes, inappropriate guilt, and
suicidal ideas, (c) psychomotor activity: (i) retardation: decreased body movements, stupor, decreased facial expression,
and decreased inhibited interpersonal communication, (ii)
agitation: restlessness, fidgeting, and purposeless uncontrollable hyperactivity (The World Psychiatric Association, 2008),
(d) somatic manifestations (masked depression) 50–70% of
depressed patients: (i) basic functions: insomnia (Early
Morning Wakening EMW) (Aka terminal insomnia), hypersomnia, appetite and body weight, sexual drive, (ii) vitality:
tiredness, fatigability, energy, and vigor, (iii) bodily sensations:
pains and aches, pressure, coldness, heavy limbs, any other
vague undifferentiated sensations, (iv) visceral symptoms:
gastrointestinal (GI) complaints, Cardio-Vascular (CV) complaints, and vague complaints about a bodily function (The
World Psychiatric Association, 2008).
Clinically, the main presentations of depression are
fatigue, lack of concentration, and painful bodily symptoms rather than depressive symptoms.
There are two questions for provisional diagnosis. (a) In
the past month, have you felt ‘down,’ depressed, or
hopeless? (b) In the past month, have you had little
pleasure or interest in doing things?
The test can identify 96% of patients with depression.
However, its specificity is only 57%; the clinician should
obtain additional information to substantiate the diagnosis (Whooley and Simon, 2000).
cancel out each other’s effects. Epigenetic modulation
explains that life events may influence gene expression.
Diathesis toward mood disorders is most likely a product
of a complex interaction of a large number of genes, with
minor individual effects and environmental factors as
shown in Fig. 1 (Maletic and Raison, 2009).
The interaction between genetic vulnerability affected
by stress or injury and influenced by epigenetic modulation can reinforce or extinguish the gene expression.
Multiple roles of brain-derived neurotrophic factor and
neurotrophic factors in mood disorders
Brain-derived neurotrophic factor (BDNF) and neurotrophic factors play a role in neurogenesis, neuroplasticity,
and neural resilience. It plays a central role in translating
functional into structural change and an important role in
neuroendocrine regulation. BDNF and other neurotrophic
factors may be altered in depression, anxiety, pain, and
mania. Successful treatment of mood disorders may restore
appropriate BDNF function (Dunn et al., 2005; Chen et al.,
2006; Cunha et al., 2006; Duman and Monteggia,
2006; Schule et al., 2006; Castren et al., 2007; Post, 2007).
Stress and 5-HTT polymorphism interaction may
precipitate depression
This study characterized the risk for major depression and
generalized anxiety syndrome as a function of serotonin
transporter (5-HTT) genotype, sex, and the occurrence of
all stressful life events. Individuals with two short (S)
alleles at the 5-HTT locus were more sensitive to the
depressogenic effects of all stressful life events than those
with one or two long (L) alleles (Kendler et al., 2005).
Cumulative effect of risk factors on depression
The following factors were investigated for contribution
to risk: serotonin transporter (5-HTTLPR) (locus
SLC6A4), BDNF (variant val66met), history of maltreatment, and social support.
There was a three-way interaction between the BDNF
genotype, 5-HTTLPR, and a history of maltreatment in
predicting depression. The vulnerability associated with
these two genetic factors was only evident in maltreated
children (Kaufman et al., 2006).
Figure 1
Epidemiological studies
(a) Lifetime prevalence: 16.6 US, 12.8 Europe, 16.0 New
Zealand, 7.2 Mexico, 3.3 Nigeria, (b) 12-month prevalence: 6.2 US, 3.9 Europe, 5.7 New Zealand, 3.7
Mexico, 1.0 Nigeria (Kessler et al., 2008).
Gene–environment interactions may play a role in the
etiology of mood disorders
Genetic epistasis means complex interactions between
the ‘vulnerability’ genes, whereby they potentiate or
Neurobiology of major depressive disorder (Maletic and Raison, 2009).
New concept of depression and its management Okasha 3
Impact of comorbid anxiety-depression
Greater symptom severity, more illness chronicity, increased risk of suicide, greater function impairment,
disability, poorer response to treatment, poorer prognosis,
excessive medical utilization, and poor quality of life.
Goldberg suggested for International Classification of
Diseases-11 (ICD-11) that the emotional disorders (internalizing) may all be similar and should be one cluster
instead of splitting them into many disorders, namely:
mood disorders: depression (nonpsychotic), dysthymic
disorders, neurotic, and stress-related disorders: specific
phobias, social phobias, generalized anxiety, panic disorder,
obsessional states, posttraumatic stress, somatoform disorders, neurasthenia, anxious, personality disorder, mixed
disorder of conduct and emotions, and phobic anxiety
disorder of childhood. He proceeds by explaining that,
among emotional disorders, the following are especially
important and similar: temperamental antecedents, rates of
comorbidity, genetic risk factors, symptom similarity,
course, treatment response, familiarity, environmental risk
factors, the neural substrate, cognitive, emotional processes, and biomarkers (Goldberg et al., 2009) (Fig. 2).
The severity of symptoms, diagnostic subtypes, and the
presence of specific symptoms, as well as age and
comorbidity, play a role in the course of illness and
choice of treatment. The treatment that provides the
highest likelihood of response and the best tolerability
should be preferred in treatment plans and algorithms.
Treatment of depressive disorders mostly consists of a
combination therapy, determined by the current clinical
features, the main constituents of a multimodal antidepressant therapy being pharmacotherapy, psychotherapy,
psychoeducation, and social support. Whereas pharmacotherapy is not always mandatory for less severe forms of
depression, moderate and severe depression usually
requires pharmacotherapy or electroconvulsive therapy
(ECT) in treatment-resistant illness (Baghai et al., 2011).
Figure 2
Depression/anxiety disorders comorbidity. [Lifetime prevalence of major
depressive disorder among individuals with lifetime diagnoses of each
anxiety disorder (Weissman et al., 1994; Wittchen et al., 1994; Kessler
et al., 1995; Magee et al., 1996; Roy-Byrne et al., 2000). GAD,
generalized anxiety disorder; OCD, obsessive compulsive disorder; PD,
personality disorder; PTSD, post traumatic stress disorder; SAD,
seasonal affective disorder.
A further problem in the pharmacotherapy of depression is
the latency of up to several weeks before the symptoms
begin to alleviate (Baghai et al., 2006), although a faster
onset of response has been reported for newer dual-acting
compounds such as mirtazapine (Leinonen et al.,
1999; Benkert et al., 2000) and venlafaxine (Benkert
et al., 1996; Montgomery, 1999). The fact that total or
partial sleep deprivation can produce a rapidly occurring
antidepressant effect in up to two-thirds of patients (Wu
et al., 1990) shows that it is indeed possible to achieve
antidepressant effects within a very short period. However,
these effects may not be strong enough and are usually not
sustained; thus, it is a clinical standard to strengthen them
using maintenance strategies such as multiple repetitions
of the sleep deprivation or subsequent phase advance
procedures (Wirz-Justice et al., 1999). Intravenous administration of the N-methyl-D-aspartate (NMDA) antagonist
ketamine has been shown to cause a rapid improvement in
mood in depressed patients (Zarate et al., 2006; Paul et al.,
2009; Price et al., 2009; Diazgranados et al., 2010a,
2010b; Larkin and Beautrais, 2011), but again, in most
cases, this effect is not persistent and may only be used as
an acceleration strategy. The only therapeutic intervention
that is more potent than sleep deprivation and leads to a
more rapid improvement than pharmacotherapy is ECT
(Gangadhar et al., 1982; ECT Review Group, 2003).
Unfortunately, transcranial magnetic stimulation and other
ways of stimulating the brain seem to be less effective
than ECT (Hasey, 2001; Eitan and Lerer, 2006; Slotema
et al., 2010).
In this text, we use the term efficacy to describe the
ability of an antidepressant to produce antidepressant
effects; by contrast, clinical effectiveness is the capability
and success of the treatment in achieving sufficient
amelioration of depressive symptoms in wider practice.
The definition of efficiency includes effectiveness
together with safety and tolerability as an important part
of the benefit/risk analysis of a treatment. In psychiatry,
the distinction between efficacy (outcome under ideal
use of a treatment) and clinical effectiveness (outcome
under typical use of a treatment) is often drawn. Whereas
efficacy may be shown in randomized double-blind
clinical trials, clinical effectiveness has to be demonstrated in the so-called effectiveness studies in wider
clinical practice (Baghai et al., 2011).
A further problem in the treatment of depression is the
nonresponse rate of approximately 30% (Charney et al.,
2002): the recent US STAR*D study found lower response
and remission rates even after multiple treatment trials
(Fava et al., 2006; Rush et al., 2009). High dropout rates
occur due to tolerability problems, which limit adherence,
complicate the successful treatment of depression, and
contribute to the high rate of nonresponse. Adequate
treatment comprises the use of a treatment with proven
efficacy over at least 4–6 weeks in a sufficient therapeutic
dose with reliable patient adherence (Sackeim, 2001; Fava,
2003; Kupfer and Charney, 2003), but following this
situation, approximately half of the patients do not respond
to a second antidepressant treatment trial. If several
antidepressant treatment trials have been unhelpful, even
lower response rates after switching to other approaches
may be expected (Fava et al., 2006). Others consider that it
should include combined treatment, for example, using two
antidepressants with divergent pharmacodynamic modes of
action or the use of two dually acting antidepressants that
may provide superior efficacy over antidepressant monotherapy (Bauer et al., 2009). Others argue that augmentation
approaches such as lithium augmentation or supplementation with cognitive behavioral therapy (CBT) and interpersonal psychotherapy are needed in addition, before
concluding that the condition is therapy resistant (Thase
et al., 1997). Other factors such as measuring treatment
adherence using therapeutic drug monitoring, determining
plasma concentrations of the prescribed antidepressants,
and deciding on the adequate dosage may also be included
in the definition of treatment-resistant illness.
mood symptoms in bipolar I disorder and over 90% of the
time spent with mood symptoms in bipolar II disorder
(Jamison, 2000; Judd et al., 2002, 2003).
The traditional definition of response to antidepressant
therapy is a 50% improvement in symptom severity,
whereas remission is defined as the virtual absence of
depressive symptoms and a full return to premorbid levels
of functioning (Thase, 2003). Besides clearly comprehensible biological factors underlying therapy resistance, such
as occult medical conditions, substance abuse interfering
with antidepressant treatments, or an abnormal metabolism (Rush et al., 2003), it is also hypothesized that
psychiatric comorbidities (Souery et al., 2007) and
psychosocial factors may be responsible for many failed
treatment trials (Grote and Frank, 2003).
(a) Stigma: one out of three patients with a depressive
disorder ever seeks medical help. (b) Masked depression:
many depressed patients present to physicians with
mainly somatic symptoms. In primary care settings, more
than half of the patients ultimately found to have a
depressive disorder originally presented with somatic
complaints: headache, backache, or vague, undifferentiated pain. (c) Comorbid medical illness: fatigue and loss
of appetite are common in both. (d) Tacit collusion:
physicians’ attitudes can also present obstacles to the
recognition of depression. (e) Time constraints. (f)
Inadequate medical education: many physicians currently
in practice receive only limited psychiatric education
during medical school or postgraduate training (Goldberg
and Lecrubier, 1995; Regier et al., 1998).
Currently available antidepressants are classified according to their chemical structure and their mode of action.
Currently, tricyclic antidepressant (TCA) and tetracyclic
antidepressant, selective and nonselective inhibitors of
monoamine oxidase, selective serotonin reuptake inhibitors (SSRI), selective noradrenaline reuptake inhibitors,
and antidepressants with a dual mode of action such as
selective serotonin and noradrenalin reuptake inhibitors
(SNRI), noradrenergic and specific serotonergic antidepressants, bupropion (Sartorius et al., 2007), and a
melatonergic MT1/MT2 receptor agonist with 5-HT2C
receptor antagonistic properties are available for use
(Kasper and Hamon, 2009). Current investigational
compounds include dopaminergic, serotonergic, and
noradrenergic triple reuptake inhibitors (SNDRI) that
have reached phase II clinical trials and glutamatergic
mechanisms (Kulkarni and Dhir, 2009) (Fig. 3).
The evolution of antidepressants is shown in the
following diagram (Andrews and Nemeroff,
1994; Slattery et al., 2004)
The following figure 4 shows the treatment gap worldwide in psychiatric disorders, with almost 50% of
depressed patients untreated.
Unipolar versus bipolar
Hantouche et al. (1998) found that 28% of a population of
depressed patients had bipolar disorders. Benazzi (1997)
found that 49% of the outpatients presenting with
depression had a bipolar spectrum disorder. Depression
represents about three quarters of the time spent with
The risks and consequences of misdiagnosis
Hirschfeld et al., 2003 noted that 69% of respondents
reported that they had initially been misdiagnosed as having
Unipolar Disorder (UD). Among the respondents to this survey, 35% reported that they had waited 10 years or longer to
receive a correct diagnosis. The issue of misdiagnosis is particularly serious because antidepressants used alone can lead
to induction of mania or acceleration of cycling frequency
over time, phenomena that have been reported to occur in
approximately 25–40% of patients with bipolar disorder
(Goldberg and Truman, 2003; Hirschfeld et al., 2003).
Obstacles to recognition of depression
The natural course of untreated depression shows that
after one year, 40% will recover, 20% will show partial
recovery (dysthymia), and 40% will remain depressed.
With antidepressants, we expect about 70% response and
30% nonresponse (Kupfer et al., 1992; Stahl, 2008).
Aim of treatment
Response is not sufficient: remission is the goal of
treatment. If residual symptoms are present (32%), there
is a need for vigorous and aggressive treatment. The
functional impact of residual symptoms should be taken
into account in the treatment plan. Pharmacotherapies
that increase Norepinephrine (NE) and/or Dopamine
(DA) neurotransmission may improve residual symptoms.
Therapeutic simple clinical approach:
(1) Psychotic depression: SGA + AD (SNRI or TCA) + ECT
(BST),
(2) Melancholic depression: AD (SNRI or TCA + ECT
(BST).
(3) Nonmelancholic depression: SSRI + CBT
(4) Painful depression: TCA or SNRI + CBT (ECTor BST)
(Parker and Hyett, 2009).
AD indicates antidepressants; BST, brain synchronization
therapy; SGA, second-generation antipsychotics.
Figure 3
Antidepressant started with Imipramine in 1957 and went through many stages, the last was Agomelatine and more are in the pipeline.
Figure 4
There are three treatment phases, namely, acute (6–12
weeks), continuation (4–9 months), and maintenance
(1 or more years).
Treatment with antidepressants in the acute phase
Treatment gap rates (%) by disorder (Kohn et al., 2004).
The adequate treatment should be used long enough to
establish whether it is effective. Once treatment with
antidepressant medication is initiated, the patient is
seen every 1 to 2 weeks, and more often if the patient
has severe depression or requires titration of a TCA.
Response to therapy (clearly better, not better) is
assessed at 6 weeks, although a patient may respond
earlier (The World Psychiatric Association, 2008).
All antidepressants are efficacious
Myocardial infarction
After an episode of major depression, the risk of MI
increases to fivefold. Subsyndromal forms of depression
have a twofold increased risk of MI. Six months after MI,
the mortality rate is about 17% in patients with
depression, whereas it is only 3% in patients without
depression. Twelve months after bypass show those with
depression had a higher incidence of subsequent cardiac
events, angina, heart failure, MI, repeat surgery. MD is a
significant risk factor for the development of coronary
artery disease and stroke (Frasure-Smit et al., 1993).
Criteria for choosing an antidepressant
The selection of antidepressants from more than 42 AD
depends on: (a) patient preference, (b) nature of prior
response to medication and family history, (c) relative
efficacy and effectiveness, (d) safety, (e) tolerability and
anticipated side effects, (f) adverse effects (sexual dysfunction – suicidal thoughts – weight, sedation, or anxiety – GI
symptoms), (g) potential drug interactions, (h) co-occurring
psychiatric or general medical conditions, (i) cognitive
functions, (j) type of depression, for example, painful,
melancholic, psychotic etcy, (k) half-life, and (l) cost.
There is 70–80% efficacy with any marketed antidepressants. SRIs or SNRI or Bupropion are excellent first-line
choices. TCAs may be superior for some ‘severe’ depressions.
Monoamine Oxidase Inhibitors (MAOIs) may be preferred
for some atypical depressions.
See Tables 1–4 for types of antidepressants.
Potential for drug interactions
Many medications are metabolized through the cytochrome P-450 enzyme pathway: co-administration can
lead to drug–drug interactions and can lead to clinically
significant effects, increased side effects, and decreased
effectiveness, Use Antidepressants (AD) with the least
drug–drug interaction, for example, Sertraline, Ecitalopram, Mianserin, that is, no induction or inhibition of
liver enzymes (Preskorn et al., 2008) (Table 5).
Interaction with cardiac medications
SSRIs may increase blood levels of b blockers, and
anticoagulants, for example, warfarin, and other cardiac
medications through cytochrome P-450 isoenzyme inhibition. Least escitalopram, Mirtazepine, venlafaxine,
Table 1 Mixed serotonin norepinephrine tricyclic antidepressants: (The World Psychiatric Association, 2008)
Drugs
Amitryptiline
Amitriptylinoxide
Dibenzepine
Dosulepine/
dothiepin
Doxepin
Imipramine
Melitracen
Protriptyline
Clomipramine
25–75
30–60
120–180
75
150–300
180–300
240–720
75–150
25–75
25–75
20
10
25–50
150–300
150–300
20–30
20–60
100–250
Table 2 Monoamine oxidase inhibitors and reversible inhibitors
of monoamine oxidase (The World Psychiatric Association,
2008)
Phenelzine
Isocarboxacid
Tranylcypromine
Moclobemide1
Starting dose (mg/day)*
Dose range (mg/day)*
15
20
10
150–300
30–40
20–60
20–40
300–600
*Dosages recommended by the producer.
Table 3 Serotonin–norepinephrine reuptake inhibitor (The
World Psychiatric Association, 2008)
Drugs
Venlafaxine
75
Duloxetine
40/602
Milnacipram
50
Noradrenalin reuptake inhibitor
Reboxetine
4
2D6
1A2
2C19
2C9
75–375
60–120
100–200
8–12
Table 4 Modulating antidepressants (The World Psychiatric
Association, 2008)
Venlafaxine
Citalopram
Fluoxetine
Paroxetine
Escitalopram
Fluvoxamine
Sertraline
0
0
++
+
0
++
+
0/ +
+
+++
+++
+
+
+
0
+
+
+
0
+++
+
0
0
++
+
0
+++
++
0
0
++
+
0
++
+
0, negligible; + , very weak interaction; + + , moderate interaction;
+ + + , strong interaction.
3A4: Ca + antagonists, erythromycin, ketoconazole, lidocaine, cancer
therapies.
2D6: Antiarrhythmic, b-blockers, haloperidol, neuroleptics.
1A2: caffeine, ciprofloxacin, theophylline, verapamil.
2C19: diazepam, propranolol, moclobemide, imipramine.
2C9: miconazole, phenytoin, S-warfarin, NSAIDs (Greenblatt et al.,
1998; Alberts et al., 2000; Von Moltke et al., 2001).
General dosing strategy
The general dosing strategy involves avoidance of
frequent dose increases but making contact with the
patient every 1–2 weeks, waiting for 2–4 weeks with a
total nonresponse (or a partial response that has
plateaued) before increasing the dose. The medication
can be changed if there is no response after 4 weeks;
however, when clinically necessary, the change may have
to be made earlier than 4 weeks and wait 8–12 weeks if a
gradual response has not plateaued.
Drugs
3A4
Starting dose (mg/day)* Dose range (mg/day)*
Drugs
Table 5 Potentials for drug–drug interactions
Modulating antidepressants
Trazodone
50–100
200–600
Nefazodone3
100
300–600
Dopamine and noradrenalin reuptake inhibitors
Bupropion
100
200–300
Noradrenergic and specific serotonergic antidepressants
Mianserin
30
60–120
Mirtazapine
15
30–45
Melatonergic antidepressants
Agomelatine
25
25–50
duloxetine. Agomelatin and SSRIs may also reduce
platelet aggregation. Patients who receive concomitant
aspirin or warfarin may bruise or bleed easily and may
require dosage reductions or medication changes.
‘Common’ serotonin reuptake inhibitor adverse effects
Common adverse effects of SRI include GI disturbances,
headache changes, sleep disturbances, appetite changes,
sexual function changes, anxiety level changes, allergic
reactions, and rarely bleeding and hyponitremia.
Antidepressant treatment trials in patients with chronic
medical illness
Major depression is responsive to antidepressant treatment in patients with cancer, chronic tinnitus, chronic
obstructive pulmonary disease (COPD), diabetes, inpatient rehabilitation needs, ischemic heart disease, Parkinson’s disease, rheumatoid arthritis, stroke, and HIV +
(Katon and Sullivan, 1990).
Formal psychotherapy used in combination with
antidepressants
Combination treatment may be useful if either treatment
alone is only partially effective. The clinical circumstances
suggest two different and discrete targets of therapy (e.g.
symptom reduction to be addressed with medication and
psychological/social/occupational problems to be addressed
with formal psychotherapy). Targeted psychotherapy of
depression (e.g. cognitive, behavioral, IPT of depression)
does not have the physiological side effects associated with
medications. It should be kept in mind that psychotherapy
is composed of 70% ventilation, 20% exploration, and 10%
suggestion, guidance reassurance.
Brain synchronization therapy and electroconvulsive
therapy
ECT provides rapid symptom relief, which is especially
useful in severely ill suicidal patients, refractory to other
treatments, psychotic, melancholic patients, and when a
patient’s medical condition makes drug therapy risky.
Treatment of depression in the new millennium
Other potential antidepressants such as tachykinin, glucocorticoid, and corticotropin-releasing factor-1 receptor
antagonists have not fulfilled expectations, although newer
mechanisms such as L-arginine-nitric oxidecyclic guanosine
monophosphate pathway modulators, sigma-1 receptor
modulators, neurosteroids, 5-HT6 and 5-HT7 serotonin
receptor antagonists, b3-adrenoceptor antagonists, and
vasopressin receptor antagonists, as well as some potentially
new herbal antidepressants, have not yet been assessed
beyond animal experiments (Kulkarni and Dhir, 2009).
Further investigation of these potentially new treatment
options is of major importance, in order to provide better
strategies for the clinical management of depression.
(1) Cell surface: drugs designed for specific receptors
(NRI, noradrenergic and specific serotonergic antidepressant, norepinephrime and dopamine disinhibitors), blockade of 5HTC2 (agomelatine).
(2) Intracellular: drugs acting on second messenger
transduction, transcription.
(3) New modalities: drugs to suppress HypothalamicPituitary-Adrenal (HPA) axis hyperactivation, glucocorticoid production Corticotropin- releasing factor
(CRF), substance P inhibition (neurokinin-antagonist), b 3 receptors [regulate neural activity in the
ventral medial prefrontal cortex (vmPFC)], drugs
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Conclusion
Improving the quality of life of depressed patients
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from normal sadness. The selection of one of the 42
available AD requires the psychiatrist to be abreast of
knowledge for treating comorbid physical and mental
disorders. The first line of treatment, whether medications or psychotherapy, will determine the well-being of
the depressed patients. Psychiatrists nowadays are
satisfied with the patient being ‘better’ but not ‘well’.
