Grundläggande begrepp
Transcription
Grundläggande begrepp
2014-‐10-‐03 Djurmodeller i neuropsykiatrisk forskning Jakob Näslund, 141003 Föreläsningsupplägg • I: Grundläggande begrepp • II: A= studera psykisk sjukdom i djur • III: Forskningsexempel Föreläsningsupplägg 1 2014-‐10-‐03 Grundläggande begrepp Validitet • Framförallt begrepp som används inom psykometri (mätning av psykologiska/psykiatriska fenomen), där svar måste tolkas och sä=as i kontext • Många olika aspekter Grundläggande begrepp: validitet 2 2014-‐10-‐03 Validitet; djurmodeller • Uppenbar eller direkt validitet (eng. ’face validity’) – hur väl verkar testet mäta vad man vill mäta • Predik/v validitet – hur väl kan man förutsäga exempelvis beteende i annat test eller svar på läkemedel uSfrån testet • Konstruktvaliditet – hur väl mäter testet egentligen det man vill mäta; svårt a= veta! Grundläggande begrepp: validitet Validitet; djurmodeller BJP CA Jones et al. Figure 1 Schematic diagram of the key behavioural, neurochemical and structural changes expected be present and to have translational relevance to the three core symptom domains of schizophrenia in an animal model of the disorder. application of some of the common models with emphasis on their predictive validity to evaluate novel compounds that could improve the cognitive and negative symptoms seen in schizophrenia. Recently, it has been estimated that over 20 different animal models of schizophrenia have been developed (Carpenter and Koenig, 2008), although several have considerable overlap in the methodology/principle used, and all fit into four different induction categories: developmental, druginduced, lesion or genetic manipulation, as will be discussed in this review. Initial animal models were developed on the basis of the tenet theory that dopamine dysfunction was central to the pathophysiology of schizophrenia, but with increased understanding of the genetic basis and potential involvement of glutamate animal models have also been developed to explore their involvement in the disorder. Most rodent models of schizophrenia tend to replicate aspects of the positive symptoms of schizophrenia (Table 1), such as hyperactivity probably reflecting enhanced mesolimbic dopamine function, but some, including methylazoxymethanol (MAM), neonatal hippocampal lesion, isolation rearing Grundläggande begrepp: validitet 1164 British Journal of Pharmacology (2011) 164 1162–1194 from weaning and chronic phencyclidine (PCP) administration, show cortical dopaminergic dysfunction and sensorimotor gating deficits that may be the consequence of altered development of frontal cortical–limbic circuits. Treatment of the negative and cognitive symptoms of schizophrenia is a vital and unmet clinical need that could have a major impact on patient recovery and re-integration into society. Therefore, the development of more comprehensive models that more adequately replicate deficits in these symptoms and help to understand causal factors is ongoing, but many of the models remain to be tested, as reviewed herein. Neurodevelopmental models Human epidemiology provides compelling evidence that exposure of the neonate, either during gestation or the perinatal period, to adverse environmental insults increases the risk of developing schizophrenia. Thus, maternal stress, malnutrition, infection or immune activation, or obstetric complications (such as hypoxia) during birth are just some of 3 2014-‐10-‐03 Några användbara begrepp • Fitness – förmåga a= reproducera sig och få livskraVig (reproducerande) avkomma • Homologi – gen/struktur/beteende i två olika djur som utvecklats från samma gen/struktur/ beteende i en anfader • Livshistoria – bre= begrepp för hur e= djurs liv ser ut, antal ungar, livslängd, rovdjurstryck osv. men även fysiologiska parametrar som immunsvar Grundläggande begrepp: ordlista Några användbara begrepp • Endofenotyp – del av en större fenotyp (anhedoni i depression, exempelvis) • Patognomon – e= patognomont symptom/ tecken/labfynd är unikt för en viss sjukdom Grundläggande begrepp: ordlista 4 2014-‐10-‐03 Vad kan en modell vara? • E= enskilt (beteende)test • Djur som utsa=s för viss behandling/kirurgiskt ingrepp • En avlad stam • GeneSskt modifierade djur (e= fåtal monogena sjukdomar dock och få entydigt vikSga gener i andra) Grundläggande begrepp: modeller Vilka djur använder man? • Gnagare (rå?or, möss, hamstrar) • Mer ovanliga djur – Kaniner – Makaker – Spetsekorrar – Zebrafisk Grundläggande begrepp: modeller 5 2014-‐10-‐03 Vilka djur använder man? • Det finns fällor! Exemplet sexuell dimorfism i beteende: Journai of Personality and Social Psychology 2001, Vol. 81, No. 2,322-331 In the public domain DOI: 10.1037//0022-3514.81.2.322 Gender Differences in Personality Traits Across Cultures: Robust and Surprising Findings Paul T. Costa Jr., Antonio Terracciano, and Robert R. McCrae National Institute on Aging, National Institutes of Health Secondary analyses of Revised NEO Personality Inventory data from 26 cultures (N = 23,031) suggest that gender differences are small relative to individual variation within genders; differences are replicated across cultures for both college-age and adult samples, and differences are broadly consistent with gender stereotypes: Women reported themselves to be higher in Neuroticism, Agreeableness, Warmth, and Openness to Feelings, whereas men were higher in Assertiveness and Openness to Ideas. Contrary to predictions from evolutionary theory, the magnitude of gender differences varied across cultures. Contrary to predictions from the social role model, gender differences were most pronounced in European and American cultures in which traditional sex roles are minimized. Possible explanations for this surprising finding are discussed, including the attribution of masculine and feminine behaviors to roles rather than traits in traditional cultures. Grundläggande begrepp: modeller Gender differences in personality traits have been documented in many empirical studies.1 Maccoby and Jacklin (1974) conducted the first major review of research on sex-related differences in cognition, temperament, and social behavior in children and adults. They concluded that men are more assertive and less anxious than women; no differences were found for two other traits analyzed, locus of control and self-esteem. Feingold (1994) used meta-analysis to confirm the gender differences in adult personality traits reported by Maccoby and Jacklin (1974) and explored other gender differences in normative data from the most widely used personality inventories. He concluded that women scored lower than men on assertiveness and higher on gregariousness (extroversion), anxiety, trust, and tendermindedness (nurturance). Feingold (1994) organized his review in terms of the five broad factors and 30 specific facets of the Revised NEO Personality Inventory (NEO-PI-R; Costa & McCrae. 1992). As a comprehen- sive guide to personality traits, that model can provide the basis for a systematic examination of gender differences in personality. Unfortunately, from the available data, Feingold was only able to conduct reviews of nine traits. In this article, we provide new data that allow an examination of gender differences in all 30 traits assessed by the NEO-PI-R, and thus offer a more complete account of gender differences in personality. Broad Themes in Gender Differences The NEO-PI-R is an operationalization of the Five-Factor Model (FFM), which structures specific traits in terms of five broad factors. It is possible to summarize known gender differences in terms of the FFM, although the summary is not completely straightforward. Previously reported gendef differences appear to be associated with Neuroticism (N), the dimensions of the Interpersonal Circumplex (Wiggins, 1979), and variations within the domain of Openness to Experience (O). Måste sä=as i relaSon Sll det mänskliga Sllståndet! Neuroticism (N) Paul T. Costa Jr., Antonio Terracciano, and Robert R. McCrae, National Institute on Aging, National Institutes of Health, Baltimore, Maryland. N is a broad domain of negative affect, including predispositions Portions of this article were presented as part of the symposium, Crossto experience anxiety, anger, depression, shame, and other disCultural Perspectives on Gender Differences in Personality Traits, pretressing emotions. Gender differences on traits related to N have sented at the Second Annual Meeting of the Society for Personality and been consistently reported, with women scoring higher than men Social Psychology, February 2001, San Antonio, Texas. (Lynn & Martin, 1997). Feingold (1994) found that women scored For providing unpublished data analyzed here, we thank Filip De Fruyt, higher in anxiety; Nolen-Hoeksema (1987), in a review of general Ivan Mervielde, Hans Hoekstra, Wayne Parker, Jiiri Allik, Talvi KallasBiological Psychology 88 (2011) 13–19 