The aim of treatment should be remission. Response is
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Conflicts of interest
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Original article 9
Gender differences in personality characteristics and
cognitive abilities in adolescents admitted in correctional
institutes in Egypt
Amany Ahmed Abdou, Dalal Amer and Mohamed Nasreldin Sadek
Faculty of Medicine, Cairo University, Cairo, Egypt
Correspondence to Amany Ahmed Abdou, Assistant
Professor of Psychiatry, Faculty of Medicine, Cairo
University, Cairo, Egypt
Tel: + 0100 5214720;
e-mail: [email protected]
Accepted 22 August 2011
Egyptian Journal of Psychiatry 2012, 33:9–14
Objectives
To ascertain differences between male and female adolescents admitted
to correctional institutes in Egypt with respect to their personality
characteristics and cognitive abilities.
Methods
This cross-sectional study was carried out in two correctional institutes in Cairo.
Fifty adolescents admitted after being convicted by court (25 male, 25 female)
were randomly selected, assessed, and compared with an age-matched control group
(N = 25). Data on personal, sociodemographic, and criminal history were collected.
They were subjected to the Wechsler Adult Intelligence Scale, the Wisconsin Card
Sorting Test, the Eysenck Personality Questionnaire, The Hostility Questionnaire,
and the Psychiatric Symptomatology Scale for adolescents.
Results
Of the students, 28% were male and 16% were female; 72% of male and 36% of
female adolescents were working as unskilled manual workers. Male adolescents were
more violent in their acts compared with female adolescents (48 vs. 8%); 12% of male
adolescents were engaged in the use and sale of drugs compared with 8% of female
adolescents; 44% of female adolescents were homeless compared with 4% of male
adolescents; stress factors were mostly financial in male adolescents (88%), whereas
in females sexual abuse was present in 24% in addition. Substance abuse was a
dominant feature in both: 80% in male adolescents (nicotine smoking in 24% and
polysubstance in 56%) and 64% in female adolescents (nicotine smoking in 44%
and polysubstance in 20%). Adolescent girls had significantly higher scores in the
adjustment disorder, identity disorder, and depression, bulimia, and sleep disorders
on the symptomatology scale. They also had lower IQ in the total, verbal, performance,
vocabulary, arithmetic, digit span, digit symbol, and block design scales of the
Wechsler Adult Intelligence Scale. No significant difference was seen in the Eysenck
Personality Questionnaire and in the Wisconsin Card Sorting Test.
Keywords:
adolescents, correctional institutes, personality characteristics and cognitive abilities,
sex-related differences
1110-1105
Introduction
Adolescent delinquency is an important public health
problem; it varies from outright aggression to other
antisocial behaviors such as steeling and vandalism. The
National Center for Social and Criminal Studies (2002)
showed a marked increase in delinquent behavior among
adolescents; for example, school violence rate increased
from 4.9% in 1995 to 5.5% in 2000. In addition, police
reports for adolescent delinquency showed a significant
increase in incidence from 1056 acts in 1991 through 2083
acts in 1997 to 3069 acts in 2001 (The National Center for
Social and Criminal Studies, 2002).
In a recent report on adolescent crimes in Egypt, drugs
constituted 72.5% of the majority of crimes committed in
2001, followed by carrying armed weapon in 14.4% and
crimes related to violence (murder, rape, battery leading
to death, armed robbery, kidnapping, arson, etc.) constituting 11.3%. In contrast, 25% of all the children and
adolescents arrested in Egypt in 2001 were arrested on the
charge of being ‘vulnerable to delinquency’ (Ministry of
Interior, Social Protection Sector, General Administration
for Juvenile Welfare Investigation, 2002).
Male and female juvenile delinquents showed differences in
behavioral, psychopathological, and familial risks, psychiatric
perspective, and functional impairment.
Girls commit fewer and less serious offences and they are
younger than detained boys when admitted to correctional institutes. Girls also experience greater incidences
of physical, emotional, and sexual abuse, physical neglect,
and family history of mental illness compared with their
DOI: 10.7123/01.EJP.0000411074.34042.8e
male counterparts. A relatively high percentage of
mentally challenged girls were found among those
admitted to correctional institutes (McCabe et al., 2002).
Female offenders have more acute mental health
symptoms and psychological disturbances than do male
offenders (Espelage et al., 2003).
In addition, multiple sexual contacts from an early age,
substance abuse, running away from home, and truancy
were found to be behaviors leading to risk of development
of juvenile delinquency in girls (Lenssen et al., 2000).
(4) The Hostility Questionnaire: It consists of 51 questions, covering different aspects of hostility (overt, selfcriticism, other’s criticism, paranoid aggression, guilt
feelings, and the total score) (El Taieb, 1984).
(5) The Wisconsin Card Sorting Test (WCST): It is a tool
for recognizing frontal cortical dysfunction. It consists
of 64 cards and four meaningless stimulus cards.
These have to be sorted one at a time with these
stimulus cards. The first principle is ‘color,’ the
second is ‘figure’ or ‘form,’ the third is ‘number’ and
so on. Thirteen indices were chosen for assessment
(Heaton et al., 1993).
Aim of the work
NB
This work aimed to find out the sex-related differences
between adolescents admitted to correctional institutes
in Egypt with respect to their personality characteristics
and cognitive abilities, which may have implications in
the management and choice of rehabilitation programs.
For all the previous tools we used the Arabic version, which
was standardized and adapted to suit the Egyptian culture;
their validity and reliability were proven. We used a control
group (N = 25) that was matched with the adolescent
delinquent group in age only. The members of the control
group were selected from educated volunteers from Kasr El
Aini worker relatives. This was not for comparison, as in fact
the adolescent delinquent group cannot be compared with
any normal adolescent group because their characteristics
will never simulate any normal adolescents in any aspect,
such as socioeconomic status (SES), familial background,
intelligence, education, psychiatric symptoms, hostility, etc.
However, this comparison was helpful to compare the
results of adolescent delinquents obtained from the
different questionnaires with the results of age-matched
normal adolescents so as to give us a true idea about the
actual results and limitations.
Participants and methods
This is a cross-sectional study. It was carried out in two
correctional institutes in Cairo, one for boys (Ain Shams)
and the other for girls (El Agouza), under the supervision
of the Ministry of Social affairs after obtaining approval
from the legal authority. These adolescents were admitted
after being convicted by court following criminal or
delinquent acts. Fifty juvenile delinquents (25 boys and
25 girls) were randomly selected, as we included the
middle family and the older age group families in both
institutes. The children were divided into families
according to their ages. They were accused of a heterogenous group of crimes. Their personal, sociodemographic,
and criminal histories were collected after interviewing
them, the supervisors, and the social worker of each family
and also from institution documents. All the adolescents
included were willing to participate in the study. The few
cases that refused were excluded.
They were subjected to the following:
(1) The Wechsler Adult Intelligence Scale – Revised
(WAIS-R) (the subscales and the verbal, performance, and total scores): Analysis of WAIS-R by its
detailed subscales was carried out to assess different
cognitive domains covered by the scale (Melikah and
Ismael, 1967).
(2) The Eysenck Personality Questionnaire: This questionnaire consists of psychoticism (P), neuroticism
(N), extraversion (E), introversion (I), lie (L), and
psychopathic deviation (PD) scales, in adult form
(Abou Nahia, 1989).
(3) The Psychiatric Symptomatology Scale, for adolescents and adults: It is a structured tool prepared
according to the Diagnostic and Statistical Manual of
Mental Disorders third edition-revised criteria and
ICD-10 criteria. It consists of 150 questions, screening most of the psychiatric symptoms (27 symptoms)
(Hamouda and Emam, 1996).
Statistical methods
Data were computerized and analyzed using the software
package SPSS (version 11 IBM, Armonk, New York, USA).
Frequency distribution was used to describe the included
participants on the basis of their qualitative parameters,
whereas mean and SD + was used to describe the
quantitative parameters. Differences between boys and
girls among both cases and controls were explored using the
w2-test (when relevant) for qualitative data and using the
Student t-test for quantitative data. Levels of significance
in all statistical tests was considered at Po0.05.
Results
The total number of adolescent delinquents was 50; 25
were male (50%) and 25 were female (50%). The control
(C) group consisted of 25 normal adolescents, of whom 15
were male (60%) and 10 were female (40%) (Table 1).
Both groups were age matched, with no statistically
significant difference between them. There was no significant difference in the SES between the groups;
significant difference was observed in education and
occupation. Twenty-eight percent of male adolescents
were students versus 16% of female adolescents; 72% of
male versus 36% of female adolescents were working as
unskilled manual workers (Table 2). Boys were admitted
Gender differences in personality characteristics Abdou et al. 11
Table 1 Sex difference in age
Table 3 Sex difference in legal data
Cases (50)
Males
(25)
Mean SD
Control (25)
Females
(25)
Mean
SD
Males
(15)
P
Females
(10)
Mean SD
Mean
Age 17.86 1.79 17.32 2.08 0.32 17.87 0.83 17.3
SD
P
1.06 0.15
Type of confinement
r3 years
5 years
Open
Accusation
Nonviolent
Violent
Drug use or selling
Homeless
Description
Planned
Impulsive
Homeless
Description
Solitary
Group
Males (N = 25)
Females (N = 25)
No. (%)
No. (%)
P
1 (4)
5 (20)
19 (76)
12 (48)
9 (36)
4 (16)
0.000**
9
12
3
1
10
2
2
11
(36)
(48)
(12)
(4)
(40)
(8)
(8)
(44)
0.001*
for a longer duration; they were more violent in their acts
(48 vs. 8% of girls) (Table 3). Stress factors were mostly
financial in boys (88%), whereas in girls sexual abuse was
present in 24% (Table 4). Substance abuse was a dominant
feature in both: 80% of boys (nicotine smoking in 24% and
polysubstance in 56%) and 64% of girls (nicotine smoking
in 44% and polysubstance in 20%) (Table 4). There was a
statistically significant difference between male and female
adolescents in the symptomatology scale; girls showed
significantly higher scores in adjustment disorder, depression, identity disorder, bulimia, and sleep disorders.
Adjustment disorder was present in 80% of girls versus
48% of boys; depression was present in 80% of girls versus
48% of boys; identity disorder was seen in 84% of girls
versus 48% of boys; bulimia was present in 48% of girls
versus 4% of boys; and sleep disorders and nightmares
were found in 60% of girls versus 24% of boys. There was
no statistically significant difference between male and
female adolescents in the rest of the subscales of the
symptomatology scale. Girls had significantly higher scores
in the Hostility Questionnaire covering different aspects
of hostility (overt, self-criticism, other’s criticism, paranoid aggression, guilt feelings, and the total score)
(Table 5). No significant difference was observed between
the groups with respect to personality characteristics as
measured by the Eysenck Personality Questionnaire in all
the subscales: extraversion, neuroticism, psychoticism,
and psychopathic deviation (Table 5). Girls had lower IQ
in the total, verbal, performance, vocabulary, arithmetic,
digit span, digit symbol, and block design scales of the
WAIS (Table 6). No significant difference was observed
between the groups with respect to cognitive abilities
such as frontal lobe functions and mental flexibility as
measured by WCST. No significant difference was
observed between boys and girls in any of the subscales
of WCST with regard to their frontal lobe functions and
mental flexibility (Table 7).
Table 2 Sex difference in sociodemographic data
Table 4 Sex difference in clinical characteristics
Residence
Urban
Rural
Education
Illiterate
Primary
Preparatory
Secondary
University
Occupation
Not working
Student
Unskilled
SES
Very poor
Below average
Average
Above average
Males (N = 25)
Females (N = 25)
No. (%)
No. (%)
P
20 (80)
5 (20)
18 (72)
7 (28)
0.74
5
6
11
3
0
(20)
(24)
(44)
(12)
(0)
4
8
9
3
1
(16)
(32)
(36)
(12)
(4)
0 (0)
7 (28)
18 (72)
12 (48)
4 (16)
9 (36)
8
10
7
0
15
7
2
1
SES, socioeconomic status.
**Highly significant.
(32)
(40)
(28)
(0)
(60)
(28)
(8)
(4)
0.81
0.000**
0.092
1 (4)
10 (40)
14 (56)
11 (44)
8 (32)
6 (24)
9 (36)
16 (64)
15 (60)
10 (40)
0.003*
0.156
*Significant.
**Highly significant.
Discussion
Sex-related differences among delinquent adolescents
have implications on the choice of management plans
applied in correctional institutes (Van Wijk et al.,
2007; Vincent et al., 2008). In our work (Table 2) male
and female juvenile adolescents showed no statistically
significant difference with respect to residence, education, and SES. This was expected as poor social and
Stress factors
Absent
Social and financial
Positive sexual abuse
Family history
Negative
Positive
Self-injury
Absent
Present
Suicide
Sexual practices
Negative
Homosexual
Heterosexual
Substance abuse
Negative
Nicotine only
Polysubstance
*Significant.
Males (N = 25)
Females (N = 25)
No. (%)
No. (%)
P
3 (12)
22 (88)
0 (0)
3 (12)
16 (64)
6 (24)
0.031*
15 (60)
10 (40)
14 (56)
11 (44)
1.000
19 (76)
3 (12)
3 (12)
18 (72)
1 (4)
6 (24)
0.36
15 (60)
5 (20)
5 (20)
13 (52)
6 (24)
6 (24)
0.85
5 (20)
6 (24)
14 (56)
9 (36)
11 (44)
5 (20)
0.032*
Table 5 Sex difference in personality characteristics (Eysenck Personality Questionnaire) and The Hostility Questionnaire
Cases (50)
Males (25)
EPQ
E
N
P
L
PD
Total hostility
Control (25)
Females (25)
Males (15)
Females (10)
Mean
SD
Mean
SD
P
Mean
SD
Mean
SD
P
14.08
16.40
7.36
9.84
15.32
22.56
5.28
3.44
2.77
2.54
2.59
6.56
12.96
16.28
8.64
8.48
15.24
26.56
4.95
4.23
2.72
2.77
2.38
7.25
0.44
0.91
0.11
0.08
0.91
0.046*
10.87
12.60
4.67
9.00
7.27
22.2
2.83
3.14
1.54
2.34
1.98
7.25
10.5
13
4
8.7
5.8
16.22
2.72
4.57
1.7
1.25
1.81
7.41
0.75
0.8
0.32
0.70
0.07
0.065
E, extraversion; EPQ, Eysenck Personality Questionnaire; L, lie; N, neuroticism; P, psychoticism; PD, psychopathic deviation.
*Significant.
Table 6 Sex difference in intelligence
Cases (50)
Males (25)
Total IQ
Verbal IQ
Performance
Performance subscales
Digit symbol
Object assembly
Block design
Picture completion
Picture arrangement
Verbal subscales
Vocabulary
Similarities
Arithmetic
Digit span
Comprehension
Information
Control (25)
Females (25)
Males (15)
Females (10)
Mean
SD
Mean
SD
P
Mean
SD
Mean
SD
P
80.08
76.80
85.08
6.86
7.04
9.37
71.80
68.56
78.52
11.99
10.57
14.38
0.005*
0.002*
0.063
102.33
101.0
102.32
3.811
5.92
2.58
101.50
96.00
102.50
2.64
3.16
1.58
0.53
0.012*
0.84
9.12
7.36
7.68
8.28
8.12
2.01
2.71
2.34
1.37
2.13
7.56
7.12
5.72
8.36
7.92
2.93
2.89
2.11
2.89
2.72
0.034*
0.763
0.003*
0.901
0.774
11
9.67
9.33
13
11.67
0.85
0.49
0.49
0.85
0.49
11
10.50
9.00
13
10.5
1.05
1.58
0.000
0.000
1.58
1.00
0.14
0.019*
1.000
0.047*
8.04
6.28
6.04
8.44
8.52
4.40
1.57
1.49
2.05
2.24
2.45
1.12
4.76
6.52
3.92
5.56
7.64
4.28
1.81
2.69
2.52
3.12
3.17
1.95
0.000*
0.699
0.002*
0.001*
0.278
0.791
10.67
11.67
9.33
9.67
13
10
0.49
0.98
1.76
1.76
0.85
0.85
9.5
11
8
11.5
11
12
0.53
1.05
0.000
0.53
1.05
0.000
0.000*
0.128
0.011*
0.001*
0.000*
0.000*
*Significant.
Table 7 Sex difference in The Wisconsin Card Sorting Test
Cases (50)
Males (25)
No. of trials administered
No. of categories completed
Total no. correct
Total no. of errors
% Errors
Perseverative responses
% Perseverative responses
Perseverative errors
% Perseverative errors
Nonperseverative errors
% Nonperseverative errors
Conceptual level response
% Conceptual level response
Trial to complete the first set
Failure to maintain set
Control (25)
Females (25)
Males (15)
Females (10)
Mean
SD
Mean
SD
P
Mean
SD
Mean
SD
P
12.08
4.12
74
47.5
38.7
33
25.96
25.04
20.04
22.12
18.08
55.84
47.7
18.40
1.00
13.83
1.86
12.6
17.68
12.66
27.11
21.13
17.84
13.62
8.64
6.24
15.13
17.17
12.04
1.53
121.8
3.56
73.48
51.24
40.8
22.6
19.0
26.6
21.16
24.2
19.56
52.88
44.68
16.56
1.12
13.77
1.69
13.19
20.62
14.92
19.04
16.55
15.48
11.78
8.17
5.7
16.34
17.58
9.12
1.33
0.81
0.27
0.89
0.50
0.60
0.12
0.20
0.74
0.76
0.39
0.39
0.51
0.439
0.545
0.769
105
5.13
77.8
38.6
30.8
9.2
7.8
21.93
13.47
16.07
13.13
65.47
61.27
16.4
0.93
21.07
1.06
8.95
16.77
10.19
10.14
8.52
10.55
6.10
8.4
6.09
10.9
14.02
10.66
1.22
93.2
5.80
73.00
15.80
16.50
9.10
10.50
11.30
6.7
6.8
6.7
66.3
77.1
13.9
0.70
25.08
0.63
14.45
8.65
5.86
10.14
13.12
7.10
5.03
5.69
5.03
10.08
8.67
6.44
1.25
0.22
0.09
0.31
0.001*
0.001*
0.98
0.54
0.011*
0.008*
0.006*
0.011*
0.85
0.004*
0.51
0.648
*Significant.
economic status affects male and female adolescents
equally. Although more boys attend school as families
tend to educate boys more than girls, it was not apparent
in our work as boys have more tendency for truancy and
drop out of school more. This agrees with the results
found in the present study that showed that both male
and female delinquents were from low SES (Van Wijk
et al., 2007; Townsend et al., 2010) with more tendency for
Gender differences in personality characteristics Abdou et al. 13
truancy in boys (Handwerk et al., 2006). Regarding
occupation, there was a significant difference, as 72% of
boys were working as unskilled manual workers versus
36% of girls, as many children who terminate their
education because of deviant behavior work as unskilled
manual workers, which is the most fitting work for their
skills. The reverse is also true, as many children whose
low SES force them to work early in their life will be
subjected to more stress factors, physical and sexual
abuse, and early substance availability and use, making
them more vulnerable to delinquency (Faied, 2002). Our
culture accepts the phenomenon of early occupation in
children because of poverty, which is rejected and
forbidden in developed countries. The boys tend to work
in workshops, whereas girls work as housemaids (Faied,
2002; Nasr, 2002). A statistically significant difference
between male and female adolescents was noted (Table 3)
regarding their legal data, as 76% of male adolescents
received open admission until they reached 21 years of
age, 20% for 5 years, and only 4% for 3 years (i.e. boys
were admitted for longer duration). In contrast, only 16%
of girls received open admission until they reached
21 years of age, 36% for 5 years, and 48% for 3 years (i.e.
girls were admitted for shorter duration). Violent acts
(e.g. murder, rape, battery leading to death, armed
robbery, kidnapping, arson) were seen in 48% of boys
versus 8% of girls, drug use or selling was seen in 12% of
boys versus 8% of girls, and homelessness constituted
44% in girls versus 4% in boys. Planned acts were
observed in 44% of girls versus 4% of boys, whereas
impulsive acts were 40% in boys versus 32% in girls; this
agrees with most of the previous studies (Abdou,
2005; Sadeq, 2005; Townsend et al., 2010). There was a
statistically significant difference between male and
female adolescents (Table 4) with regard to the presence
of stress factors. Eighty-eight percent of boys were
exposed to social and financial stress compared with
64% of girls; 24% of girls were additionally exposed to
sexual abuse. This result agreed with previous studies
(Faied, 2002; Nasr, 2002; Van Wijk et al., 2007) that found
that girls experienced greater incidence of physical,
emotional, and sexual abuse. It was obvious during the
interview, as 20% of girls refused to leave the institute
and asked for readmission at the end of their stay to
escape from their very traumatizing family environment.
Substance abuse showed a statistically significant difference between male and female delinquent adolescents; it
reached 80% in boys, whereas it was 64% in girls. Nicotine
use alone was 24% in boys and 44% in girls, whereas
polysubstance abuse was 56% in boys and 20% in girls
(cannabis, benzodiazepines, volatile substances, and
alcohol were the most commonly used) (Table 4). The
comorbidity of substance abuse and delinquency is a
worldwide phenomenon. Most of the studies found more
incidence of polysubstance abuse in boys than in girls, in
agreement with previous Egyptian studies (Abdou,
2005; Sadeq, 2005; Amer, 2007). This is in contrast to
the study (McCabe et al., 2002) that found no sex-related
differences regarding comorbid substance abuse between
boys and girls among adolescent delinquents, which could
be explained by the different sample sizes. Delinquent
girls had statistically significant higher scores on the
symptomatology scale with regard to adjustment disorder,
depression, identity disorder, bulimia, and sleep disorders. These results agreed with previous studies that
found that girls had higher rates of depression, hopelessness, negative self-evaluation, and suicide ideation
scores (McClelland et al., 2004; Ogden and Amlund
Hagen, 2009). It is important to mention that depression
may not be just a comorbid symptom, or a result of their
condition. It may be a cause, as in many cases the
disruptive behavior in children and adolescents may be an
expression of their depression and anxiety in an atypical
form (Abram et al., 2008). This is in contrast to the study
by McCabe et al. (2002) that found no sex-related
differences in comorbid symptoms between boys and
girls among adolescent delinquents. In this study,
personality characteristics (Table 5) showed no significant difference between boys and girls in all subscales of
the Eysenck Personality Questionnaire (extraversion,
neuroticism, psychoticism, and psychopathic deviation),
although significant differences between the study group
and control group regarding personality characteristics
using the EPQ (extraversion, neuroticism, and psychoticism scales, and psychopathic deviation) were reported in
previous studies (Abdou, 2005; Sadeq, 2005; Amer, 2007).
This is considered as a disease-specific finding rather
than sex specific; that is, it is related to the delinquent
behavior itself (impulsiveness, aggression, psychopathic
deviation, extraversion, neuroticism, and psychoticism)
and not to the sex of the offender (Table 5). These
results also agreed with the studies (McCabe et al.,
2002; Espelage et al., 2003) that found no significant
difference in the personality profile except for the
psychopathic deviation scale, which was more elevated
in boys than in girls (Vincent et al., 2008). On the contrary,
delinquent girls showed statistically significantly higher
scores in the Hostility Questionnaire covering different
aspects of hostility, which may be explained by the fact
that female delinquents tend to use hostility as a form of
defense mechanism to reduce their psychological pain.
Girls scored lower than boys (Table 6) with respect to
total, verbal, and performance IQ. This may be explained
by the fact that girls are less educated in our culture as
poor families are less likely to send their girls to school
and to continue education. In addition, low IQ is one of
the risk factors among girls for early delinquency, running
away from school, sexual abuse, and substance abuse
(Ministry of Interior, Social Protection Sector, General
Administration for Juvenile Welfare Investigation, 2001).
Although delinquent girls scored higher than boys along
the different subscales of hostility, namely, overt hostility,
self-criticism, other’s criticism, paranoid aggression, and
guilt feelings, the percentage of boys who received open
admission was significantly more than that of girls as they
committed more violent and serious crimes requiring
higher IQ. On analyzing the subscales of WAIS-R in detail
to assess different cognitive domains, it was seen that
girls also scored lower than boys in general vocabulary
normally available to growing individuals in the society,
which might be an indicator of the mental abilities and
awareness of the surrounding world, reflecting lower
verbal abilities stemming from lower IQ and lower
cultural and educational level. The arithmetic subscale,
in addition of assessing arithmetic abilities, assesses
immediate memory, concentration, and conceptual manipulation, reflecting lower conceptual abilities and
attention span in girls, which is matched with their lower
IQ and lower educational level. With regard to digit span
subscale assessing attention and immediate memory, girls
scored lower than boys, reflecting their shorter attention
span and distractibility. Although no significant difference
was noted when comparing attention deficit hyperactivity
disorder using the symptomatology scale, girls showed
higher depression and anxiety symptoms, which might
have an impact on performance. Digit symbol assesses
visuo-motor coordination. Delinquent girls scored significantly lower than boys. The scores of this scale are
affected by the speed and accuracy of performance, which
is affected by attention deficit and anxiety levels, both of
which were high among girls. The block design subscale
assesses visuo-constructive abilities, especially spatial
perception and nonverbal concept formation. In this
study, performance of delinquent girls was significantly
lower than that of boys, reflecting more impairment of
visuo-spatial abilities. However, the results of this test
could be affected by interests and motivation. The higher
depression and anxiety seen in the female delinquent
group might have had an impact on the results. No
significant difference was observed between boys and
girls in any of the subscales of the WCST (Table 7)
measuring their frontal lobe functions and mental
flexibility. This may be explained by the fact that this
pathology in brain functioning is disease specific rather
than sex related, as in the previous study (Sadeq, 2005).
Examining the cognitive functions in adolescent delinquents using the same tool, it was found that the
delinquent adolescent group had higher scores in all
items of the WCST as compared with the control group.
Conclusion and recommendations
Male delinquents were more violent in their acts.
Financial stress factors were higher in boys, whereas girls
were exposed to sexual abuse as well.
Substance abuse was a dominant feature in both (nicotine
smoking and polysubstance abuse). Girls had significantly
higher scores on the adjustment disorder, identity disorder,
depression, bulimia, and sleep disorders.
Girls were significantly hostile in all different aspects of
hostility (overt, self-criticism, other’s criticism, paranoid
aggression, guilt feelings, and the total score). Personality
characteristics showed no significant difference in any of
the subscales: extraversion, neuroticism, psychoticism,
and psychopathic deviation.
Girls had lower IQ, verbal, and performance scores.
Vocabulary, arithmetic, digit span, digit symbol, and block
design scales of the WAIS were lower in girls. No
significant difference was observed between boys and
girls in the WCST in any of the subscales. Management
plans and rehabilitation programs for adolescents admitted
to correctional institutes should be tailored according to
each individual’s circumstances, symptoms, abilities, and
personality characteristics, and sex appropriate treatment
should be focused upon and not according to general
concepts and predetermined ideas.
Acknowledgements
There are no conflicts of interest.
References
Abdou AA (2005). Psychiatric assessment of juvenile delinquents admitted in
correctional institutes in Egypt: correlation between psychiatric morbidity:
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Abou Nahia SE (1989). Eysenck personality questionnaire, Arabic version. Cairo:
Dar El Nahda El Massria.
Abram KM, Choe JY, Washburn JJ, Teplin LA, King DC, Dulcan MK (2008).
Suicidal ideation and behaviors among youths in juvenile detention. J Am
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Original article 15
The role of the brain-derived neurotrophic factors
in the progression of bipolar disorders
Heba Fathya, Shereen Mohamed Abd El-Mawellaa, Hoda Abdoua
and Amal Abdoub
Departments of aPsychiatry and
b
Clinical and Chemical Pathology, Faculty of Medicine,
Cairo University, Cairo, Egypt
Correspondence to Heba Fathy, Department of
Psychiatry, Faculty of Medicine, Cairo University,
Cairo, Egypt
Tel: + 20 101 404 826;
Received 11 August 2011
Accepted 5 October 2011
Introduction
Bipolar disorder (BPD) is considered to be the most prevalent psychiatric
conditions, and is also among the most severe and debilitating. It was suggested
that the brain-derived neurotrophic factor (BDNF) plays an important role in the
pathophysiology of mood disorders. BDNF appears to be an unspecific
biomarker of neuropsychiatric disorders characterized by neurodegenerative changes.
Aim
The aim of the study was to investigate the association between BDNFs and
progression of BPDs.
After receiving approval from the ethical committee in kasr El Eini hospital,
80 participants were randomly selected in a comparative cross sectional study.
The sample consisted of two groups: a group of patients with BPDs (n = 40),
including patients with manic, depressive, mixed episode, or in remission, and a
control group (n = 40). The patients were recruited from the psychiatric outpatient
clinic. Patients were diagnosed by a lecturer of psychiatry according to the
Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria.
Psychometric procedure: the Hamilton rating scale of depression and the
Young Mania Rating Scale were used: laboratory: Radio-immune assay of
BDNFs was carried out.
Results
Fifty-five percent of the patients in the bipolar group had three or more episodes. There
was a statistically significant difference between the cases and the controls in the level
of BDNF. There was a negative correlation between the BDNF and the number of
episodes (P = 0.000) and there was also a negative correlation between BDNF and
disease duration (P = 0.000). There were no correlations between BDNF and the
diagnosis of BPD (P = 0.3).
Conclusion
BDNF was lower than normal in bipolar patients and this was correlated with the
number of episodes and duration of disease.
Keywords:
brain-derived neurotrophic factor, bipolar disorder, number of episodes
1110-1105
Introduction
Mood disorders, such as major depressive disorder
(MDD) and bipolar disorder (BPD), are the most
prevalent psychiatric conditions, and are also among the
most severe and debilitating. However, the precise
neurobiology underlying these disorders is currently
unknown. One way to combat these disorders is to
discover novel biomarkers for them. The development
of such biomarkers will aid both in the diagnosis of
mood disorders and in the development of effective
psychiatric medications to treat them. A number of
preclinical studies have suggested that the brain-derived
neurotrophic factor (BDNF) plays an important role in
the pathophysiology of mood disorders (Hashimoto,
2010).
BD has a poorer longer-term outcome than previously
thought, with persistent cognitive impairment and functional decline. The neurobiological underpinnings that
might underlie these changes remain unknown. Changes in
the levels of BDNF and cytokines may be potentially
responsible and BDNF was decreased only in those
patients in the late stage of BPD. Moreover, when the
levels were compared between patients at early and late
stages of illness, there was a significant decrease in BDNF
and IL-6 in the later stage of BD compared with the early
stage and hence BDNFand continued elevations in cytokines;
thus, these may have the potential to serve as markers of
illness progression in BD (Kauer-Sant0 Anna et al., 2009).
BPD follows a staged trajectory in which persistence of
illness is associated with a number of clinical features
DOI: 10.7123/01.EJP.0000411123.49083.e0
such as progressive shortening of the interepisode interval
and decreased probability of treatment response. The biochemical foundation of this process appears to incorporate
changes in inflammatory cytokines, cortisone, neurotrophins,
and oxidative stress. There is a growing body of evidence to
suggest that these markers may differ between the early and
late stages of the disorder. The presence of a series of
tangible targets raises the spectra of development of rational
neuroprotective strategies, involving judicious use of current
therapies and novel agents. Most of the currently used mood
stabilizers exert effects on oxidative stress and neurotrophins, while novel potentially neuroprotective agents are
being developed. These developments need to be combined
with service initiatives to maximize the opportunities for
early diagnosis and intervention (Berker et al., 2010).
Aim
This study was conducted to examine the associations
between BDNFs and progression of BPDs.
After receiving consent from the ethical committee in Kasr
El Eini hospital, and written informed consent, 80 participants were randomly selected in a comparative cross
sectional study. The sample consisted of two groups: a group
of patients with BPDs (n = 40), including patients with
manic, depressive, mixed episode, or in remission, and a
control group (n = 40). The patients were recruited from
Kasr Al Aini psychiatric hospital (outpatient’s clinic, inpatient department). The control group was recruited from
among relatives of patients attending Kasr Al Aini outpatient’s clinic. This was done over 6 months. Patients were
diagnosed by a lecturer of psychiatry according to the
Diagnostic and Statistical Manual of Mental Disorders, fourth
edition (DSM-IV) (APA, 1994) criteria. Both sexes were
included and the age limit was 20–50 years. We excluded
patients with other psychiatric disorders, mental retardation,
organic mental disorders, and substance-induced psychiatric
disorders. We compared patients with few episodes with
patients with several episodes and compared both with the
control group. The diagnosis of BPD in remission was
established according to three factors: syndromal (DSM-IV
criteria for disorder no longer met), symptomatic (Young
Mania Rating Scale score r5 and Hamilton Depression
Rating Scale score r8), and functional (regaining of premorbid occupational and residential status). These ratings
were carried out according to Tohen et al. (2003).
Tools
Semistructural interview
A specially designed semistructural interview derived
from the Kasr El Aini psychiatric sheet was used to cover
demographic data, personal data, past history, and family
history.
The structured clinical interview for the DSM Axis of disorders
The structured clinical interview for DSM-IV Axis I
disorders provides broad coverage of Axis I psychiatric
diagnosis according to DSM-IV (First et al., 1997).
Hamilton Depression Rating Scale
This scale was formulated by Hamilton (1960, 1967).
The original version consisted of 17 items and was later
increased to 24 items by Klerman et al. (1985). The scale
is not meant to be a diagnostic instrument (Preskorn
and Fast, 1993). Hamilton Depression Rating Scale was
found to distinguish between different groups of patients
drawn from general practice, day-patient care, and
inpatients (Carrol et al., 1973). The concurrent validity
is high (Kearns et al., 1982). The interrater reliability of
Hamilton Depression Rating Scale is also consistently
high (Hamilton, 1960).
Young Mania Rating Scale
The Young Mania Rating Scale was developed in 1978,
and the interrater reliability for the scale is high (Young
et al., 1978). The choice of items was made on the basis of
published descriptions of the core symptoms of the manic
phase of BPD and includes abnormalities that exist over
the entire range of illness, from mild to severe.
Depressive symptoms are not assessed. The severity
rating for each of 11 items is based on the patient’s
subjective report of his or her condition over the previous
48 h and on the clinician’s behavioral interview, with an
emphasis on the clinician’s observations. There are four
items that are graded on a 0–8 scale (irritability, speech,
thought content, and disruptive/aggressive behavior),
whereas the remaining seven items are graded on a 0–4
scale. These four items are given twice the weight of the
others to compensate for poor cooperation from severely
ill patients.
Laboratory
The radioimmune assay technique using the Quantikine
human BDNF Immunoassay, which is a 3.5 h solid phase
enzyme-linked immunosorbent assay designed to measure human BDNF in cell culture supernates, serum, and
plasma, was used. It contains recombinant human BDNF
expressed in Sf 21 cells and antibodies raised against the
recombinant factor. This immunoassay has been shown to
quantify the recombinant BDNF accurately. These
results indicate that the Quantikine kit can be used to
determine the relative mass values for natural human
BDNF (R&D Systems Inc., Minneapolis, MN, USA).
The statistical methods
Data were statistically described in terms of mean ± SD,
frequencies (number of cases), and percentages when
appropriate. Comparison of age between the study groups
was carried out using the Student t-test for independent
samples. For comparing categorical data, the w2-test was
performed. An exact test was used when the expected
frequency was less than 5. Correlation between various
variables was assessed using the Spearman rank correlation equation for nonnormal variables. P-values less
than 0.05 were considered statistically significant. All
statistical calculations were performed using computer
programs Microsoft Excel 2007 (Microsoft Corporation,
New York, USA) and Statistical Package for the Social
Science (SPSS; SPSS Inc., Chicago, Illinois, USA) version
15 for Microsoft Windows.
Role of the brain-derived neurotrophic factors Fathy et al. 17
Results
52.5% of the sample comprised men and 47.5% were
women. Both groups were matched for age. Sixty five
percent of the patients showed bipolar manic (Table 1).
Fifty five percent of patients had more than three episodes
(Table 2). There was a negative correlation between the
BDNF and number of episodes (P = 0.000) (correlation
coefficient = – 0.636) and there was also a negative correlation between BDNF and disease duration (P = 0.000)
(correlation coefficient = – 0.666). There was no correlation
between BDNF and the diagnosis of BPD (P = 0.3).
Discussion
BDNF is the most widely distributed neurotrophin in the
central nervous system, where it plays several pivotal roles
in synaptic plasticity and neuronal survival. As a consequence, BDNF has become a key target in the pathophysiology of several neurological and psychiatric diseases.
Recent studies have consistently reported altered levels of
BDNF in the circulation (i.e. serum or plasma) of patients
with major depression, BPD, Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. Correlations between
serum BDNF levels and affective, cognitive, and motor
symptoms have also been described. BDNF appears to be
an unspecific biomarker of neuropsychiatric disorders
characterized by neurodegenerative changes (Teixeira
et al., 2010). The aim of this study is to detect the
differences in the levels of BDNF in bipolar patients and
healthy controls and to detect the relation between the
number of the episodes (disease progression) and the
serum level of BDNF in patients with BPD.
We found significant differences between patients with
BPD and healthy controls as regards the level of serum
BDNF as 40% of the patients had a low serum level of
BDNF versus 15% only of the healthy controls (Table 3).
Also, we found that there was a negative correlation between the level of the BDNF and the number of episodes
of BPD. There was also a negative correlation between
the serum level of BDNF and the duration of illness.
The above result is supported by recent data, which
suggest that changes in neuroplasticity, cell resilience,
and connectivity are the main neuropathological findings
in BD. Data from differential lines of research converge to
BDNF as an important contributor to the neuroplasticity
changes described among BD patients. BDNF has also
been shown to decrease as the disorder progresses. These
findings suggest that BDNF plays a central role in the
progression of BD (Grande et al., 2010).
Grande et al. (2010) also found that BDNF serum levels
have been shown to be decreased in depressive and manic
episodes, returning to normal levels in euthymia. But in
our study we did not obtain this finding, perhaps due to
the small sample in our study.
In addition, our study is in concordance with the study carried
out by Kauer-Sant0 Anna et al. (2009) to examine BDNF levels
and their relationship in BD patients in the early and late
stages of the disorder. BDNF was decreased only in those
patients in the late stage of BPD. Moreover, BDNF levels
were negatively correlated with the length of illness. When
the levels were compared between patients at early and
late stages of illness, there was a significant decrease in
BDNF in the later stage of BD compared with the early stage.
Also, Machado-Vieira et al. (2007) investigated whether
BDNF levels are altered during mania. Sixty participants
(14 men and 46 women) were selected and included in the
study. Thirty patients meeting the structured clinical
interview for DSM-IV Axis I criteria for manic episodes
were age and sex matched with 30 healthy controls. They
found that the mean BDNF levels were significantly
decreased in drug-free/naive patients compared with
healthy controls. Severity of the manic episode presented
a significantly negative correlation to plasma BDNF levels.
In contrast to our results (Table 4) are those obtained
by Dias et al. (2009), who measured serum BDNF levels
using an enzyme-linked immunosorbent assay method in
65 euthymic type I BD patients and 50 healthy controls
and found no significant differences in serum BDNF
levels in BD patients and healthy controls. They found
significant positive associations between serum BDNF
levels and illness duration, and manic and depressive
episodes only in female BD patients. This difference can
be explained by the fact that the patients were in the
euthymic stage, but in our study, there were patients with
different diagnosis (manic, depressive, euthymic).
As regards the relation between the BDNF and sex
differences, 52.5% of the sample comprised men and
47.5% comprised women, both matched for age. The
Table 3 Level of brain-derived neurotrophic factor
Cases
Control
Number (%)
Number (%)
P
24 (60)
16 (40)
34 (85)
6 (15)
0.01
Table 1 Different diagnoses of the bipolar group
Bipolar
Bipolar
Bipolar
Bipolar
depression
manic
mixed
in remission
Number
Percentage
1
26
2
11
2.5
65
5
27.5
Within range
Low
Table 4 Sex differences in the level of brain-derived neurotrophic factor
Table 2 Number of episodes
o3
Z3
Number
Percentage
18
22
45
55
Within range
Low
Males
Females
Number (%)
Number (%)
13 (61.9)
8 (38.1)
11 (57.9)
8 (42.1)
P
0.7
results show no significant differences between male and
female patients. This is also in contrast to the study
carried out by Dias et al. (2009).
One of the limitations of this study will be the effect of
drug taking by the patients. As all patients in our study
were taking drugs, the possible question is that whether
the drugs affect the level of BDNF. A study was carried
out by De Oliveira et al. (2009), who examined the effect
of the medication on the level of BDNF in BPD. BDNF
serum levels were assessed using enzyme-linked immunosorbent assay. Serum BDNF levels in drug-free and
medicated BD patients were decreased when compared
with controls. The BDNF levels did not differ between
medicated and drug-free BD patients. When analyzing
patients according to mood states, serum BDNF levels
were lower in BD patients during both manic and
depressive episodes as compared with healthy controls.
Results suggest that the association of lower serum
BDNF and BD mood episodes is maintained even in
medicated patients, which strengthens the notion that
BDNF serum levels may be considered a biomarker of
mood episodes.
The change in the level of neurotrophic factors in patients
with BPD may be a new challenge in the treatment of
mood disorders. Most of the currently used mood stabilizers
exert effects on oxidative stress and neurotrophins, while
novel potentially neuroprotective agents are being developed. These developments need to be combined with
service initiatives to maximize the opportunities for early
diagnosis and intervention (Berk et al., 2010).
Acknowledgements
References
American Psychiatric Association (APA). Diagnostic and statistical manual of
mental disorders. 4th ed. VA, USA: American Psychiatric Publ; 2000.
Berk M, Conus P, Kapczinski F, Andreazza AC, Yücel M, Wood SJ, et al. (2010).
From neuroprogression to neuroprotection: implications for clinical care. Med
J Aust 193:S36–S40.
Carroll BJ, Fielding JM, Blashki TG (1973). Depression rating scales. A critical
review. Arch Gen Psychiatry 28:361–366.
De Oliveira GS, Ceresér KM, Fernandes BS, Kauer-Sant’Anna M, Fries GR,
Stertz L (2009). Decreased brain-derived neurotrophic factor in medicated
and drug-free bipolar patients. J Psychiatr Res 43:1171–1174.
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Cognitive function and serum levels of brain-derived neurotrophic factor in
patients with bipolar disorder. Bipolar Disord 11:663–671.
First MB, Spitzer RL, Gibbon M, Williams JBW (1997). Structured clinical interview for DSM-IV Axis I Disorders (SCID-I). VA, USA: American Psychiatric
Publishing, Inc; 1997.
Grande I, Fries GR, Kunz M, Kapczinski F (2010). The role of BDNF as a mediator
of neuroplasticity in bipolar disorder. Psychiatry Invest 7:243–250.
Hamilton M (1960). A rating scale for depression. J Neurol Neurosurg Psychiatry
23:56–62.
Hamilton M (1967). Development of a rating scale for primary depressive illness.
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et al. (2009). Brain-derived neurotrophic factor and inflammatory markers in
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et al. (2007). Decreased plasma brain derived neurotrophic factor levels in unmedicated bipolar patients during manic episode. Biol Psychiatry 61:142–144.
Preskorn SH, Fast GA (1993). Beyond signs and symptoms: the case against a mixed
anxiety and depression category. J Clin Psychiatry 54:24S–32S.
Teixeira AL, Barbosa IG, Diniz BS, Kummer A (2010). Circulating levels of brainderived neurotrophic factor: correlation with mood, cognition and motor
function. Biomarkers Med 4:871–887.
Tohen M, Zarate CA. Jr, Hennen J, Khalsa HMK, Strakowski SM, Gebre-Medhin P,
et al. (2003). The McLean-Harvard first-episode mania study: prediction of
recovery and first recurrence. Am J Psychiatry 160:2099–2107.
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reliability, validity and sensitivity. Br J Psychiatry 133:429–435.
Original article 19
Depression and Alzheimer disease: a risk factor or a prodrome
Hoda Salama, Tarek Molokhia, Hazem Maarouf and Hesham Sheshtawy
Department of Neuropsychiatry, Faculty of Medicine,
Alexandria University, Alexandria, Egypt
Correspondence to Tarek Kamal Molokhia,
Department of Neuropsychiatry, Faculty of Medicine,
Alexandria University, Alexandria, Egypt
Tel: + 01223173572;
Background
The number of elderly individuals in the population is steadily increasing. One of the
well known problems in the elderly is cognitive impairment. Alzheimer disease is the
most common cause of cognitive impairment. Another health problem in this age group
that can present with cognitive impairment is depression. Several controversies exist
regarding the relationship between depression and Alzheimer disease.
Aim
This work aims at studying whether depression can be a risk factor for future
development of Alzheimer disease.
Patients and methods
Twenty patients with Alzheimer disease in the outpatient clinic were asked about their
history of depression and the presence of depression at the onset of illness.
Results
One unmarried woman (5%) had a history of depression. Seven patients (35%) had
depression at the onset of illness.
Conclusion
The current study supports the hypothesis that depressed mood is not a risk factor for
future development of Alzheimer disease. Further studies are needed to assess the
relationship between cognitive symptoms of depression and future development of
Alzheimer disease.
Keywords:
Alzheimer disease risk factor, depression, prodrome
1110-1105
Introduction
The number of elderly people in the population is
steadily increasing. In 1900, the percentage of elderly
individuals older than 65 years was 5%. In 2003, the
percentage increased to 15%, and it is expected to be
about 24% in 2030. Elderly individuals suffer from several
social and medical problems. One of the most common
medical problems suffered by them and faced by
physicians dealing with them is cognitive decline
(Steffens et al., 2009).
One of the most well-known causes of progressive
cognitive decline in the elderly is dementia. Dementia
has a serious impact on the affected person, his/her
caregiver(s), and on the community as a whole. The most
common cause for dementia is Alzheimer disease (AD).
Five percent of elderly individuals above 65 years suffer
from AD. This percentage increases to 30% in those
above 85 years. It is expected that 81 million people will
suffer from AD in 2040 (Alzheimer’s Association, 2009).
Anticholinesterases were introduced as a pharmacological
treatment for dementia with an evidenced efficacy in
delaying the progress and sometimes improving the course
of the disease (Dickerson et al., 2007; Traykov et al.,
2007; Wu et al., 2009). Therefore, early detection and
treatment of dementia is of considerable importance
(Milisen et al., 2006; Belleville et al., 2008). This has led
to the recognition of mild cognitive impairment (MCI)
(Dierckx et al., 2007). MCI is the intervening zone between
normal aging and dementia. MCI is considered by many
authors as the prodrome of dementia (Brodaty et al., 2003;
Rosenberg and Lyketsos, 2008; Werner and Korczyn, 2008).
There are several causes for cognitive decline in the
elderly other than dementia. Examples for these causes
are systemic illness, previous psychotic illness, intake of
medications, and depression (Steffens et al., 2009).
Depression is a very common problem among the elderly
population. Prevalence of clinically significant depression
among them is about 10%, which means that depression
is more common than dementia (Potter and Steffens
et al., 2007; Hattori, 2008, 2009). Depression and
dementia have serious consequences; yet, their treatment
and prognosis are totally different. Therefore, differentiation between depression and dementia is of considerable
importance (Chertkow et al., 2008; Steffens, 2008; Thomas
and O’Brien, 2008).
In the real clinical practice, this differentiation is
sometimes very difficult. This difficulty is due to the
following reasons:
(1) Cognitive decline is a common presentation for depression in the elderly (known as pseudodementia).
(2) Depressive symptoms are common in actual dementia.
(3) Sometimes, depression is the prodrome of dementia.
DOI: 10.7123/01.EJP.0000411507.77863.13
Treating depression with antidepressants markedly improves cognitive decline, but the cognition rarely
becomes normalized (Wright and Persad, 2007; Gagliardi,
2008; Steffens and Potter, 2008).
Only one female patient (5%) reported a history of
depression (Fig. 2). Of the 20 patients, seven (35%)
reported suffering from depression at the onset of illness
(Fig. 3).
The question now is can we consider depression as a risk
factor for future development of AD?
Discussion
Aim
This work aims at studying whether depression can be a
risk factor for future development of AD.
Patients
This study included 20 patients with AD in the
outpatient clinic. They were chosen according to the
following inclusion and exclusion criteria:
Is depression a risk factor for developing future dementia
(including AD) or is depression a prodrome of AD?
Figure 1
recent
amnesia
20%
agitation
20%
agitation
sleep
Inclusion criterion:
sleep
15%
(1) Age above 60 years.
Exclusion criteria:
(1) Presence of previous psychotic illness.
(2) Mental subnormality.
(3) Presence of severe systemic illness (e.g. chronic
advanced liver disease, chronic advanced renal disease).
(4) Presence of previous neurological disease (e.g. stroke,
infection, and epilepsy).
agitation & sleep
recent amnesia
agitation &
sleep
45%
First symptom for seeking medical advice.
Figure 2
positive
5%
Methods
Written consent was taken from the patients (or their
relatives) before participation in the study.
positive
Clinical assessment was performed with special emphasis
on the following:
(1)
(2)
(3)
(4)
(5)
negative
Age.
Sex.
Main presenting manifestations.
Previous history of depression.
Depression at onset of illness.
negative
95%
History of depression.
Results
Figure 3
The present study was carried on 20 patients with AD.
The number of women was 12 (60%), whereas the
number of men was eight (40%). The mean age of the
studied group (in years) was 79.65 ± 3.13.
Recent amnesia was the first symptom that propelled the
caregivers of the patient to seek medical advice in four
cases (20%), whereas agitation alone was responsible for
another four cases (20%) to start to seek medical advice;
sleep problems alone were responsible for three cases.
The majority (nine cases; 45%) sought medical advice for
both agitation and sleep problems (Fig. 1).
positive
35%
positive
negative
negative
65%
Depression at onset of disease.
Depression and Alzheimer disease Salama et al. 21
Answering this question is important because if depression is a risk factor for AD, effective treatment of
depression can, theoretically, decrease the probability of
developing AD in the future.
The number of women in the studied group was 12
(60%), whereas the number of men was eight (40%). The
mean age was 79.65 ± 3.13 years. These findings were
consistent with that of Benson et al. (2005).
According to the current study on AD patients, only one
unmarried woman (5%) reported a history of depression
(Fig. 2). Also, in this group, seven patients (35%)
reported suffering from depression at the onset of illness
(Fig. 3). These findings support the fact that depression
is not a risk factor for AD. Also, these findings support the
theory of considering depression as a prodrome of
AD under some, but not all, conditions. Accordingly, we
can see cases of depression alone, cases of depression
at the start that culminate in AD, and finally we can
see AD that did not start from depression. Thus, we can
see depression and dementia from a dimensional
perspective.
Several cross-sectional and longitudinal epidemiological
studies have found an association between late-life
depressive symptoms and subsequent cognitive decline,
including MCI and probable dementia (Barnes, et al.,
2006; Geda et al., 2006), but it remains uncertain whether
the presence of depressive symptoms is a risk factor or
a prodrome or a consequence of a pathological cognitive
decline or a part of the pathological process.
A meta-analysis (Ownby et al., 2006) has suggested that a
history of depression approximately doubles the risk of
developing AD, supporting the fact that depression can
indicate a risk of future occurrence of AD. However,
recent large prospective cohort studies (Panza et al.,
2008a, 2008b; Becker et al., 2009) have failed to show that
depressed mood is a risk factor for MCI and dementia.
In the Baltimore Longitudinal Study of Aging and the
Personnes Agée QUID study, the presence of premorbid
depressive symptoms increased the risk of later development of dementia, especially AD, but only in men,
suggesting a predisposition based on sex (Fuhrer et al.,
2003; Dal Forno et al., 2005). This was also reported in the
Framingham Heart study (Saczynski et al., 2010).
In The Women’s Health Initiative Memory Study
(WHIMS) (Goveas et al., 2011), a cohort of postmenopausal women aged 65–79 years at study baseline who
met the screening cutoff for depressive disorder, a greater
risk of subsequent MCI and incident dementia was found
after a mean follow-up of 5.4 years than in those who were
not depressed. These findings remained significant after
adjusting for multiple potential confounding variables,
including demographic characteristics, lifestyle variables,
cardiovascular risk factors, presence of cerebrovascular
disease, antidepressant use, baseline cognitive function
[as measured using the modified mini-mental state
examination (3Ms)], and prior use and current prescription of hormone therapy. The participants who were
depressed had approximately twice the hazard of developing MCI and probable dementia.
Benson et al. (2005) compared the performance of the
mini-mental state examination (MMSE) total score and
item scores in separating four groups of elderly (55–85
years of age) individuals: normal controls, patients with
MCI, patients with mild AD, and patients with depression. They concluded that the MMSE effectively
separates those with mild AD from the other three
groups and MCI from normal aging, but it is relatively
ineffective in separating normal elderly individuals from
those with depression and individuals with MCI from
those with depression. Measures other than the MMSE
may need to be implemented to evaluate the mental
status to more effectively separate MCI from depression
and depression from normal aging. Was the use of 3Ms an
effective choice for adjusting the confounding factor of
baseline cognitive function in WHIMS? It is a question
that needs further research.
Accordingly, the findings of the current study were
consistent with that of the Italian Longitudinal study
on Aging and the study by Becker and colleagues. In
contrast, these findings were inconsistent with that of the
Baltimore Longitudinal Study of Aging, the Personnes
Agée QUID study, and WHIMS.
This is not a prospective study. Therefore, we cannot
ignore the recall bias factor with regard to the history of
depression. In contrast, answering ‘yes’ to the question of
‘did you (your parent) have a past history of depression?’
usually denotes the presence of previous depressed mood
rather than a full-blown picture of depressive disorder.
Accordingly, we can observe that studies that comment
on depressed mood [Italian Longitudinal study on Aging,
Becker et al. (2009), and the current study] did not find
any relation with future development of dementia. In
contrast, studies that commented on depressive symptoms (Baltimore Longitudinal Study of Aging, the
Personnes Agée QUID study, and WHIMS) found a
positive relation with future development of dementia. It
seems that the presence of memory symptoms of
depressive disorder is a risk for development of future
dementia rather than just the presence of depressed
mood. In contrast, because the neurodegenerative
changes seen in AD precede the clinical diagnosis by
several years, these memory symptoms of depressive
disorder may be the earliest manifestation of this
neurodegenerative disease, suggesting that depressive
disorder with memory symptoms was actually a prodrome
of AD. This hypothesis needs to be further studied.
Acknowledgements
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Original article 23
Gender-related phenomenological and neuropsychological
differences in elderly patients with depression
Fatma Moussaa, Mohamed Nasreldia, Hani Hamedb and Amany Ahmed Abdoua
a
Department of Psychiatry, Faculty of Medicine, Cairo
University, Cairo and bDepartment of Psychiatry,
Faculty of Medicine, Beni Suief University, Beni Suief,
Egypt
Correspondence to Mohamed Nasreldin, MD,
Assistant Professor of Psychiatry, Department of
Psychiatry, Faculty of Medicine, Cairo University,
Cairo, Egypt
Tel: + 225318885; fax: + 233386951;
Aim
The objectives of this work were to detect phenomenological sex-specific differences
in elderly patients with depression for better understanding and to illustrate
neuropsychological sex-specific differences in elderly patients with depression for
better management.
Subjects
A comparative study with consecutive samples. Two groups were compared in the
study comprising 40 elderly patients of both sexes with depression: 20 depressed
men and 20 depressed women aged 60 years or above. They were recruited from the
psychiatry outpatient clinic of Kasr Al Aini hospital with no obvious cognitive
impairment or substance-related psychiatric disorders.
Methods
Diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth
edition, Symptom Checklist-90, mini-mental state examination (MMSE), Geriatric
Depression Scale (GDS), Wechsler Adult Intelligence Scale, and State–Trait Anxiety
Inventory were used.
Results
A comparison between the depressed male and female subgroups revealed that the
characteristics of the patients were similar in both sexes except for some significant
findings; for example, depression in elderly women is more associated with
widowhood, more suffering from a sense of worthlessness, lack of attention, and more
disturbance in reasoning and constructional abilities. However, elderly men reported
more sexual dysfunction and a significant negative correlation between memory
impairment (MMSE) and severity of depression (GDS).
Conclusion
There were no sex-specific differences in elderly depressed patients except that
depression in elderly women was more associated with widowhood, a sense of
worthlessness, lack of attention, and more disturbance in reasoning and constructional
abilities, whereas elderly men reported more sexual dysfunction and a significant
negative correlation between memory impairment (MMSE) and severity of depression
(GDS).
Keywords:
depression, elderly, sex, sex-specific differences
1110-1105
Introduction
Worldwide, life expectancy is increasing. Currently, about
10% of the world’s population comprises older adults
(aged 65 and above). For mental health, this implies an
increase not only in the neurodegeneration conditions,
such as Alzheimer’s dementia, but also in depressive
disorders (Baldwin, 1997).
It has been predicted that there will be a total of
two billion people over the age of 60 in 2050; 80% of them
will be living in developing countries (Pinto Meza et al.,
2006).
In Egypt, over the past five decades, life expectancy at
birth has increased globally by almost 20 years, from 42.4
in 1950–1955 to 68.3 years in 2000–2005. It is also
projected that by 2025, it will reach 77.8 years [World
Health Organization (WHO), 2006].
Epidemiologic studies have found depression to be more
common in women, although this sex-specific difference
is less pronounced in older adults (Blazer, 2003). The
study also found that women have higher incidence rates
of major depressive disorder and a more chronic course
(Essau et al., 2010).
Nearly twice as many women as men suffer from major
depressive disorders. This difference continues into
extreme old age, but the differential decreases. The
higher prevalence of depression among women is due to a
higher risk of first onset rather than differential
persistence or recurrence. The cause of the sex-specific
DOI: 10.7123/01.EJP.0000411115.10146.c9
difference in rates is not known, but speculation covers
cognitive styles, psychosocial and economic stress, an
increased rate of abuse during childhood and in the work
place, an increase in the incidence of hypothyroidism, and
other biological factors related to the effects of endogenous and exogenous gonadal steroids (there is no sexspecific difference in incidence before adolescence).
However, these differences pertain only to unipolar
depression (Kessler, 2003).
criteria of organic mood disorder; all patients who fulfilled
the DSM-IV criteria of substance-induced mood disorder
or psychotic disorder with predominantly depressive
symptoms; agitated and suicidal patients; and individuals
who refused to participate in the study.
Depressed men have significantly lower disclosure rates
of depressive symptoms and treatment and more negative
attitudes toward help-seeking for mental health problems
than do women (O’Connor et al., 2001; Addis and
Mahalik, 2003; Kalache, 2006).
The modified Kasr Al Aini Geriatric sheet
Men were significantly less likely than women to endorse
depressive symptoms such as feeling depressed or low
(39% men vs. 47% women) and having lost interest or
pleasure in things they usually enjoy (37% men vs. 42%
women). Men were also less likely than women to report
fatigue (62% men vs. 67% women). Men were significantly more likely to be married, less likely to have two or
more previous depression episodes, and reported lower
overall depression severity (Hinton et al., 2006).
Methods
This study is a comparative cross-sectional study; all
patients were subjected to the following:
The depressed group was classified according to the
criteria of the DSM-IV into patients with major
depressive disorder and those with nonmajor depressive
disorder (adjustment disorder with depressed mood,
dysthymic disorder, and minor depressive disorder).
Symptom Checklist-90 (El Behery, 1984): Arabic version
The Symptom Checklist (SCL)-90 is a self-reporting,
clinical symptom rating scale consisting of 90 questions. It
is designed for use on psychiatric outpatients. Responses
indicate symptoms associated with nine psychiatric constructs (somatization, obsessive compulsive disorder, interpersonal sensitivity, depression, anxiety, hostility, phobic
anxiety, paranoid ideation, and psychoticism).
Geriatric Depression Scale (Baza, 1997): Arabic version
Aim
The objectives of this work were to detect phenomenological sex-specific differences in elderly patients with
depression for better understanding and to illustrate
neuropsychological sex-specific differences in elderly
patients with depression for better management.
Subjects and methods
This is a self-rated 30-item scale used to rate depression
in the elderly. The Geriatric Depression Scale (GDS) has
also been recommended by the Royal College of
physicians, British Geriatric society, as a suitable method
for screening of depression in the geriatric age group and
rating its severity. In our study, the GDS was chosen as it
is more specific for the elderly. It was used as a screening
method for detection of depressed patients, and it was
also used as a measure of the severity of depression in
these patients.
Subjects
This study was designed as an outpatient cross-sectional
comparative study after obtaining approval from the
ethical research committee that conforms to the provisions of the world medical association’s Declaration of
Helsinki. The study consisted of 40 individuals who were
selected on consecutive referral basis recruited from the
geriatric psychiatry outpatient clinic in Kasr Al Aini
university hospitals from July to December 2008 according to the inclusion criteria. They were all elderly
outpatients of both sexes (60 years and above). All
individuals included in this study fulfilled the general
inclusion and exclusion criteria. All patients gave consent
to participate in the study after a full explanation of
procedures was provided. The sample was divided into
two groups. Group A (the depressed group) consisted of
40 patients diagnosed to have a clinically recognizable
depression and subdivided into two subgroups: depressed
men (N = 20) and depressed women (N = 20). All
patients fulfilled the Diagnostic and Statistical Manual of
Mental Disorders, fourth edition (DSM-IV) criteria of a
depressive disorder. Exclusion criteria included the
following: patients with dementia and other organic
mental disorders; all patients who fulfilled the DSM-IV
State–Trait Anxiety Inventory (El Behery, 2005): Arabic version
It includes two self-rated scales: State Anxiety and Trait
Anxiety. Trait Anxiety consists of 20 items that describe
the individual feelings generally, whereas State Anxiety
consists of 20 items that describe the individual feelings
at a particular moment.
Mini-mental state examination (Molloy et al., 1991): Arabic
version
The mini-mental state examination (MMSE) is probably
the most widely used measure of cognitive decline. The
MMSE has been suggested in early diagnosis of
Alzheimer’s disease. The MMSE has a maximum score
of 30 points, with different domains including orientation, registration, attention, calculation, recall, language,
and visual concentration.
The Wechsler Adult Intelligence Scale (Meleka and Ismail,
1996): Arabic version
It is a general test of intellegence (IQ) published in 1955
as a revision of the Wechsler Bellevue test 1939. The fullscale IQ test is broken down into 14 subtests, comprising
seven verbal subtests (information, comprehension,
Gender-related differences in elderly patients Moussa et al. 25
arithmetic, similarities, vocabulary, digit span, and letter
and number sequencing) and seven performance subtests
(picture completion, digit symbol, block design, matrix
reasoning, picture arrangement, symbol search, and object
assembly). The Wechsler Adult Intelligence Scale
(WAIS) is appropriate through adulthood and for use in
individuals over 74 years of age.
Statistical analysis
All data from both groups were computed and analyzed
using the Statistical Package for Social Sciences (SPSS
version 15, IBM, Armonk, New York, USA) software for
statistical analysis. Descriptive statistics was used for
illustrating the mean and SD of quantitative data.
Statistical tests were used to ascertain the significant
differences between the two groups and sex-specific
differences in the depressed group. The Student t-test
was used for quantitative variables, for example, age and
MMSE, WAIS, GDS, and SCL scores. The Chi-square
test was used for qualitative variables, for example, sex,
education, occupation, marital status, socioeconomic
level, depressive symptoms, and severity of depression.
A probability level of Po0.05 was considered statistically
significant (Levesque, 2007).
Results
Comparison between men and women in the depressed
group
Sociodemographic Data
There was no significant difference between depressed
men and women with respect to age (P = 0.07),
education (P = 1), occupation (P = 0.07), socioeconomic
level (P = 0.15), or caregiver support (P = 0.55). However, there was significant difference between them with
regard to marital status, which means that there were
more widows among depressed women than there were
widowers among depressed men (P = 0.018).
Table 1 Comparison between depressed men and women with
regard to depressive symptoms
Male (N = 20)
Symptoms
Worthlessness
Anhedonia
Hopelessness
Helplessness
Insomnia
Psychomotor
retardation
Psychomotor
agitation
Fatigue
Poor concentration
Suicidal ideation
Sexual dysfunction
Female (N = 20)
Absent
Present
Absent
Present
No. (%)
No. (%)
No. (%)
No. (%)
16
10
13
11
3
18
(80)
(50)
(65)
(55)
(15)
(90)
15 (75)
3
3
20
14
4
10
7
9
17
2
(20)
(50)
(35)
(45)
(85)
(10)
5 (25)
10
8
13
8
5
20
(50)
(40)
(65)
(40)
(25)
(100)
18 (90)
10
12
7
12
15
0
P
(50)
(60)
(35)
(60)
(75)
(0)
0.05
0.53
1
0.34
0.43
0.15
2 (10)
0.21
(15) 17 (85)
3 (15) 17 (85) 1
(15.8) 17 (84.2) 3 (15.8) 17 (84.2) 0.63
(100) 0 (0)
19 (95)
1 (5)
0.31
(70)
6 (20) 20 (100) 0 (0)
0.04
Po0.05 is significant.
regard to diagnosis of depressive disorders
Male (N = 20) Female (N = 20)
Diagnosis
Major depressive disorder
Dythymic disorder
Adjustment disorder
Minor depressive disorder
Medical comorbidity
Hypertension
Ischemic heart disease
Diabetes mellitus
Asthma
Osteoarthritis
Peptic ulcer
Anemia
Prostatic enlargement
Others (UTI, bronchitis and
hearing difficulties)
No. (%)
No. (%)
P
2
10
4
4
(10)
(50)
(20)
(20)
3
12
4
1
(15)
(60)
(20)
(5)
0.25
8
4
2
0
0
1
0
1
4
(40)
(20)
(10)
(0)
(0)
(5)
(0)
(5)
(20)
10
2
3
1
1
0
1
0
2
(50)
(10)
(15)
(5)
(5)
(0)
(5)
(0)
(10)
0.18
UTI, urinary tract infection.
Clinical Data
Depressive symptoms: Tables 1 and 2.
Psychometric measurement
Tables 3 and 4.
State and Trait Anxiety Scale
Tables 5–7 Depressed women had a significantly higher
sense of worthlessness compared with depressed men.
Also, depressed men reported symptoms of decreased
libido more often than did depressed women; otherwise,
there were no significant differences between depressed
men and women regarding other depressive symptoms
(P = 0.05 and 0.04, respectively). There were no
significant differences between depressed men and
women regarding diagnosis of depressive disorders;
however, the majority of patients were diagnosed with
dysthymic disorder (50% of depressed men and 60% of
depressed women). Of the depressed men, 20% had
adjustment disorder, 20% had minor depressive disorder,
and 10% had major depressive disorder. Of the depressed
women, 20% had adjustment disorder, 15% had major
depressive disorder, and 5% had minor depressive
disorder (P = 0.25). There were no significant differences
between depressed men and women regarding medical
comorbidity (P = 0.18), nor was there any significant
difference between them with regard to SCL subscales.
In addition, there was no significant difference between
depressed men and women with regard to the total score
of the geriatric depressive scale (P = 0.61) or with regard
to the severity of depression according to the geriatric
depressive scale (P = 0.68). There was a significant
difference between depressed men and women regarding
the attention subscale, which reveals an effect of lack of
attention in depressed women more than in depressed
men (P = 0.04). There was no significant difference
between depressed men and women regarding verbal IQ,
performance IQ, and the full scale of WAIS. There was a
significant difference between depressed men and
women regarding Similarities and Block design subscales,
which means that depressed women have a disturbance in
regard to Symptom Checklist, Geriatric Depression scale, and
mini-mental state examination
Male (N = 20)
Mean
Symptom Checklist
Somatization
Obsessions
Interpersonal sensitivity
Depression
Anxiety
Hostility
Phobic anxiety
Paranoid identification
Psychosis
Geriatric Depressive Scale
(GDS)
Mini-mental state examination
Orientation
Registration
Attention
Recall
Naming
Repetition
Comprehension
Reading
Writing
Construction
Total score
SD
Female
(N = 20)
Mean
29.35
21.00
13.2
43.85
22.65
8.10
8.35
7.55
10.40
15.85
12.29
10.36
2.32
14.911
11.170
3.946
2.601
2.212
3.775
4.03
8.9
3
4.4
2.6
2
1
3
0.25
0.25
0.0
25.5
0.5
0.0
0.7
0.5
0.0
0.0
0.0
0.44
0.44
0.0
1.7
regard to the grade of Trait subscale of State–Trait Anxiety
Inventory
SD
Female (N = 20)
No. (%)
No. (%)
P
P
27.2 10.8
26.75 9.7
12.8
1.6
36.70 8.75
23.05 10.18
8.25 3.46
8.95 2.56
6.75 2.63
10.50 2.544
16.5
3.98
0.56
0.08
0.59
0.07
0.91
0.9
0.47
0.31
0.92
0.61
9
3
4
2.7
2
1
3
0.25
0.25
0.1
25.5
0.58
–
0.41
0.52
–
–
–
1
1
0.61
1
0.6
0.0
0.4
0.47
0.0
0.0
0.0
0.44
0.44
0.3
1.7
Male (N = 20)
regard to the severity of depression according to the Geriatric
Depressive Scale
Male (N = 20)
Female (N = 20)
Geriatric Depression Scale
No. (%)
No. (%)
P
Mild
Severe
17 (85)
3 (15)
16 (80)
4 (20)
0.68
reasoning (similarities) and visual perception. There was
no significant difference between depressed men and
women with regard to the grade of WAIS (P = 0.197)
imagination and constructional abilities (Block design)
(P = 0.006 and 0.007, respectively). Depressed men and
women showed no significant difference in the deterioration index of WAIS (P = 0.376). There was no significant
difference between depressed men and women with
regard to the grade of State subscale of STAI (P = 0.175).
The grade of trait and state subscale of STAI showed no
significant difference between depressed men and
women (P = 0.301).
Discussion
Research and clinical evidence revealed that, although
both women and men can develop the standard
symptoms of depression, they often experience depression differently and may have different ways of coping
with the symptoms. Another study reported that elderly
women endorsed depressed mood, anhedonia, and
State Anxiety Scale
None
Mild
Moderate
Severe
Trait Anxiety Scale
None
Mild
Moderate
8
9
1
2
(40)
(45)
(5)
(10)
6
9
5
0
14 (70)
4 (20)
2 (10)
(30)
(45)
(25)
(0)
0.18
14 (70)
6 (30)
0 (0)
0.3
regard to Wechsler Adult Intelligence Scale subscales
Male (N = 20)
Female (N = 20)
WAIS
Mean
SD
Mean
SD
P
Information
Comprehension
Arithmetic
Similarities
Digit span
Vocabularies
Picture arrangement
Picture completion
Block design
Object assembly
Digit symbols
Verbal IQ
Performance IQ
Full scale
8.1
7.5
6.5
3.9
7.95
16.2
4.00
6.95
7.5
8.35
13.75
89.6
99.1
91.2
2.88
1.82
1.67
1.17
2.09
5.58
1.56
2.33
3.56
3.28
7.68
6.86
6.23
6.16
9.25
7.85
6.65
2.65
9.20
17.15
3.85
7.20
4.85
7.80
13.45
90
94.75
88.6
3.8
1.98
1.27
1.5
2.19
4.77
1.35
2.67
2.08
3.87
6.31
7.43
8.8
5.68
0.29
0.56
0.75
0.006
0.07
0.17
0.75
0.75
0.007
0.63
0.89
0.86
0.08
0.17
WAIS, Wechsler Adult Intelligence Scale.
regard to the grade of Wechsler Adult Intelligence Scale
Grade
Average grade
Below average grade
Deterioration
Significant
Nonsignificant
Male (N = 20)
Female (N = 20)
No. (%)
No. (%)
P
10 (50)
10 (50)
6 (30)
14 (70)
0.2
2 (10)
18 (90)
4 (20)
16 (80)
0.38
irritability more often than did men (Steffens et al.,
2000). Women tend to report a greater number of
symptoms and a higher degree of distress and may differ
from men in their perceived need and willingness to seek
treatment (Kornstein et al., 2002). The study results
showed that the majority of patients were diagnosed with
dysthymic disorder (50% of depressed men and 60%
of depressed women). Of depressed women, 15% had
major depressive disorder compared with 10% of
depressed men. The cause of the sex-specific difference
in rates may be related to cognitive styles, psychosocial
stress, and economic stress; yet, the large-sized sample
Gender-related differences in elderly patients Moussa et al. 27
could illustrate a higher difference. These findings
matched with the study that reported that nearly twice
as many elderly women as elderly men suffer from major
depressive disorder (Kessler, 2003; Essau et al., 2010).
Comparison of the depressed female with the depressed
male subgroup revealed a significant difference with
regard to sense of worthlessness, which suggested that
depressed women had lower self-esteem than did
depressed men. This may be understood by the cultural
agreement that women’s self-esteem is dependent upon
their relationships with others; they are less assertive and
lack confidence in controlling their lives, which is
consistent with the study reporting that men may be
more willing to acknowledge fatigue, irritability, loss of
interest in work or hobbies, and sleep disturbances rather
than feelings of sadness, worthlessness, and excessive
guilt (Cochran and Rabinowitz, 2000). Irritability is a
more frequent symptom of depression than depressed
mood, particularly in Arab women, and it is often mild and
takes the form of intolerence and expressions of anger
toward the spouse or offspring (Okasha and Maj, 2001).
There were no significant sex-specific differences in this
study among elderly depressed patients with respect to
medical comorbidity that the depressed patients usually
suffer from, such as DM, hypertension, cancer, cardiovascular disease, and arthritis. Absence of significant sexspecific differences implies that the physical comorbidity
is disease and age related rather than sex related, and this
is in agreement with the results of several studies
(Benazzi, 2009). There were no statistically significant
differences between elderly depressed men and women
with regard to somatic complaints on the somatization
scale of SCL (SCL-90): for example, headache, dizziness,
and gastrointestinal manifestations. These findings
agreed with the study that reported that depression in
medically ill elderly patients may present covertly, with
psychosomatic symptoms or with hypochondriasis, which
may make it difficult to distinguish from the coexisting
physical illness, and that these somatic complaints are
disease specific rather than sex specific (Gallo and
Rabins, 1999). Our study showed that there were no
statistically significant sex-specific differences among the
depressed patients. Although women are two or three
times more likely to be affected than men with anxiety
disorders and the mean age of presentation is about 25
years (Sadock and Sadock, 2004), these differences could
not be detected in our results reflecting different
etiological backgrounds. There were no significant
differences in the trait anxiety subscale, nor were there
any significant sex-specific differences with regard to
both subscales. In this study, depressed men reported
symptoms of sexual dysfunction in the form of decreased
libido more often than did depressed women; depressed
men also reported erectile dysfunction (ED). This may
be explained culturally as a lower disclosure rate among
women about their sexual life. Sexual needs across the
lifespan may not differ drastically, although older women
voice more concerns about their partner’s sexual difficulties (Nusbaum et al., 2004). Whether the age-dependent
decline in androgen levels leads to health problems in
men is being debated vigorously. Some investigators argue
that age-associated testosterone deficiency, or ‘andropause’, is responsible for many of the typical signs of male
aging, such as ED, skin alterations, and osteoporosis, and
for neuropsychiatric problems, such as fatigue, loss of
libido, depression, irritability, insomnia, and memory
impairment (Morales et al., 2000). If women do experience a decline in libido, this tends to start at or around
menopause rather than late in life. Subsequent to this,
sexual interest is influenced less by age than by health,
medication, and availability of a partner (Bretschneider
and McCoy, 1988). There were no statistically significant
sex-specific differences among depressed patients with
regard to hostility, interpersonal sensitivity, paranoid
ideation, and psychosis of SCL rating scale. This could
be attributed to the small sample size or it could be
considered as state specific rather than sex specific
(Bretschneider and McCoy, 1988). There were no
significant differences between depressed men and
women regarding the total score of MMSE and different
subscales except attention subscale, as depressed women
showed more lack of attention compared with depressed
men, as depressed elderly women had lower self-esteem
and more sense of worthlessness, which had its impact on
attention; the absence of other significant differences
could be explained by the fact that MMSE is a rapid
clinical screening test for detection of cognitive impairment rather than a sophisticated cognitive battery for
detection of notable cognitive impairment (Elderkin
Thompson et al., 2006). Depressed women showed more
disturbance in reasoning and abstract thinking and in
visual perception, imagination, and constructional abilities compared with depressed men. These findings
explained by the study reported that the processing
speed appears to be the most core cognitive deficit in
late-life depression as elderly depressed women showed
more psychomotor retardation and their attention was
more affected with consecutive effects of the previous
cognitive functions (Barch et al., 2001). Otherwise, there
were no significant sex-specific differences regarding the
global intellectual detrioration, verbal, performance, full
scales, and the grade of WAIS.
Conclusion
(1) Depression in old age is associated with widowhood.
Depression in elderly women is significantly associated with widowhood more than in elderly men.
(2) There was a significant difference in self-esteem,
which suggests that depressed women had a sense of
worthlessness more than did depressed men.
(3) Depressed men reported symptoms of sexual dysfunction in the form of decreased libido more than
depressed women; depressed men also reported ED.
(4) Depressed women showed more effects of lack of
attention compared with depressed men.
(5) Depressed women showed more disturbance in
reasoning and abstract thinking and in visual perception, imagination, and constructional abilities compared with depressed men.
Recommendations
A large-sized sample may be needed for detection of
other differences of old age depression between men and
women. Follow-up studies aiming at assessment of the
course and prognosis of old-age depression in men and
women are required. Comparative studies designed to
compare effects of cognitive and executive functions and
its relation to depression, especially vascular depression,
between elderly depressed men and women are required.
Elderkin Thompson V, Mintz J, Haroon E, Lavretsky H, Kumar A (2006). Executive
dysfunction and memory in older patients with major and minor depression.
Arch Clin Neuropsychol 21:669–676.
Essau CA, Lewinsohn PM, Seeley JR, Sasagawa S (2010). Gender differences in
the developmental course of depression. J Affect Disord 127:185–190.
Gallo JJ, Rabins PV (1999). Depression without sadness: alternative presentations of depression in late life. Am Fam Physician 60:820–826.
Hinton L, Zweifach M, Oishi S, Tang L, Unutzer J (2006). Gender disparities in the
treatment of late-life depression: qualitative and quantitative findings from the
IMPACT trial. Am J Geriatr Psychiatry 14:884–892.
Kalache A (2006). WHO’s perspective on active aging. In: World Health
Organization (WHO), editors. Active aging and promotion of the health of
older people. WHO, Geneva, Switzerland: World Health Organization
(WHO). pp. 4–16.
Kessler RC (2003). Epidemiology of women and depression. J Affect Disord
74:5–13.
Acknowledgements
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Original article 29
Memory impairment in female schizophrenic patients
and its relation with their female sex hormonal profile
Samia Abd EL-Rahman Ahmed, Ola Omar Shaheen,
Amany Ahmed Abdou and Mohamed Nasr El Din
Department of Psychiatry, Faculty of Medicine,
Correspondence to Amany Ahmed Abdou, Assistant
Professor, Department of Psychiatry, Faculty of
Medicine, Cairo University, Cairo, Egypt
Tel: + 20 105 214 720;
Hypothesis
Schizophrenic women show deficits in a variety of cognitive domains including
executive function, attention, memory, and language. The female sex hormone
estrogen acts as a neuroactive hormone that is assumed to have interesting
effects on the central nervous system and on the cognitive functions in specific.
Aim of the work
To determine the memory impairment in a sample of schizophrenic female patients,
as well as its relation to the level of their female sex hormone estradiol, to evaluate the
usefulness of hormonal therapy as an adjunct therapy to antipsychotic drugs in female
schizophrenic patients to improve their cognitive functions.
This is a comparative study that included 30 schizophrenic female patients who were
admitted for a long time as inpatients of Al Abasseia Psychiatric Hospital, and a control
group that matched in age and education. They were subjected to a psychiatric
interview, neurological examination, general examination, the scale for the assessment
of positive symptoms, and scale for the assessment of negative symptoms, serum
estradiol level during 3 consecutive weeks, and the Luria–Nebraska neuropsychological
battery, which is a multidimensional battery designed to assess a broad range of
neuropsychological functions. (We focused on the items that tested memory functions).
Results
There were statistically significant differences between both groups in the clinical
scales C10 (memory) of the Luria–Nebraska neuropsychological battery, as well the
factor scales concerned with memory ME1 (verbal memory) and ME2 (visual and
complex memory). The mean estradiol level was inversely correlated with the mean
of the memory scales; that is, an increased estradiol level was correlated with better
performance of the patient group in memory scales.
Conclusion
Female schizophrenic patients performed significantly worse in the memory scale (C10),
as well as the factor scales concerned with memory ME1 (verbal memory) and ME2
(visual and complex memory); the increased estradiol level was correlated with better
performance of the patient group in memory scales, which may be of value in these
patients when providing hormonal therapy as an adjunct therapy to antipsychotic drugs.
Keywords:
female sex hormones, memory impairment, schizophrenia
1110-1105
Introduction
Efforts to identify differential or core cognitive deficits in
schizophrenia have been made for several decades, with
limited success. Part of the difficulty in establishing
a cognitive profile in schizophrenia is the considerable
interpatient heterogeneity in the level of cognitive impairment. Thus, it may be useful to examine the presence of
relative cognitive weaknesses on an intraperson level
(Palmer et al., 2010).
Estrogen is a neuroactive hormone that exerts powerful
effects on the central nervous system, especially on
cognitive functions. The largest concentrations of estro1110-1105 & 2012 Egyptian Journal of Psychiatry
gen receptors-b are in the hypothalamus, the amygdala,
and the hippocampus (Shughrue and Merchenthaler,
2000). The neurotransmitter that estrogen upregulates
the most is acetylcholine (Luine, 1985), although it
affects the serotonergic, noradrenergic, and dopaminergic
systems as well (McEwen, 2002). Moreover, the hippocampus itself has been shown to be critical for explicit
or declarative memory. Sherwin and McGill (2003)
suggested that estrogen may exert the maximum effects
on memory, although this does not exclude the possibility
that estrogen might influence other cognitive functions
as well. Estrogens exert complex and time-dependent
effects on spatial and declarative memory in animals
DOI: 10.7123/01.EJP.0000411114.33017.6a
30
(Voytko, 1996; Fader et al., 1998; Gibbs et al., 1998; Green,
2006).
Also, estrogen has been postulated to have a positive
effect on short-term and long-term verbal memory in
postmenopausal women, as well as increasing the capacity
for new learning (Sherwin and McGill, 2003). Estrogen
replacement therapy (ERT) has an added benefit for
cognitive deficits in postmenopausal women with schizophrenia (Kulkarni et al., 1996).
Aim of the work
The aim of this study is to determine memory impairment in a sample of schizophrenic female patients, its
relation to their positive and negative symptoms, and the
level of the female sex hormone estradiol, to evaluate the
usefulness of hormonal therapy as an adjunct therapy to
antipsychotic drugs, to improve their cognitive functions.
History of neurological illness, epilepsy, head trauma,
mental retardation, acute medical illness, or substance
abuse.
Uncooperative patients.
History of electro convulsive therapy application in the
previous 6 weeks before examination.
Methods
Clinical assessment
(1) Psychiatric interview: the semistructured sheet of
the psychiatric department of Al Kasr El-Aini
Hospital, Faculty of Medicine, Cairo University was
used for the psychiatric interview of the patients.
(2) Neurological examination.
(3) General examination.
Psychiatric symptoms rating
The scale for the assessment of positive symptoms
(SAPS) and the scale for the assessment of negative
symptoms (SANS) were used (Andreasen, 1984a).
Participants
This Comparative case–control study was carried on a
sample of Egyptian women.
Patient group
This group included 30 patients fulfilling the Diagnostic
and Statistical Manual of Mental Disorders, fourth edition,
Text Revision diagnostic criteria for schizophrenia that
was confirmed by two other psychiatrists.
They were admitted to Al Abasseia Psychiatric Hospital
with at least 2 years of illness. They did not show acute
exacerbation. They were under treatment either by
conventional antipsychotics, atypical antipsychotics, or both.
Informed consent was obtained from the general director of
the hospital, from the patients, and their relatives.
Control group
The control group included 15 normal women. They were
subjected to a clinical assessment, which included
a detailed psychiatric interview and neurological and
general examinations, with neuropsychological evaluation
using the Luria–Nebraska neuropsychological battery
(LNNB). Also, the gynecological history was obtained
and hormonal assessment was performed. For every case,
two blood samples were obtained: one during menstruation and one on days 10–12 of the cycle. The women
selected in both groups fulfilled the following criteria:
Inclusion criteria: Women in the child-bearing period.
All patients should continue at least 6 years of education.
This was a necessity for completion of the psychological
evaluation.
Hormonal assessment
To assess the serum level of estradiol, three blood
samples were taken on 3 consecutive weeks (not two
samples) to nullify the effect of menstrual irregularities.
The hormonal assessment was performed at Kasr El-Aini
university hospital, the laboratory of the Obstetric and
Gynecology Department. The normal estradiol ranges
were as follows: the follicular phase (30–50 pg/ml),
periovulatory (150–450 pg/ml), the luteal phase (150–
230 pg/ml), and postmenopausal (0–25 pg/ml).
Neuropsychological assessment
LNNB (Golden et al., 1995) is a multidimensional battery
designed to assess a broad range of neuropsychological
functions.
Adaptation to the Arabic version was performed accurately with the agreement of professional judgments (one
senior psychiatrist and one senior psychologist). The
reliability of the LNNB has been examined from
a number of perspectives including interrater agreement,
split-half, internal consistency, and test–retest reliability,
and proven to be reliable. Also, criterion-related, concurrent, and construct validity of the LNNB has been
proven. We focused on items that tested memory:
Clinical scales: C10-memory; this scale basically tests shortterm and intermediate memory.
Factor scales: the factor scales resulted from a series of
studies in which each of the major scales of the test
Table 1 Age and educational level
Exclusion criteria: History of taking any synthetic steroids
(including oral contraceptive pills) before and during the
examination.
Pregnant women and those with ovarian dysfunction or
other gynecological problems.
Patient group
Mean age ± SD
P
Mean years of education ± SD
P
Control group
34.6 ± 6.8
34.6 ± 6.7
0.99
12.6 ± 2
12.67 ± 1.98
0.96
Memory impairment in female schizophrenic patients Ahmed et al. 31
Table 2 The scale for assessment of positive symptoms, the scale for assessment of negative symptoms
SAPS
No.
Mean ± SD
SANS
No.
Mean ± SD
Delusions
Positive formal thought disorder
Hallucinations
Bizarre behavior
Inappropriate affect
Total SAPS
30
30
30
30
30
30
33.6 ± 10.1
18.97 ± 8.2
13.9 ± 5.8
12.2 ± 3.2
3.1 ± 0.8
81.7 ± 20.4
Affective flattening or blunting
Anhedonia-asociality
Avolition-apathy
Alogia
Attention
Total SANS
30
30
30
30
30
30
19.97 ± 4.8
15.8 ± 3.8
11.0 ± 2.03
10.5 ± 4.6
7.87 ± 2.5
64.8 ± 13.7
SANS, scale for assessment of negative symptoms; SAPS, scale for assessment of positive symptoms.
Table 3 The three estradiol levels
Estradiol levels (E2)
Mean ± SD
Follicular phase
Patients No. = 28
Control No. = 15
Periovulatory phase
Patients No. = 30
Control No. = 15
Mean of estradiol levels in both phases
Patients No. = 30
Control No. = 15
57.4 ± 41.6
69.1 ± 22.2
151.9 ± 110.1
181.5 ± 131.8
112 ± 89.3
125.3 ± 69.1
Table 4 The results of Luria–Nebraska neuropsychological
battery in both patient and control groups
Group
Number
Mean ± SD
P
30
15
72.52 ± 10.2
43.80 ± 4.2
0.000*
C10 (memory)
Patients
Control
*Significant Po0.05.
Table 5 Factor scales
Factor scale
Group Number Mean ± SD
ME1(verbal memory)
ME2(visual and complex
memory)
P
Patients
Control
Patients
30
15
30
76 ± 7.95 0.000*
53.8 ± 5.2
62.6 ± 8.04 0.000*
Control
15
44.6 ± 4.7
Table 8 Correlation of E2 (mean estradiol levels) and scale for
assessment of positive symptoms and the scale for assessment
of negative symptoms
SAPS
Hallucinations
Delusions
Bizarre behavior
Positive formal thought disorder
Inappropriate affect
Total SAPS
SANS
Affective flattening or blunting
Alogia
Avolition-apathy
Anhedonia-asociality
Attention
Total SANS
No.
R
P
30
30
30
30
30
30
– 0.098
– 0.113
0.166
– 0.004
0.227
– 0.051
0.61
0.55
0.382
0.98
0.227
0.790
30
30
30
30
30
30
0.014
0.150
0.118
– 0.212
– 0.072
0.009
0.93
0.43
0.54
0.26
0.71
0.96
SANS, scale for assessment of negative symptoms; SAPS, scale for
assessment of positive symptoms.
battery was investigated in separate factor analyses
(Golden et al., 1995).
(1) ME1 (verbal memory). These items involve recalling
lists of words presented visually and orally. These
items require short-term verbal memory skills.
(2) ME2 (visual and complex memory). These items
involve drawing shapes, copying hand positions,
repeating stories, and repeating words associated
with pictures, all from memory. They require shortterm memory for visual stimuli, memory for combined verbal and visual information, and integration
of visual memory with motor skills.
Statistical techniques used
Table 6 Correlation of the mean E2 and clinical scales: E2 and
C10 (memory)
Total number
R
P
30
15
– 0.380
– 0.106
0.038*
0.707
Patients
Control
Percentages, means, and SD were calculated. A t-test and
Pearson correlation were also performed using the SPSS
(version 11, IBM, Armonk, New York, USA) analysis
computer program (Table 1).
Results
Demographic and clinical data
Table 7 Correlation of the mean E2 and factor scales
LNNB scales
ME1(verbal memory)
ME2 (visual and complex
memory)
Group
Total
No.
Patients
Control
Patients
30
15
30
– 0.766* 0.027*
– 0.547* 0.035*
– 0.585* 0.012*
Control
15
– 0.877* 0.000*
LNNB, Luria–Nebraska neuropsychological battery.
R
P
There were no statistically significant differences between both groups in terms of the mean age and the
mean years of education.
Occupation, marital status, family history, and history of
menstrual disturbance: there was a higher percentage of
working women in the control group in comparison with
80% nonworking schizophrenic patients. Also, most of them
were married in contrast to more single and divorced
schizophrenic patients. 36.7% of schizophrenic patients had
menstrual irregularities compared with none in the control
group. 53.3% of schizophrenic patients had a family history
of psychosis in contrast to 6.7% in the control group.
performance of memory function (short-term and intermediate memory) in patients with schizophrenia but not
in the control group.
Table 2 shows that delusions and positive formal thought
disorders were the most common positive symptoms in
our patients. Also, affective flattening or blunting and
anhedonia-asociality were the most common negative
symptoms in the patient group.
Table 7 shows that the mean estradiol level is inversely
correlated with the mean of scales ME1 (verbal memory)
and ME2 (visual and complex memory), and this
correlation was statistically significant in both the patient
and the control group.
Hormonal assessment
Results of serum estradiol measurements: for the patient
and control groups, the first samples presented a serum
level of estradiol in the follicular phase and the second
samples presented a serum level in the periovulatory
phase. We excluded two patients as the first samples were
more than 300 pg/ml. Thus, these samples did not
represent the follicular phase in those patients. The
serum estradiol levels measured in the third samples for
the patient group were only used when assessing the
correlation of estradiol level and different scales of LNNB.
Table 3 shows that the mean serum estradiol level in all
phases was higher in the control group than that in the
patient group.
The critical level
The critical level represents the highest LNNB score,
which can be considered normal for the battery and is
adjusted for both age and education. Thus, scores above the
critical level are considered impaired and scores below this
level are considered normal. The critical level represents
the cutoff point in other tests; it was 57.76 ± 3.28 in the
patient group in contrast to 57.66 ± 3.11 in the control
group, and there was no significant difference between the
patient and the control group as P-value was greater than
0.05. This is very important for comparison of both.
Clinical scales
Table 4 also shows that there were statistically significant
differences between the patient and control groups in the
performance of C10 (memory). The patient group
performed above the critical levels in this scale and the
control group performed below the critical level ,that is,
memory is impaired in the patient group and intact in the
control group.
Table 5 shows that there were statistically significant
differences between the patient and control groups in
terms of their performance on factor scales ME1 (verbal
memory) and ME2 (visual and complex memory). The
patient group performed above the critical levels on these
factor scales and the control group performed below the
critical level. This means that these functions are impaired
in the patient group and intact in the control group.
Results of correlations
Table 6 shows that the mean estradiol level was inversely
correlated with the scores of the C10 (memory) in the
patient group and this correlation was significant
statistically as P-value was less than 0.05. This means
that a high estradiol level is correlated with good
Table 8 shows that the mean estradiol levels of the
patient group showed no significant correlation between
the total SAPS and subscales of SAPS as the P-value was
greater than 0.05 in all the correlations.
Discussion
This study is a case–control comparative study, with no
statistically significant difference regarding age and years
spent in education that was necessary in order to be able
to complete the LNNB. Low rates of marriage in the
patient group could be explained by the effect of the
psychotic disorder on the patients’ coping mechanisms
and the effect of the psychotic disorder on patients’
abilities to maintain normal life to maintain the relationship. Also, the early onset of schizophrenia may explain
the low rates of marriage in some patients. Our results
agree with those of Halari et al. (2004), who reported low
number of married individuals among schizophrenic
patients. The scale for the assessment of positive
symptoms (SAPS) and scale for the assessment of
negative symptoms (SANS). Andreasen (1984b) mean
of total SAPS, delusions subscale, positive formal thought
disorder, hallucinations subscale and bizarre behavior
subscale were within the range of mild-moderate in
severity. The means of total SANS, affective flattening or
the blunting subscale of SANS, the Anhedonia-asociality
subscale, the avolition-apathy subscale of SANS, the
alogia subscale, and the attention subscale were within
the range of mild-moderate severity. The scores of SAPS
were inversely correlated with the scores of SANS. Thus,
the means of SAPS and SANS for all the patients were in
the mild to moderate range. Another explanation was that
we excluded patients with marked to severe positive or
negative symptoms, who may not be cooperative during
the cognitive assessment. As regards the results of the
hormonal assessment, the mean serum estradiol levels in
the follicular phase, periovulatory, and both phases for the
patient group were lower than those of the control group.
We considered patients to have hypoestrogenism when
they had a serum estradiol level below 30 pg/ml in the
follicular phase and/or below 150 pg/ml in the luteal or
periovulatory phase according to the laboratory of
Obstetric and Gynecology Department at Kasr El-Aini
university hospital. Thus, all the control cases were
within normal levels. Five patients had hypoestrogenism
in the follicular phase, nine patients had hypoestrogenism
in the luteal or periovulatory phase, and four patients
showed hypoestrogenism in both follicular and luteal
phases. Thus, a total of 18 patients (60%) showed
hypoestrogenism. This result agrees with that reported
by Bergemann et al. (2005), who found hypoestrogenism
Memory impairment in female schizophrenic patients Ahmed et al. 33
in 57.3% of the patients. Also, our result agrees with Ko
et al. 2006, who found hypoestrogenism in 62.8% of
patients with schizophrenia. There are many explanations
for the hypoestrogenism in our study. Most of our
patients (96.7%) were on treatment with conventional
antipsychotics, which in particular are known to induce
hyperprolactinemia, which reduces estrogen levels.
The C10 (memory) scale basically tests short-term and
intermediate memory. The study found that the patient
group had mean scores of the C10 above the critical level.
Also, the patient group performed significantly above the
control group on scale C10. This means that schizophrenic patients had significant memory impairment.
Also, there were statistically significant differences
between the patient and control groups on factor scales:
ME1 (verbal memory) and ME2 (visual and complex
memory). Thus, impairment in schizophrenic patients
involved short-term and intermediate memory, verbal
memory, visual, and complex memory. This memory
impairment may contribute to the development of the
psychopathology of schizophrenia. These results agree
with those reported in the literature. Valsharkey et al.
(2000) reported that impaired memory is a prominent
feature of schizophrenia. In general, patients tend to be
impaired more on difficult memory tasks that require
active processing of materials, whereas procedural learning that involves motor skills may be less impaired. Hoff
et al. (2001), reported that with age and education
controlled, the first-episode and chronic patients with
schizophrenia performed significantly worse than the
normal participants on neuropsychological summery
measures of verbal memory and spatial memory Danion
et al. (1999), and Kuperberg and Heckers (2000) reported
that memory deficits in schizophrenia are associated with
an inability to link the separate aspects of events into a
cohesive, memorable, and distinctive whole. Also, working memory deficits are well known in schizophrenia
(Quintana et al., 2003; Meda et al., 2009; Palmer et al.,
2010) Although most of the previous studies did not use
the LNNB, it was highly correlated with tests of memory.
For example, Buchanan et al. (2004) found a correlation
between the Wechsler Memory Scale (Wechsler, 1987)
and the LNNB C10 scale. They also found a 72%
agreement between the scales on identification of
memory impairment, and there are many correlation
studies on the LNNB and other psychological tests,
which are beyond the scope of this discussion. This is
important so that we can compare the results from the
LNNB with the results of other tests.
In terms of the results of correlations, the study proved
that the mean estradiol levels were inversely correlated
with the mean performance of the C10 (memory)
measuring short-term and intermediate memory, ME1
(verbal memory), and ME2 (visual and complex memory). All these correlations were statistically significant.
This means that a high estradiol level is correlated with
good performance of memory function (short-term and
intermediate memory, verbal memory, visual and complex
memory) in patients with schizophrenia but not in the
control group.
In our study, the estradiol level was correlated with higher
performance on memory. These results agree with those
reported by Ko et al. (2006) and Hoff et al. (2001), who
reported that serum estradiol levels showed direct
significant correlations with the verbal memory, verbal
fluency, and executive functions, and also with Sherwin
and McGill (2003), who found that estrogen has a
positive effect on short-term and long-term verbal
memory in postmenopausal women, as well as increasing
the capacity for new learning. However, the study
disagrees with Halari et al. (2004), who failed to found
any correlation of estrogen with any cognitive domains.
Other studies failed to find any effect of estrogen on
cognitive functions in postmenopausal women for
example: Duff and Hampson (2000) and Janowsky et al.
(2000). Also, no differences in scores on tests of verbal
memory, occurred in women 81 years old treated with
either estrogen or progestin compared with those treated
with placebo (Binder et al., 2001). Moreover, Barch et al.
(2003) reported that estrogen plus progestin did not
improve cognitive functions in women aged 65 years when
compared with placebo. The study of Seeman and
Fitzgerald (2000) summarized the possible roles of ERT
itself as a hormonal therapy in female patients with
schizophrenia, in that estrogen may be a useful addition to
antipsychotic medication in terms of downregulating
dopaminergic transmission and by its action on the
serotonin system. Estrogen helps to ameliorate cyclical
symptomatic fluctuations in women with resistant symptoms. It also preserves bone density and prevents
cardiovascular disease, especially in menopausal women;
also, estrogen may play a role in ameliorating or preventing
symptoms of tardive dyskinesia. In addition, it can be used
to counter the unwanted hyperprolactinemia effects that
may have accompanied a lifetime of treatment with older
antipsychotic medication (Kuperberg and Heckers, 2000).
Also, Zec and Trivedi (2002) reported that ERT acts to
maintain some aspects of cognition in postmenopausal
women, especially verbal memory and learning, as their
performance was better in 47% of memory measures in
women who received ERT. Moreover, across these studies,
there was a significantly higher percentage of significant
positive findings for the tests of verbal compared with
visual memory performance with ERT.
The results of this study should be interpreted in the
light of the following limitations: first, we did not include
a normal control group with a low estrogen level to
compare the results and the specificity of estrogen to
memory impairment. Second, our sample was obtained
from Alabbasia hospital with a high institutionalization
rate with its impact on cognitive functions.
Conclusion
(1) Schizophrenia is associated with a poor work record
and low marriage rates.
(2) Female schizophrenic patients had a history of
menstrual irregularities more than healthy normal
34
controls. Sixty percent of schizophrenic patients had
hypoestrogenism at some point in their menstrual
cycle.
(3) Schizophrenic patients performed significantly worse
than the normal healthy controls on the memory
scales of the LNNB: clinical scale (C10) and the
factor scales: ME1 (verbal memory) and ME2 (visual
and complex memory).
(4) Increased estrogen level was correlated with better
performance of the patient group, as well as in healthy
menstruating women in memory (intermediate-memory
and short-term memory), verbal memory, and visual
complex memory domains.
(5) The estrogen level is not correlated with positive or
negative symptoms of schizophrenia.
Recommendations
(1) Further studies should be conducted to examine the
effect of estrogen on other cognitive domains, that is,
other memory aspects, for example, working memory,
language, intellectual abilities, or on the patient’s
functioning, quality of life, as we see part of the
difficulty in establishing a cognitive profile in
schizophrenia is the considerable interpatient heterogeneity in the level of cognitive impairment. Thus, it
may be useful to examine the presence of relative
cognitive weaknesses at an intraperson level.
(2) A larger sample can be used and unhospitalized
patients can also be studied.
(3) Follow-up studies can be conducted for schizophrenic
patients after hormonal replacement therapy when
indicated and they can be compared with normal
women receiving the same hormonal therapy as
regards their cognitive abilities in order to examine
the benefits of hormonal replacement therapy.
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hormone replacement therapy on cognitive performance in elderly women.
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(2004). Morphometric assessment of the heteromodal association cortex in
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Original article 35
Impact of the first national campaign against the
stigma of mental illness
Nahed Khairya, Emad Hamdia, Albert Sidrakb, Noha Sabrya,
Mohamed Nasreldina, Aref Khoweileda and Nasser Lozab
a
Cairo University and
b
Mental Health Secretariat, Ministry of Health,
Cairo, Egypt
Correspondence to Mohamed Nasreldin, MD,
Assistant Professor of Psychiatry, Department of
Psychiatry, Faculty of Medicine, Cairo University, Cairo,
Egypt
Tel: + 01223267788; fax: + 233386951;
Received 6 April 2011
Background
Egypt experienced its first nationally televised antistigma campaign in 2007. This
independent study aims at a scientific evaluation of the potential benefits of this
campaign.
Methods
Two educational clips lasting 1 or 2 min each were aired daily on prime time television
between 1 and 31 October 2007. Five messages were relayed as the clip rolled on.
A specially designed questionnaire covering six areas was used; these included
demographics, identifying those who have seen the clips, memory and opinion about
each message, stigma-related attitudes, and behavior toward the mentally ill persons.
Twenty mental health workers with experience in field work ranging in training from 1 to
13 years received two training sessions. The questionnaire was piloted on 82
participants and subsequently modified. A total of 3000 participants who consented to
being interviewed were selected to participate. The data of 2274 participants from the
Greater Cairo region are reported in this study (75.8%).
Results
The study sample is more representative of the younger, as only 21% of the sample
were above 46 years, educated, as only 18% were illiterate, married, as 55% of the
sample were married, and employed sections of the population. A total of 55%
reported that daily life stressors were the cause of mental illness. Only 17% of
the study sample actually acknowledged seeing the antistigma adverts (campaign
exposed, CE) and 83% were campaign unexposed. There were no statistically
significant demographic differences between both groups. Among those who saw
the campaign adverts, a significant proportion reported a number of positive effects on
attitude and behavior. However, when CE and campaign unexposed participants were
compared, no statistically significant differences emerged. A total of 50% of the
participants remembered that mental illness is curable. The question that psychiatric
patients are dangerous to self or others showed a statistically significant difference
between participants who were CE and those who were not exposed.
Conclusion
The public were willing to express their opinions as they showed significant
cooperativeness and validity of their answers, especially those exposed to the
campaign. The television is the medium of choice that the public prefer is the
evidence stated in the paper. The antistigma media campaign leads to changes
in the attitude of participants who are exposed to mental illness. Positive messages
influenced attitude change more.
Keywords:
antistigma, mental illness, stigma, television
1110-1105
The stigma and discrimination experienced by persons
with mental illness is a universal phenomenon. It is also
linked to patients’ families, psychiatric institutions, and
psychotropic medications (Sartorius et al., 1996).
mental health services, and in those with limited services
(Brundtland, 2001). Stigma is pernicious and unfortunately, there are indications that despite advances in
psychiatry and medicine, stigma continues to grow and
has more often terrible consequences for patients and
families (Brundtland, 2001).
Unlike other medical conditions, mental illness is recognized as an important barrier in countries rich and
poor, big and small, in countries with well developed
Mental health professionals are aware of the harmful
effect of stigma against mental illness. It interferes at
every stage in the diagnosis, treatment, and rehabilitation
Introduction
DOI: 10.7123/01.EJP.0000411119.59113.6e
36
of all types of mental disorders, and even forces people to
avoid seeking psychiatric help. Fighting this stigma can
improve the outcome of the disease, and allow the
patients to make use of the new modalities of treatment
that bring new hope to them (Wig, 1997).
Stigma has long been viewed as a major barrier to mental
health reform and community integration for people with
mental disorders. Efforts to remove or reduce stigma are
still in their infancy. Therefore, implementing antistigma
programs to generate new knowledge and reduce
discrimination toward people with mental disorders is
necessary [World Psychiatric Association (WPA), 1998].
Aim of the work
Stemming from the hypothesis that utilizing media can
modify population’s attitude toward mental illness, this
work aims at evaluating the utilization of media (through
airing two educational clips targeted at raising awareness
about the nature of mental illness and its curability) on
the sample population.
Participants
The total number of participants interviewed was 3000; in
this study, data from 2773 participants are reported. For the
remaining 227 participants, various mistakes in data collection, data recording, and data entry necessitated exclusion
(noncompletion rate 7.5%). The data collected are representative of the nationally recognized representative numbers of age groups, literacy groups, and sex (according to the
2007 census). Interviewing of the participants was completed over 5 weeks covering greater Cairo and other
dispersed areas. Interviews were individually conducted (one
on one). In the case of illiteracy, the questionnaire would be
read without explanation in order not to influence choice.
The antistigma campaign
Two educational clips lasting about 2 min each aired on
prime time television (TV) within the breaks of two
nationally acclaimed household programs during the period
of 1–31 October daily during Ramadan in 2008. Clip 1
shows a conversation between the actors, one posing as a
recovered psychiatric patient and the other posing as a
salesman who has a dramatic change in attitude when he
finds out that he is speaking to a mentally ill person. Clip 2
shows an encounter between two people, one applying for a
job and the other a human resource manager. The former is
rejected on the basis of his psychiatric history. Five
messages were narrated as the clip rolled on. These
messages were as follows: (i) daily stressors are among the
causes of mental illness; (ii) an invitation to critically
appraise the following sentence: ‘This is a psychiatric
patient, stay away’; (iii) mental illness is recognizable,
diagnosable, and treatable; (iv) mental illness is like any
other illness, potentially curable; and (v) an invitation to
critically appraise the following sentence: ‘Once mentally
ill, always mentally ill’. Assessment instrument: a specially
Table 1 Characteristics of the survey participantsa
Variable
Sex
Male
Female
Age (mean = 34 years)
14 years or less
Between 15 and 25
Between 26 and 36
Between 36 and 45
Between 46 and 59
Above 60
Marital status
Married
Single
Divorced
Widowed
Educational level
Illiterate
Can read and write
Primary
Preparatory
Secondary
Technical degree
University degree
Employed/unemployed
Employmentb
Unemployed
Housewivesc
Students
Retired
Type of Work
Skilled
Unskilled
Admin/clerical
Professional
Self-employed
Experience with mental illness
No EMI
Any EMI
Self
Relative
Self and relative
Exposure to Campaign
Campaign Exposed
Campaign Unexposed
N = 2701
Population (%)
1400
1373
51%
49%
44
963
693
417
417
167
N = 2768
1510
1062
53
143
N = 2773
504
212
41
290
750
207
679
N = 2737
1909
137
405
284
2
1.6%
34.7%
25%
15%
15%
6%
Population (%)
55%
38%
2%
5%
Population (%)
18%
7.6%
1.5%
10.5%
27%
7.5%
28%
Population (%)
69%
5%
15%
10%
0.1%
518
277
531
179
346
N = 2773
2438
369
101
251
17
N = 2773
459
2284
19%
10%
19%
6.5%
12.5%
Population (%)
86.7%
12%
3.6%
9%
0.7%
Population (%)
16.6%
82.4%
EMI; experience with mental illness.
a
Total number on which percents are based may vary because of
missing data for some participants.
b
Including both full-timers and part-timers.
c
Status of housewives in the Egyptian Society discussed within the
paper.
Table 2 Beliefs about the causes of mental illness and the
factor that needs to be addressed/manipulated to alleviate
stigma
Variable
Beliefs about the causes of mental illness
Stressors
Lack of religion/faith
Heredity
Upbringing
Addiction
Message required to get through
Psychiatric illness is like any other illness
Psychiatric patients get well
Reassessment of stereotypes is required
Psychiatric illness is not synonymous to
dangerousness
Some geniuses have had psychiatric illness
N = 2773
%
1557
448
325
300
127
56.1%
16.1%
11.7%
10.8%
5.1%
1098
536
493
418
40%
19%
18%
15%
220
8%
Impact of the first national campaign Khairy et al. 37
Table 3 Comparison between those who had watched the clip (campaign exposed) and those who had not watched the clip
(campaign unexposed)
CU (N = 2284)
CE (N = 459)
Variable
N
%
N
%
P
Sex
Male
1181
51.7
199
43.3
Po0.001
w2 = 13.8
1103
34 ± 13.6
48.3
260
33 ± 13.4
56.6
639
28
70
15.2
276
778
595
12.1
34
26.1
54
175
160
11.8
38.1
34.1
655
29.1
162
35.8
Employed
Marital status
Single
1598
70.9
291
64.2
865
38
185
40.3
Married
Divorced/widowed
Message remembered
Daily stressors may be responsible
‘This is a psychiatric patient: stay away’
Mental illness is diagnosable and treatable
Mental illness is like any other illness
‘If a psychiatric patient once, always a psychiatric patient’
Message agreed with
Daily stressors may be responsible
1244
170
54.5
7.5
N = 2248
1998
%
87.5
248
26
N = 459
203
216
229
219
178
N = 459
423
54
5.7
%
44
47
50
48
39
%
92
‘This is a psychiatric patient: stay away’
1776
78
402
88
Mental illness is diagnosable and treatable
1893
83
414
90
Mental illness is like any other illness
1242
54
315
69
391
17
45
10
517
27
83
18
Psychiatric illness is related to will power
1241
54
284
62
Psychiatric patients are dangerous to self or others
1815
79.5
319
70
384
17
64
15
N = 2284
198
%
9
24
5
Marriage (self or relative)
751
33
219
48
To isolate
701
31
95
21
Hilarity
378
16
45
10
Employ
1223
53.5
296
64.5
678
30
117
25.5
1672
60
351
82
546
58
20
2
96
7
15
3
1752
76.7
381
83
487
40
21.3
1.8
68
8
15
2
256
118
48
20
9
7
56
26
10.5
4.4
2
1.5
1028
778
294
96
60
19
45
34
13
4.2
2.6
0.8
Female
Mean age
Educational status
Illiterate/read and write
Primary/preparatory school
Secondary school/vocational education
University degree
Employment status
Unemployed
‘If a psychiatric patient once, always a psychiatric patient’
Concepts leading to discrimination of mental patients
Psychiatric patients are exaggerating
All criminals are psychiatrically ill
Attitude towards mental patients
Friendship
Would stay at home if psychiatric patient
Neighbor’s illness
Visit
Phone
Relocate
Relative’s illness
Seek psychiatric help
Faith healer
Traditional healer
Tool recommended to influence public opinion
TV
Cable
Places of worship
Newspapers
Posters
NGOs
CE, campaign exposed; CU, campaign unexposed; NGO, nongovernmental organization; TV, television.
t = 0.78
Po0.4
Po0.0001
w2 = 48.8
Po0.004
w2 = 0.28
Po0.48
w2 = 7.4
Po0.008
w2 = 17.2
Po0.0001
w2 = 46.6
Po0.0001
w2 = 32.4
Po0.0001
w2 = 37.7
Po0.000
w2 = 29.6
Po0.13
w2 = 7.1
Po0.298
w2 = 9.5
Po0.0001
w2 = 24.9
Po0.959
w2 = 1.5
Po0.026
w2 = 17.4
Po0.0001
w2 = 45.8
Po0.002
w2 = 20.4
Po0.041
w2 = 18.9
Po0.011
w2 = 19.8
Po0.317
w2 = 9.3
Po0.36
w2 = 8.7
Po0.07
w2 = 11.5
38
designed questionnaire was prepared by E.H. and N.K. in
colloquial Arabic. The questionnaire consists of six sections
that include the following: demographics (age, marital
status, educational level, employment if any, and type of
job), identifying people who have seen the clips or posters,
inquiring whether each message is remembered and
gathering opinion about it, attitude toward the mentally
ill persons, and behavior toward the mentally ill persons. It
was handed out by social workers and a psychologist who
attended two training sessions.
Data entry and statistical analysis
A predesigned SPSS (Version 15, IBM, Chicago, IL, USA)
datasheet was distributed to all participants, and training
on data entry and coding was conducted in collective
setting, where all administrators and data enterers were
present. Four of the administrators were supervised by
one of the researchers. Data analysis was carried out using
the SPSS version 16. Simple descriptive statistics were
used as frequencies and percentages for descriptive
purposes. Inferential statistics for categorical data in the
form of the w2-test were used to compare the results of
the different study groups. The P-value was considered
significant at less than 0.05.
Results
Regarding the characteristics of the survey participants, the
study results showed that 51% of the study sample were
men and the mean age was 34 years, 55% of the sample
were married, only 28% were university degree educated,
86.7% had no experience with mental illness, and 82% were
campaign unexposed (Table 1). Regarding the beliefs on
the causes of mental illness and the factor that needs to be
addressed/manipulated to alleviate stigma stressors as a
cause of mental illness, 56.1 and 40% of the study sample
Table 4 Comparison between participants who are psychiatrically naive and those who are psychiatrically exposed (whether
for self, for a relative, or both)
Variable
Message agreed with
Psychiatric patients get well
Psychiatric illness is like any other illness
Reassessment of stereotypes is required
Psychiatric illness is not synonymous to
dangerousness
Some geniuses have had psychiatric illness
PN
PE
N (%)
N (%)
456
903
375
193
(20)
73 (16)
(39.6) 186 (40.6)
(16.4) 110 (24)
(8.5)
25 (5.4)
350 (15.3)
64 (14)
PE, psychiatrically exposed; PN, psychiatrically naive.
reported that psychiatric illnesses are like any illness
(Table 2). On comparing participants who had watched the
clip (campaign exposed) with those who had not watched
the clip (campaign unexposed), statistically significant
differences were observed between them regarding the sex
of the participants, educational level, opinion on the
messages, and attitudes toward mental illness (Table 3).
Comparison between participants who are psychiatrically
naive (PN) and those who are psychiatrically exposed (PE;
whether for self, for a relative, or both) showed that 20% of
those who were PN and only 16% of those who were PE
reported that psychiatric patients get well. In addition,
40.6% of the population who were PE reported that
psychiatric illness is like any other illness (Table 4). Comparison between participants who are campaign exposed
and those who are campaign unexposed regarding uncooperativeness and the validity of their answers showed a
statistically significant difference (Table 5).
Discussion
Stigma has long been viewed as a major barrier to mental
health reform and community integration for people with
mental disorders. Knowledge on how to remove or reduce
stigma is still in its infancy (Sartorius, 2000). Regarding
the beliefs that influence stereotype formation, our
results showed that stressors were a cause of mental
illness, followed by lack of religion/faith, followed by
heredity and upbringing, respectively. This highlights the
importance of a future antistigma program to generate
new knowledge about causal mechanisms underlying
mental illness as it is consistent with the result that
40% of the sample reported that the message required to
get across was that psychiatric illness is like any other
illness (Lauber et al., 2004). In addition, these reflect the
need for an effective antistigma program to reduce
discrimination of people with mental disorders to build
confidence in mentally ill persons, family members,
program funders, and policy makers.
TV and cable are the tools recommended to deliver future
messages and influence public opinion as they target a very
large number of people freely and are considered as
important tools to inform and educate the public about
mental illness and promote the acceptance of mental
illness as the majority of our community received limited
education or were illiterate and only 35% of the sample
were university or secondary degree educated (Arboleda
Florez, 2003; Al Gohary, 2005). The broadcast messages
reached only 20% of the study sample (campaign exposed),
with a higher number of women, which did not match the
Table 5 Comparison between participants who are campaign exposed and those who are campaign unexposed regarding
uncooperativeness and validity of their answers
CE
CU
Total
t-test
Cooperativeness of interviewed participants
8.77 ± 1.24
8.46 ± 1.27
8.51 ± 1.28
Validity of interviewed participants
8.51 ± 1.34
8.21 ± 1.33
8.25 ± 1.35
T = 4.72
Po0.0001
T = 4.38
Po0.0001
CE, campaign exposed; CU, campaign unexposed.
Impact of the first national campaign Khairy et al. 39
Austrian (9) initiative to use mass media as an antistigma
tool as the broadcast message reached 46% of the total
television viewing audience. This could be attributed to the
time of broadcasting the clip, which was during Ramadan
after breakfast at the time of prayer and on national TV,
which has a limited audience compared with cable. A higher
number of women watched the clip as they are at home for
a longer period of time than men (Al Gohary, 2005). There
are a statistically difference between the two groups those
who watched the clip and those who has not along the
different messages agreed upon it. In addition, the clips
were supposed to convey their messages focusing on one of
the three outcomes: an improvement in knowledge,
attitude, or behavior (Okasha and Stefanis, 2005). These
messages were that daily stressors may be responsible for
reflecting knowledge about mental illness; ‘This is a
psychiatric patient: stay away,’ reflecting a behavior toward
mental illness and measuring social distance (Okasha and
Stefanis, 2005); mental illness is diagnosable and treatable,
reflecting knowledge about mental illness (Okasha and
Stefanis, 2005); mental illness is like any other illness,
reflecting knowledge and a tolerant attitude toward mental
illness; and ‘If a psychiatric patient once, always a
psychiatric patient’, reflecting knowledge about mental
illness (Okasha and Stefanis, 2005). All these messages
highlighted the fact that the most relevant objectives for
mentally ill persons and family members relate to the way
people behave toward people with a mental illness and the
societal structures that create and perpetuate social
disadvantages (Amer et al., 2007; Hamdi et al., 2007). This
means that the messages were clear, relevant, understandable, and considered to be measurable outcome results
of the antistigma clips, and it coincided with the WPA’s
mission to improve the lives of mental patients and to
reduce the discriminatory behavior that has the most direct
and damaging effect (Brundtland, 2001). Early successes of
any program related to short-term outcomes create agreement, morale community support and can be used to
marshal the additional resources needed to bring about
long-term changes (Posavac and Carey, 1992). However, one
of the pitfalls of this program is the absence of pretesting to
compare the results (preprogramming and postprogramming), to measure existing levels of knowledge, attitudes, or
socially distancing behavior in the population, to identify
problems in logistics and familiarity or difficulty of the
words to increase the usability of the results. However, good
antistigma outcomes also need to be strategic. In this
context, strategic means directing efforts to specific
subpopulations, and our program was directed toward the
general population. Regarding the potential impact of
psychiatric exposure (PE) on the response to the campaign,
the comparison between participants who are PE (whether
for self, for a relative, or both) and those who are PN
showed a statistical significance.
Conclusion
The public are willing to express their opinions as they
showed significant cooperativeness and validity of their
answers, especially those exposed to the campaign. The TV
is the medium of choice that the public prefers is the
evidence stated in the paper. The antistigma media
campaign led to changes in the attitude of participants
who were exposed to mental illness and its results could be
generalized had the outcomes been clearly identified, preexposure and postexposure assessment; the postexposure
assessment should be carried out shortly after the exposure,
the given questions should be standardized and simple, and
finally proper time for broadcasting should be chosen.
Positive messages influenced attitude change more.
Acknowledgements
A Christian Orthodox NGO by the name of ‘‘The Best Life’’ provided the
volunteers, who were trained to conduct the questionnaire and enter
data. This organization provides services for combating drug addiction
and the stigma of AIDS. The Finnish mental health program for Egypt
funded the research.
References
Al Gohary M (2005). Record mental illness representation in Egyptian folklore. In:
Othman S, Sa’dalla N, editors. Health and sickness: a socioanthropological
perspective. Alexandria: Dar L Aa’refa al Gami’’eya.
Amer D, Abdou A, Nasreldin M (2007). Cultural beliefs and help seeking behavior
in Egyptian psychiatric patients and their families. J Ment Illn 40:150–165.
Arboleda Florez J (2003). Considerations on the stigma of mental illness.
Can J Psychiatry 48:645–650.
Brundtland GH (2001). From the World Health Organization. Mental health: new
understanding, new hope. JAMA 286:2391.
Hamdi E, Rakhawy M, Sabry N, Ramy H, Hamed H, Rakhawy M, et al (2007).
The attitude and use of faith healing by people with mental disorders:
a community survey. Arab Journal of Psychiatry 21:24–49.
Lauber C, Nordt C, Falcato L, Rössler W (2004). Factors influencing social
distance toward people with mental illness. Community Ment Health J 40:
265–274.
Okasha A, Stefanis CN (2005). Perspectives on the stigma of mental illness.
Geneva: World Psychiatric Association (WPA).
Posavac EI, Carey RG (1992). Program evaluation: methods and case studies.
4th ed. Englewood Cliffs, New Jersey: Prentice Hall.
Sartorius N (2000). Breaking the vicious cycle. Ment Health Learn Dsiabil Care
4:80.
Sartorius N, Gulbinat W, Harrison G, Laska E, Siegel C (1996). Long-term followup of schizophrenia in 16 countries. A description of the International
Study of Schizophrenia conducted by the World Health Organization. Soc
Psychiatry Psychiatr Epidemiol 31:249–258.
Wig NN (1997). Stigma against mental illness. Indian J Psychiatry 39:187–189.
World Psychiatric Association (WPA) (1998). Global program against stigma
and discrimination because of schizophrenia. Bourg - Switzerland: World
Psychiatric Association (WPA).
40
Original article
Cognitive functions in euthymic adolescents with juvenile
bipolar disorder
Lamis El Ray, Aref Khoweiled, Hoda Abdou, Shreen Abd El-Mawella
and Mai Abdel Samie
Correspondence to Lamis Ali El Ray, Department of
Psychiatry, Faculty of Medicine, Cairo University, Cairo,
Egypt
Tel/fax: + 02 23651929;
e-mail: lamis [email protected]
Received 22 December 2010
Accepted 24 March 2011
Introduction
Bipolar disorder in adolescents is often referred to as juvenile bipolar disorder. A peak
in the prevalence of bipolar disorder has been documented between the ages of
15 and 19 years. Wide-ranging neuropsychological deficits have been found in many
studies of juvenile bipolar disorder. Persistent neuropsychological deficits present in the
euthymic state suggest that such deficits could be vulnerability trait markers of the illness.
Aim
To identify and assess cognitive functioning in euthymic adolescents diagnosed with
bipolar disorder.
A case–control cross sectional study, in which 30 euthymic bipolar adolescents were
recruited from the psychiatric adolescent clinic of Kasr al Ainy and compared with
30 healthy controls.
Psychometric procedure
The Hamilton Rating Scale of Depression, the Young Mania Rating Scale, the letter
cancellation test, the digit span and digit symbol/coding tests, the Bender gestalt test
and the Wisconsin card sorting test were used.
Results
Cases had significantly higher mean scores than controls in the letter cancellation test
and its omission errors as well as in the perseverative errors of the Wisconsin card
sorting test, and lower mean scores in the digit span, digit symbol coding and the
Bender gestalt tests. There was a significant positive correlation between the number
of omission errors on the letter cancellation test and both of the number of manic
episodes and the age of onset of the illness.
Conclusion
There are neuropsychological deficits in the areas of sustained attention, set shifting,
processing speed and visual and auditory short-term memory in euthymic bipolar
adolescent patients, type I. There is a significant correlation between the number of
manic episodes as well as age of illness onset and sustained attention.
Keywords:
euthymia, juvenile bipolar disorder, neuropsychological deficits
1110-1105
Introduction
Bipolar disorder in adolescents is often referred to as
juvenile bipolar disorder (Cahill et al., 2009). It is a
disabling condition characterized by extreme affective and
behavioural dysregulation, aggression, severe irritability
and a chronic course (Biederman, 2003). In clinical trials,
euthymia in bipolar disorder is conventionally defined as
scores below a certain threshold, but not zero, on the
Young Mania Rating Scale and the Hamilton Rating Scale
for Depression (HRSD) (Pizzagalli et al., 2008). During
euthymia, bipolar patients exhibit minimal symptoms by
definition, although a persistent vulnerability for mood
dysregulation is always present. This persistent vulnerability has been hypothesized to result from over-reactive
emotional (i.e. anterior limbic) brain networks (Phillips
et al., 2003). If correct, this hypothesis suggests that, even
during euthymia, dysfunction within the anterior limbic
network persists, leaving patients at risk for mood and
cognitive disturbances (Strakowski et al., 2004). Wideranging deficits have been found in many studies of
juvenile bipolar disorder (Olvera et al., 2005; Bearden et al.,
2007). Persistent neuropsychological deficits present in
the euthymic state of bipolar affective disorder, particularly impairment in sustained attention, suggest that such
deficits could be vulnerability trait markers of the illness
(Thompson et al., 2005).
Aim
The aim of this work is to identify and assess the cognitive impairment of euthymic adolescents diagnosed
with bipolar disorder on neuropsychological measures of
DOI: 10.7123/01.EJP.0000411121.54126.e5
Cognitive functions in euthymic adolescents El Ray et al. 41
sustained attention, short-term memory, processing
speed and set shifting after exclusion of other comorbid
psychiatric disorders.
A total of 30 adolescents diagnosed with bipolar disorder type
I participated in this research. All the patients were selected
from the Kasr Al Aini adolescent outpatient psychiatric
clinic. Both male and female patients were included. They
were between the ages of 13 and 19 years, met the
Diagnostic and Statistical Manual of Mental Disorders
(DSM)-IV criteria for bipolar disorder type I and were
euthymic during application of the psychometric tools,
which was defined in our study as scores of 7 or below on
both the 17-item HRSD and the Young Mania Rating Scale.
All patients with comorbid psychiatric disorder, a history of
attention deficit hyperactivity disorder before the onset of
the disorder, intelligence quotient less than 90, any
neurological deficit or chronic illness, a history of significant
head trauma, electroconvulsive therapy in the past 6 months
or those who were illiterate were excluded. The control
group was selected to match the patients’ group for age, sex
and educational level. All control participants had no past
history of psychiatric or neurological disorders or family
history of psychiatric disorders. The diagnosis of bipolar
disorder type I as well as the exclusion of psychiatric co
morbidities and history of attention deficit hyperactivity
disorder starting before the onset of the bipolar disorder was
established by interviewing the patients and at least one of
their parents using the Kiddie Schedule for Affective
Disorders and Schizophrenia in school-aged children (KSADS-PL) (Kaufman et al., 1997). A written informed
consent was obtained from parents for their minor
adolescents and from the participants themselves if they
were aged 18 years or older.
Tools
Semistructural interview
A specially designed semistructural interview derived from
the Kasr Al Aini psychiatric sheet was used to cover demographic data, personal data, past history and family history.
The Kiddie Schedule for Affective Disorders and Schizophrenia
in school-aged children (Kaufman et al., 1997)
The K-SADS-PL is a semistructured diagnostic interview
designed to assess current and past episodes of psychopathology in children and adolescents according to DSMIII-R and DSM-IV criteria. Probes and objective criteria
are provided to rate individual symptoms. The K-SADSPL is administered by interviewing the parent(s), the
child and finally achieving summary ratings that include
all sources of information (parent, child, school). When
administering the instrument to preadolescents, the
parent interview should be conducted first. In working
with adolescents, the interview should be conducted first
with them, followed by the parent, which was followed in
our research. The majority of the items in K-SADS-PL are
scored using a 0–3-point rating scale. Score of 0 indicate
that no information is available; a score of 1 suggests that
the symptom is not present; a score of 2 indicates
subthreshold levels of symptomatology; and a score of 3
represents threshold criterion. The remaining items are
rated on a 0–2-point rating scale, in which 0 implies no
information; 1 implies that the symptom is not present;
and 2 implies that the symptom is present.
Hamilton Rating Scale for Depression (Hamilton, 1960)
The HRSD is the most widely used clinician-administered depression assessment scale. We have used the
17-item version, where a score of 0–7 is accepted to be
within the normal range or in clinical remission. It has
been used to ensure the euthymic state of cases after
interviewing them using the K-SADS-PL.
Young Mania Rating Scale (Young et al., 1978)
It is a clinician-rated scale used to rate the severity of
manic symptoms. The items rated are elevated mood,
increased motor activity, sexual interest, sleep, irritability,
speech and language, content of thought, disruptive or
aggressive behaviour, appearance and insight. Scoring of
each item is between 0 and 4 points. The cases had to
score 7 or less to be considered euthymic and thus to be
included in the study.
Letter cancellation test (Diller et al., 1974)
It is a measure of sustained attention (Ronald et al., 2000).
It has been applied in its Arabic version, where
participants were asked to cancel two fixed Arabic letters
whenever they found them amidst 19 rows of Arabic
letters, as fast as they could. The time in seconds taken
by each participant to complete this task was calculated.
Whenever any of the letters to be cancelled was missed,
this was considered an omission error. We used the Arabic
version by El Kholi (1985).
Digit span (Meleka and Ismail, 1996, 1999)
It is one of the subtests of both the adult and the child
Wechsler Intelligence Scale used to measure auditory
short-term memory. The candidate was asked to repeat a
dictated series of digits forward and another backward,
with two trials each time. The final score was calculated
by adding the score of the forward series to that of the
backward series.
Digit symbol coding (Meleka and Ismail, 1996, 1999)
It is one of the subtests of the Wechsler Intelligence Scale
used to measure processing speed (Doyle et al., 2005). In
the Arabic version of the Wechsler Intelligence Scale for
children that was applied with participants below 16 years,
the participants had to transcribe a digit symbol code as
quickly as possible for a duration of 2 min, whereas in the
adult version, used when participants were 16 years or
above, participants had to transcribe the digit symbol code
as quickly as possible for a duration of 90 s. The number of
correct transcriptions completed by the participant in the
given time was counted to yield the final score.
Bender gestalt test (Bender, 1938)
It is a measure of visual short-term memory and visual
motor maturity (McCarthy et al., 2002). It was formulated
by Lauretta Bender, a child neuropsychiatrist. The version
used in our study comprises six figures on six separate
cards. The cards were shown one after the other to each
participant, who was instructed to draw each figure
carefully, bearing in mind that he would be asked to recall
the six figures after about 2 min. Scoring was carried out
according to a standardized scoring system, where each
recalled figure would receive a score between 0 and 5
points according to the accuracy of the details recalled.
Table 2 Pattern of intake of psychotropic medication
Type of medication
Typical antipsychotic
Atypical antipsychotic
Antiepileptic drug
Lithium
SSRIs intake (fluoxetine)
Anticholinergic drug
% of negative intake
% of positive intake
23.3
56.7
10.0
93.3
93.3
43.3
76.7
43.3
90.0
6.7
6.7
56.7
Table 3 Neuropsychological test scores in both groups
Wisconsin card sorting test
Neuropsychological tests
The purpose of this test is to assess the ability to form
abstract concepts, to shift and maintain set and to utilize
feedback. The test is considered a measure of executive
function (Heaton et al., 1993) in that it requires strategic
planning, organized searching, the ability to use environmental feedback to shift cognitive set, goal-oriented
behaviour and the ability to modulate impulsive responding.
The test can be used with individuals aged 5 to 89 years.
The time required is about 15–30 min (Strauss et al., 2006).
The statistical methods
Statistical analysis was performed using the Statistical
Package of Social Science, version 16 (SPSS-V16, IBM,
Chicago, IL, USA). Descriptive analysis was performed using
frequency tests, pie and bar charts. The student’s unpaired ttest was used to compare quantitative data between two
groups and the analysis of variance and the post-hoc tests
were used to compare quantitative data between more than
two groups. The correlation between different quantitative
data was assessed using the Pearson correlation test. Finally,
the w2-test with Yates correction was used for the analysis of
categorical data. The level of significance was set at P less
than 0.05.
Results
53.3% of the cases were women and 46.7% were men. The
mean age of the cases was 18.03. The case and control
groups were matched in terms of age, sex and educational
level (P = 1, 1, 0.6, respectively) (Tables 1–4).
There were no statistically significant differences between cases with positive and negative intake of any of
the classes of psychotropic drugs used by the cases at the
time of assessment as regards the mean scores of the
neuropsychological tests.
Table 1 Clinical data of cases
Clinical data
HRSD
YMRS
Age of onset
Manic episodes
Depressive episodes
Hospitalization
Duration of illness
Mean
SD
N
0.4000
1.3667
14.9667
1.6667
0.7333
0.2667
3.0667
1.19193
1.67091
1.06620
0.88409
0.86834
0.44978
1.14269
30
30
30
30
30
30
30
HRSD, Hamilton Rating Scale for Depression; YMRS, Young Mania
Rating Scale.
Mean
Letter cancellation
Controls
30
75.5667
Cases
30
116.07
Omission errors in letter cancellation
Controls
30
0.0000
Cases
30
2.4667
Digit span
Controls
30
10.0000
Cases
30
8.3667
Digit symbol coding
Controls
30
51.1667
Cases
30
29.6333
Bender gestalt
Controls
30
19.9333
Cases
30
15.2667
Perseverative errors in WCST
Controls
30
3.5667
Cases
30
39.5333
SD
P
10.45741
25.44220
0.000
0.00000
3.54024
0.000
1.64002
1.44993
0.000
5.63293
9.33840
0.000
2.66437
3.05053
0.000
2.45909
13.23979
0.000
WCST, Wisconsin card sorting test.
Discussion
Our study aimed at assessing the performance of
euthymic adolescent patients with bipolar disorder on
neuropsychological measures of sustained attention, shortterm memory, processing speed and set shifting. The
comparison between the neuropsychological test scores of
our cases and controls revealed that the euthymic patients
showed poorer performance than controls in the letter
cancellation test, which is a measure of sustained
attention, with a highly significant statistical difference
between the mean scores of both groups on this test. This
is consistent with findings in the study conducted
by Kolur et al. (2006) and where euthymic bipolar patients
showed poorer performance than healthy controls on tests
of sustained attention. However, this finding is not
concordant with the study by DelBello et al. (2004),
where no statistically significant difference was found
between the performance of euthymic bipolar patients
and healthy controls in tests of sustained attention, but
this may be due to the small sample size in their study (10
cases and a matched control group).
The euthymic patients in our study also showed poorer
performance than controls on the digit span test, which is
a measure of auditory short-term memory, with a highly
significant difference between the mean scores of both
groups in this test. This finding is consistent with the
findings by Gruber et al. (2007), where euthymic bipolar
patients showed an impaired auditory short-term memory
in comparison with healthy controls. However, this finding
was in contrast to a recent study by Langenecker et al.
(2010), where euthymic patients showed no impairment
Cognitive functions in euthymic adolescents El Ray et al. 43
Table 4 Correlation between clinical data and neuropsychological test scores
Age of onset
Pearson’s correlation
P-value
Manic episodes
P-value
Depressive episodes
P-value
Hospitalization
P-value
Duration ff illness
P-value
Letter
cancellation
Omission
errors
Digit
span
– 0.086
0.650
0.443*
0.014
0.075
0.693
– 0.207
0.271
0.602**
0.000
– 0.254
0.176
Digit
symbol
BG
Perseverative
errors
0.078
0.681
– 0.061
0.750
– 0.304
0.102
0.152
0.421
0.043
0.821
– 0.196
0.299
– 0.011
0.955
0.199
0.292
– 0.194
0.305
– 0.289
0.122
– 0.076
0.688
0.289
0.122
0.258
0.169
– 0.146
0.442
– 0.049
0.796
0.008
0.968
– 0.305
0.101
– 0.146
0.440
– 0.027
0.886
0.077
0.685
0.089
0.641
– 0.253
0.178
0.084
0.660
0.098
0.607
BG, bender gestalt test.
*Statistically significant.
**High statistical significance.
in auditory memory ability, although the sample size in
the latter was larger.
Moreover, the patients in our study showed poorer
performance than controls in the Bender gestalt test,
which is a measure of visual short-term memory, also with a
statistically significant difference between both groups.
This is concordant with the study by Langenecker et al.
(2010) but is inconsistent with the study by Pavuluri et al.
(2006), where there was no difference between euthymic
patients and controls as regards visual short-term memory.
In addition, the cases and controls in our study showed a
statistically significant difference between their mean
scores on the digit symbol coding test, where cases showed
a poorer performance, revealing impairment in mental
processing speed. This finding is consistent with the
findings obtained in a study conducted by Langenecker
et al. (2010).
Regarding the performance on the Wisconsin card sorting
test, the patients in our study committed more perseverative errors than controls, with a statistically significant
difference, which revealed a deficit in set shifting ability in
cases. This finding is in agreement with the findings in the
study by Trivedi et al. (2007), where euthymic patients
committed more perseverative errors than healthy controls
on the Wisconsin card sorting test, also with a statistically
significant difference between both groups.
As for the correlation between the clinical variables and
the mean neuropsychological scores of the patients in our
study, the number of manic episodes was positively
correlated to the mean number of omission errors in the
letter cancellation test, which is statistically significant
(i.e. the number of manic episodes was negatively
correlated to the sustained attention function of the
euthymic patients in our study).This is consistent with
the findings in the study by Clark et al. (2002), where
sustained attention performance suffered with increasing
burden of manic episodes.
In our study, the age of illness onset, like the number of
manic episodes, was positively correlated to the mean
number of omission errors on the letter cancellation test,
which is consistent with the finding obtained by Martinez
Aran et al. (2004b), where the age of onset of illness was also
positively correlated to a score on a measure of sustained
attention (i.e. those with a later onset of illness performed
more poorly on measures of sustained attention).
In our study, no statistically significant correlation was
found between the duration of illness and any of the
neuropsychological test scores, which was concordant with
a study assessing the same neuropsychological functions in
euthymic bipolar patients (Kolur et al., 2006).
As regards the number of depressive episodes, no
significant correlation was found between the number
of depressive episodes and any of the neuropsychological
scores in our study, which is in agreement with the
findings obtained in the study conducted by Martinez
Aran et al. (2004b), where no significant correlation was
found between the number of depressive episodes and scores
on measures of verbal memory and sustained attention.
Moreover, no significant correlation was found between
the number of hospitalizations and any of the neuropsychological scores in our study, which is similar to the
findings obtained by Cavanagh et al. (2002), where no
significant relationship was found between the total
number of hospitalizations and executive function,
psychomotor speed and visual recognition. It is also
concordant with the finding obtained by Clark et al.
(2002), where no significant relationship was found
between the total number of hospital admissions and
measures of sustained attention, set shifting, verbal
memory and speed of information processing. Moreover,
this similarity was present despite the fact that these two
studies included patients of an older age group than those
in our study, with more number of hospitalizations.
As for the intake of psychotropic medication, no statistically significant difference was found between cases with
positive and negative intake of typical antipsychotics,
atypical antipsychotics, antiepileptics, anticholinergic
drugs and antidepressants as regards neuropsychological
44
test scores, which are consistent with the finding in the
study by Kolur et al. (2006). Moreover, there was no
statistically significant difference between cases with
positive and negative intake of lithium as regards
neuropsychological test scores, which is similar to the
finding in the study conducted by Martinez Aran et al.
(2004a) and also by Kolur et al. (2006).
Limitations
Our study was cross sectional, whereas longitudinal
studies can track the decline in neuropsychological
function with illness progression better and can also track
the impact of medication on cognition more accurately.
Our study was not drug free; although no significant
relationship was found between psychotropic drug intake
and neuropsychological test scores in our study and
similar others, yet, the effect of psychotropic drugs on
cognition cannot be excluded. However, for euthymia to
be established, being drug free is quite a remote
possibility; moreover, it gives rise to ethical issues.
Acknowledgements
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Original article 45
Quality of life and burden of women with premenstrual
dysphoric disorder
Nagda M. El-Masry and Nelly R. Abdelfatah
Department of Psychiatry, Faculty of Medicine, Zagazig
University, Zagazig, Egypt
Correspondence to Nagda El-Masry, Lecturer of
Psychiatry, Faculty of Medicine, Zagazig University,
Zagazig, Egypt
Tel: + 012 234 8839; fax: + 055 230 7830;
Received 3 January 2011
Accepted 14 May 2011
Background
Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual physical
and psychological discomfort. The disorder is common and has a negative impact on
mental health and quality of life of women suffering from PMDD.
Aim
This study was carried out to evaluate the quality of life of women with PMDD.
In a comparative case–control study, 34 patients with PMDD and 34 healthy controls
(matched for age, educational level, and social class) were included. All were within
the reproductive period.
Tools
Both groups were subjected to the following psychometric tools: a semistructured
interview, a structured clinical interview for the Diagnostic and Statistical Manual of
Mental Disorders-fourth edition, the World Health Organization Quality Of Life
instrument, the symptom checklist instrument, the psychological adjustment scale, and
the Sheehan disability scale.
Results
Patients and control groups were matched for age (P = 0.46), marital status (P = 0.35),
educational level (P = 0.87), and socioeconomic status (P = 0.84). The mean scores of
psychological and social relationships domains on the World Health Organization
Quality of Life (WHOQOL)-BREF were lower for patients compared with the healthy
control participants. Differences were statistically significant for emotional, family, and
social adjustment (Po0.001). There were statistically significant differences for
somatization, obsessive-compulsive, depressive, and anxiety symptoms (Po0.001).
The burden of PMDD was higher for the patient group compared with the healthy
control participants (Po0.001). The family responsibilities domain was the most
affected on the Sheehan disability scale.
Conclusion
Patients with PMDD have lower quality of life than healthy participants. They have
maladjusted emotions, family relations, and social functioning. They experience higher
somatization, obsessive-compulsive, depressive, and anxiety symptoms than normal
participants. The burden of illness is high. Appropriate recognition of the disorder and
its impact should lead to the treatment of women with PMDD. Effective treatments
are available. They should reduce individual suffering and impact on families, society,
and economy.
Keywords:
burden, premenstrual dysphoric disorder, quality of life
1110-1105
Introduction
Premenstrual dysphoric disorder (PMDD) is a severe
form of premenstrual physical and psychological discomfort occurring 1 to 2 weeks before menstruation (Dante
and Facchinetti, 2011). The symptoms usually disappear
shortly after the onset of menses (Futterman and Rapkin,
2006; Campagne and Campagne, 2007).
The prevalence of PMDD, where premenstrual symptoms reach a level of severity that interferes with
personal, social, and professional functioning, is about
3–8% (Cohen et al., 2002; Halbreich et al., 2003;
Steiner et al., 2003; Di Giulio and Reissing, 2006).
PMDD most likely has multiple determinants in
the biological, physiological, and sociocultural domains
(Stanton et al., 2002).
Although the etiology of PMDD is unknown, the
symptoms of dysphoria, including depression and anxiety,
have been associated with serotonergic dysregulation
(Ivezić et al., 2010).
DOI: 10.7123/01.EJP.0000411124.67583.a3
46
Some potential risk factors for PMDD are the quality of
interpersonal relationships and cooperation, self-esteem,
expectation, and perception of premenstrual symptoms,
stress, socioeconomic factors, biological factors, and
lifestyle factors (Deuster et al., 1999).
Matsumoto et al. (2007) suggested that altered functioning of the autonomic nervous system in the late luteal
phase could be associated with diverse psychosomatic and
behavioral symptoms appearing premenstrually.
Landen et al. (2004) have reported that PMDD may be
associated with reduced vagal tone compared with
controls and that this difference is most apparent in the
nonsymptomatic follicular phase of the menstrual cycle.
PMDD, first called the late luteal phase dysphoric
disorder, was included as a provisional diagnostic category
in the appendices of the Diagnostic and Statistical Manual of
Mental Disorders (DSM)-III-R (American Psychiatric
Association, 1987). It remained as an appendix in DSM-IV,
after being renamed PMDD (American Psychiatric
Association, 1994).
The most prevalent symptoms include irritability, mood
lability, depression, anxiety, impulsivity, feeling of ‘loss of
control,’ fatigue, decreased concentration, abdominal
bloating fluid retention, breast swelling, and general
aches (Kessel, 2000).
According to the American psychiatric association (DSMIV), PMDD criteria require five or more of the following
symptoms to be present premenstrually: depressed mood
or dysphoria, anxiety or tension, affective lability, irritability, decreased interest in usual activities, concentration
difficulties, marked lack of energy, marked changes in
appetite, overeating or food cravings, hypersomnia or
insomnia, feeling overwhelmed, and other physical
symptoms, for example, breast tenderness, bloating. At
least one of these symptoms must be a mood symptom,
that is: depressed mood or dysphoria, anxiety or tension,
affective lability, or irritability. In addition, certain
phenomenal characteristics are required (present premenstrually, absent postmenstrually, causing premenstrual interference other than an exacerbation of another
disorders). PMDD was confirmed if, throughout the
entire week before menstruation, at least one of the four
core symptoms (depressed mood, anxiety or tension,
affective liability, anger, or irritability) was reported as
severe, and at least four additional symptoms (for a total
of five) as moderate to severe, and if they were absent in
the week after menses (Halbreich et al., 2007).
PMDD can lead to disruption in interpersonal relationships and role functioning. Recent studies of the burden
of illness of PMDD have identified a high economic
indirect cost, mostly from reduced productivity and
effectiveness at work, in addition to disturbed parenting
and marital relationships (Pearlstein and Steiner, 2008).
The impairment and lowered quality of life is similar to
that of dysthymic disorder and is not much lower than
major depressive disorder. Appropriate recognition of the
disorder and its impact should lead to the treatment of
more women with premenstrual syndrome (PMS) and
PMDD (Halbreich et al., 2003).
PMDD is commonly associated with other mood-related
disorders such as major depression and causes significant
life impairment (Sassoon et al., 2011).
Aim
This study was carried out to evaluate quality of life of
women with PMDD.
This comparative case–control study was conducted at the
psychiatry outpatient clinic of Zagazig University hospitals
from April 2010 till September 2010. It included 34 female
patients compared with 34 healthy women, recruited from
among employees and visitors of the hospital.
All patients were diagnosed as having PMDD according to
DSM-IV TR (American Psychiatric Association, 2000).
Inclusion criteria
Good general health, euomenorrhea, lack of major uterine
dysfunction, reproductive age (18–45), informed consent.
Exclusion criteria
General medical illness (diabetes mellitus, hypothyroidism, anemia, seizure disorders, past or present history of
other psychiatric disorder, use of oral contraceptives).
Both patients and controls were subjected to the
application of case history of the psychiatry department
of Zagazig university hospitals to obtain sociodemographic and relevant clinical data.
A structured clinical interview for DSM-IV axis-I
disorders was used for all cases to confirm the diagnosis
and also to screen the control participants for PMDD
(First et al., 1995).
The following psychometric tools were applied to both
patients and controls:
(1) World Health Organization Quality Of Life (WHOQOL)-BREF (The WHOQOL group, 1996): is a
standardized comprehensive instrument for assessment of quality of life comprising of 26 items and was
developed by WHO. The scale provides a measure of
an individual’s perception of quality of life for four
domains: (a) physical health (seven items), (b)
psychological health (six items), (c) social relationships (three items), and (4) environmental health
(eight items). In addition, it also includes two
questions of overall quality of life and general health
factors. The domain scores are scaled in a positive
direction (i.e. higher scores denote higher quality of
life). The range of scores is 4–20 for each domain.
The international consistency of WHOQOL-BREF
ranged from 0.66 to 0.87 (Chronbach’s a coefficient).
The scale had been found to have good discriminant
validity. It has good test–retest reliability and is
The burden of premenstrual dysphoric disorder El-Masry and Abdelfatah 47
recommended for use in health surveys and to assess
the efficacy of any intervention at suitable intervals
according to the need of the study. The first
transformation method converts scores to range
between 4 and 20; the second transformation method
converts domain scores to a 0–100 scale.
(2) Symptoms checklist-90-revised (SCL-90R) (Derogatis,
1983): this 90-item self-report instrument measures
nine dimensions of psychological symptoms and yields
three global indexes of distress. The measured
dimensions are somatization, obsessive-compulsive,
interpersonal sensitivity, depression, anxiety, hostility
phobia, paranoid ideation, and psychoticism. Participants were instructed to indicate how much distress
each item on the SCL-90R had caused on a five-point
scale ranging from (0 = not at all to 4 = extremely). In
this study, we used the Arabic form (Al-Behairy, 1984).
In this study, we used the somatization, obsessivecompulsive, depression, and anxiety subscales to assess
these symptoms among the studied women.
(3) Psychological Adjustment scale (Shokeer, 2003): it
consists of 80 items that measure four dimensions of
adjustment: (a) emotional adjustment, (b) health
adjustment, (c) family adjustment, and (4) social
adjustment. Participants were tested on a three-point
scale ranging from (0 = not at all to 2 = extremely).
(4) Sheehan disability scale (Sheehan et al., 1996): was
developed by Sheehan to assess functional impairment in three interrelated domains: work/school,
social life and home life, or family responsibilities are
impaired by his or her symptoms on a 10-point visual
analogy scale. The numerical ratings of 0–10 can be
translated into a percentage. The three items can
also be summed into a single dimensional measure
of global functional impairment that ranges from
0 (unimpaired) to 30 (highly impaired).
Statistical analysis
Data were collected, revised, and analyzed statistically
using SPSS (Statistical Package for Social Science, version
15, IBM, Chicago, IL, USA). Data were described by
frequency and percentage for qualitative data, and mean
and SD for quantitative data. The w2-test was used to
determine the relationship between two qualitative
variables. Student’s t-test was used for comparing
quantitative variables. Probability level (Po0.05) was
considered statistically significant.
Results
Table 1 illustrates the characteristics of both patients
with PMDD and the control participants. The study
included 34 patients with PMDD and 34 control
participants. Both groups had similar demographic and
socioeconomic characteristics. The majority of the
studied patients and control participants were married
(61.8 and 64.7%, respectively), lived in an urban area
(52.9 and 58.8%, respectively), and had received secondary school education (58.8 and 61.8%, respectively).
Table 1 Characteristics of patients with premenstrual dysphoric
disorder and the control participants
Variables
Age
18–30
31–45
Marital status
Single
Married
Divorced
Residence
Urban
Rural
Educational level
Primary
Secondary
University
Employment status
Employed
Unemployed
Student
Type of work
Manual
White collar
Socioeconomic status
Low
Moderate
High
History of pregnancy
Menarche (years)
Duration of menstrual
cycle (days)
Duration of menstruation
(days)
PMDD
(N = 34)
Control
(N = 34)
Test of
significance
No (%)
No (%)
w2
P-value
16 (47.1)
18 (52.9)
19 (55.9)
15 (44.1)
0.53
0.46
11 (32.4)
21 (61.8)
2 (05.8)
12 (35.3)
22 (64.7)
0 (0.0)
2.07
0.35
18 (52.9)
16 (47.1)
20 (58.8)
14 (41.2)
0.24
0.62
2 (5.9)
20 (58.8)
12 (35.3)
3 (08.8)
21 (61.8)
10 (29.4)
0.41
0.81
16 (47.0)
10 (29.4)
6 (17.6)
23 (67.6)
3 (8.8)
8 (23.6)
5.26
0.07
26 (76.5)
8 (23.5)
25 (73.5)
9 (26.5)
0.08
0.77
2 (5.9)
24 (70.6)
8 (23.5)
20 (58.8)
Mean ± SD
13.6 ± 3.2
26.1 ± 6.1
3 (8.8)
22 (64.7)
9 (26.5)
21 (61.7)
Mean ± SD
12.9 ± 2.4
29.2 ± 5.3
0.35
0.84
0.06
t
1.0
1.5
0.8
P-value
0.31
0.11
6.9 ± 2.1
5.1 ± 1.6
3.97 o0.001*
PMDD, premenstrual dysphoric disorder.
*Po0.05 is statistically significant.
47.0% of the patients and 67.6% of the control
participants were employed.
Majority of both groups were employed: 47.0% of the
patients and 67.6% of the control participants. 58.8% of the
patients and 61.7% of the control participants had a history
of pregnancy. 70.6% of patients and 64.7% of control
subjects were of moderate socioeconomic status.
They were matched as regards age (w2 = 0.53, P = 0.46),
marital status (w2 = 2.07, P = 0.35), residence (w2 = 0.24,
P = 0.62), educational level (w2 = 0.41, P = 0.81), employment status (w2 = 5.26, P = 0.07), and type of work
(w2 = 0.08, P = 0.77).
Socioeconomic status (w2 = 0.35, P = 0.84) and history of
pregnancy (w2 = 0.06, P = 0.8).
No statistically significant difference was found between
the PMDD group and the control group regarding
menarche (P = 0.31) and the duration of the menstrual
cycle (P = 0.11), whereas there was a statistically
significant difference between the two groups regarding
the duration of menstruation (days) (P = 0.001).
Table 2 illustrates the mean and SD of WHOQOL-BREF
applied to the studied groups. There was no statistically
significant difference between PMDD and control groups as
regards the physical domain of WHOQOL-BREF (t = 0.73,
48
Table 2 World Health Organization Quality Of Life-BREF:
comparison between premenstrual dysphoric disorder and
control groups
Domain
Physical
domaina
Psychological
domaina
Social
relationshipsa
Environmenta
PMDD group
(No = 34)
Mean ± SD
Control group
(No = 34)
Mean ± SD
t
P-value
53.4 ± 8.1
55.2 ± 9.8
0.73
0.6
44.6 ± 9.3
71.5 ± 13.2
9.5
o0.001*
55.8 ± 8.7
67.2 ± 12.1
4.46 o0.001*
52.8 ± 8.1
51.7 ± 9.3
0.52
0.5
a
Score range from 0 to 100.
P = 0.6). There was a statistically significant difference
between the PMDD group and the control group regarding
the psychological domain (t = 9.5, Po0.001). Also, there
was a highly statistically significant difference between the
two groups regarding social relationship (t = 4.46,
Po0.001), whereas no statistically significant difference
was found between the two groups regarding the environmental domain. The social relationships domain was the
most affected domain between the four domains of
WHOQOL-BREF.
Table 3 shows the mean and SD of the psychological
adjustment scale applied to the PMDD and the control
groups. There was a highly statistically significant difference
between the two groups regarding emotional adjustment
(t = 19.23, Po0.001), whereas no statistically significant
difference was detected between the two groups regarding
the health adjustment domain (t = 1.38, P40.05). There
was a statistically significant difference between the two
groups regarding family adjustment (t = 10.31, Po0.001)
and social adjustment (t = 10.92, Po0.001).
Table 4 shows the mean and SD of the SCL-90R scale
applied to the PMDD group and the control group. We
used somatization, obsessive-compulsive, depression, and
anxiety domains to assess the symptoms of these groups
among the studied women.
We found highly statistically significant differences
between the two groups regarding somatization
(t = 24.91, Po0.001), the obsessive-compulsive domain
(t = 8.69, Po0.001), the depression domain (t = 18.25,
Po0.001), and the anxiety domain (t = 22.6, Po0.001).
The depression domain was the most affected domain.
Table 5 shows the mean and SD of the Sheehan disability
scale applied to the PMDD and the control groups. Highly
statistically significant differences were found between the
two groups regarding work (t = 7.44, Po0.001), social/
leisure activities (t = 3.18, Po0.001), and family responsibilities (t = 12.09, Po0.001). The most affected area of
functioning was family responsibilities.
Discussion
Five percent of menstruating women meet the criteria for
PMDD and about 20% of them have ‘subthreshold
PMDD’ or severe PMS. Thus, in each menstrual cycle,
Table 3 Psychological adjustment scale: comparison between
premenstrual dysphoric disorder and control groups
Domain
Emotional
adjustmenta
Health adjustmenta
Family adjustmenta
Social adjustmenta
PMDD group Control group
(No = 34)
(No = 34)
Mean ± SD
Mean ± SD
t
P-value
15.3 ± 4.1
38.2 ± 5.6
19.23 o0.001*
14.4 ± 5.4
11.7 ± 6.8
12.1 ± 4.3
16.4 ± 6.4
30.4 ± 8.1
31.3 ± 9.3
1.38 40.05
10.31 o0.001*
10.93 o0.001*
a
score range from 0 to 40.
Table 4 Symptoms checklist-90R scale: comparison between
Domain
Somatizationa
Obssesivecompulsiveb
Depressionc
Anxietyd
PMDD
group
(No = 34)
Mean ± SD
Control
group
(No = 34)
Mean ± SD
28.7 ± 3.1
18.4 ± 5.3
12.2 ± 2.3
9.9 ± 2.1
24.91 o0.001*
8.69 o0.001*
31.2 ± 6.4
21.6 ± 3.4
8.8 ± 3.2
6.1 ± 2.1
18.25 o0.001*
22.6 o0.001*
t
P-value
a
b
c
Score range from 0 to 52
d
Table 5 Sheehan disability scale: comparison between
Domain
Work
Social/leisure
activities
Family responsibilities
Total score
PMDD
group
(No = 34)
Mean ± SD
Control
group
(No = 34)
Mean ± SD
7.31 ± 2.3
6.34 ± 2.4
3.5 ± 1.9
4.6 ± 1.2
7.44 o0.001*
3.18 o0.001*
9.12 ± 3.1
22.77 ± 5.1
2.3 ± 1.1
10.4 ± 3.1
12.09 o0.001*
12.11 o0.001*
t
P-value
The total score ranges from 0 (unimpaired) to 30 (highly impaired).
1 in 4 women has emotional, behavioral, and physical
premenstrual symptoms that can lead to disruption
in interpersonal relationships and role functioning
(Pearlstein and Steiner, 2008).
Our study revealed that the quality of life of women with
PMDD was severely affected as there were statistically
significant differences between the two groups regarding
domains of psychological and social relationships. This
finding is in agreement with other studies. Women with
confirmed PMS and PMDD reported significantly lower
quality of life, increased absenteeism from work,
decreased work productivity, impaired relationships
with others, and increased visits to health providers
(Borenstein et al., 2003; Steiner et al., 2003; Dean and
Borenstein, 2004; Kornstein et al., 2005). The impairment
The burden of premenstrual dysphoric disorder El-Masry and Abdelfatah 49
and lowered quality of life for PMDD is similar to that of
dysthymic disorder and is not much lower than major
depressive disorder (Halbreich et al., 2003).
The length of menstruation was reported to be associated
with PMDD in studies by Adewuya et al. (2008) and Kaur
et al. (2004). This result is in agreement with our results
as there was a statistically significant difference between the
PMDD group and the control group (t = 3.97, Po0.001).
This factor may lead to impairment of quality of life.
Emotional, family, and social adjustment were assessed
using the psychological adjustment scale. We found a highly
statistically significant difference between the two groups
(Po0.001). This maladjustment is in agreement with many
studies. Anxiety, irritability, and mood lability are associated
with functional impairment (Bloch et al., 1997; Angst et al.,
2001; Pearlstein and Steiner 2008; Ivezić et al., 2010).
PMDD patients have lower quality of life than healthy
controls. They have maladjusted emotions, family relations, and social functioning. Also, they have higher scores
of somatization, obsessive-compulsive, depressive, and
anxiety symptoms than healthy controls. The burden of
illness was high mostly as a result of reduced productivity
and effectiveness at work and disturbed parenting and
marital relationships. Thus, appropriate recognition of the
disorder and its impact should lead to treatment of more
women with PMDD. Efficacious treatments are available.
They should reduce individual suffering and impact on
families, society, and economy.
Acknowledgements
PMDD causes marked social impairment during the last
half of the menstrual cycle (Kaur et al., 2004).
We found a highly statistically significant difference
between the two groups regarding somatization symptoms of the SCL-90R scale (t = 24.91, Po0.001). This
result is in agreement with those of Halbreich et al.
(2007), who reported that some cultures emphasize
somatic rather than emotional premenstrual symptoms.
Obsessive-compulsive symptoms were found to be higher
in patients with PMDD compared with control participants (Po0.001). Sasson and his colleagues found that
obsessive-compulsive personality disorder was the most
common character pathology in the PMS (18%). We also
found that depressive symptoms were present with a
statistically significant difference in women with PMDD
compared with control participants (t = 18.25, Po0.001).
This result is in agreement with studies by Kessel (2000)
and Halbreich et al. (2007). Major depressive disorder is
one of the most common axis I psychiatric disorders that
may be concurrent and exacerbated premenstrually
(Wittchen et al., 2002).
The current study found that anxiety symptoms were more
prevalent in patients than in control participants (t = 22.6,
Po0.001). Generalized anxiety disorder is one of the most
common axis I psychiatric disorders that exacerbate
premenstrually (Hsiao et al., 2004; Kim et al., 2004).
The Sheehan disability scale was used to assess the
burden of PMDD among the studied patients. There was
a statistically significant difference between the two
groups regarding work, social/leisure activities, and family
responsibilities (Po0.001). The burden of illness of
PMDD results from the severity of symptoms, the
chronicity of the disorder, and impairments in work,
relationships, and activities (Freeman, 2005; Di Giulio
and Reissing, 2006).
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Egyptian Journal of Psychiatry

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