population surveys, reported that women scored higher in sympmaa, Anu Realo, Gregorio del Pilar, A. Timothy Church, Marcia Katigbak, Jean-Pierre Rolland, Jean-Michel Petot, Fritz Ostendorf, Alois Angleitner, toms of depression; and Kling, Hyde, Showers, and Buswell Lena Halim, Gian-Vittorio Caprara, Claudio Barbaranelli, Savita lists Deo, available at ScienceDirect Contents P. H. Lodhi, Hilmar Nordvik, 0yvind Martinsen, Margarida Pedrosa de 1 Lima, Ralph L. Piedmont, Maria Avia, Jesus Sanz, Maria SanchezAs the American Psychological Association Publication Manual (4th Bernardos, Goran Knezevic, B. Radovic, and Thomas Martin. ed.; American Psychological Association, 1994) states, gender is cultural and sex is biological; whether the differences at issue in this article are Correspondence concerning this article should be addressed to Paul T. cultural or biological (or both) is as yet unresolved. We use gender Costa Jr., Box #03, Laboratory of Personality and Cognition, Gerontology j o uNational r n a l h Institutes o m e p a of g eHealth, : w w w . e ldifferences s e v i e r . c because o m / l o cthat a t eterm / b i owas p s yused c h oin the latest major review of the Research Center, National Institute on Aging, topic (Feingold, 1994), but we do not wish to imply that we consider 5600 Nathan Shock Drive, Baltimore, Maryland 21224-6825. Electronic personality differences to be cultural in origin. mail may be sent to [email protected]. Biological Psychology 322 Is there tonic immobility in humans? Biological evidence from victims of traumatic stress Eliane Volchan a,∗ , Gabriela G. Souza b , Camila M. Franklin a , Carlos E. Norte a , Vanessa Rocha-Rego a , Jose M. Oliveira a , Isabel A. David c , Mauro V. Mendlowicz c , Evandro Silva Freire Coutinho d , Adriana Fiszman e , William Berger e , Carla Marques-Portella e , Ivan Figueira e a Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Departamento de Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Brazil Universidade Federal Fluminense, Niterói, Brazil Escola Nacional de Saúde Publica, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil e Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil b c d a r t i c l e i n f o Article history: Received 11 November 2010 Accepted 6 June 2011 Available online 5 July 2011 a b s t r a c t Tonic immobility, characterized by profound motor inhibition, is elicited under inescapable threat in many species. To fully support the existence of tonic immobility in humans, our aim was to elicit this reaction in a laboratory setting and measure it objectively. To mimic exposure to life-threatening events in the lab, trauma-exposed participants with PTSD (n = 18) and without PTSD (n = 15) listened to the script of their autobiographical trauma. Posturography and electrocardiography were employed. Reports of script-induced immobility were associated with restricted area of body sway and were correlated with accelerated heart rate and diminished heart rate variability, implying that tonic immobility is preserved in humans as an involuntary defensive strategy. Immobility reports seemed more evident in PTSD, suggesting that, in some patients, tonic immobility may be elicited during re-experiencing episodes in daily life. This study provided a measure of tonic immobility, a peritraumatic reaction for which cumulative clinical evidence had linked to the severity of PTSD. © 2011 Elsevier B.V. All rights reserved. Grundläggande begrepp: modeller Keywords: Tonic immobility PTSD Script-driven Posturography Heart rate Heart rate variability 1. Introduction Tonic immobility has been studied in animals for over three centuries (Maser and Gallup, 1977). It is elicited in a context of inescapable threat and is characterized by reversible, profound state of physical inactivity and relative unresponsiveness to external stimuli. Studies in rodents on the neural underpinnings of tonic immobility revealed an intricate set of connections involving several neurotransmitters and brain structures including the periaqueductal gray matter (Monassi and Menescal-De-Oliveira, 2004; Vieira et al., 2011), hypothalamus (Oliveira et al., 1997), amygdala (Leite-Panissi et al., 2003; Leite-Panissi et al., 2006), raphe nucleus (Ferreira and Menescal-De-Oliveira, 2009), and anterior cingulate (Coutinho and Menescal-De-Oliveira, 2010) in a neural network of great complexity. Tonic immobility is considered the last-ditch defense against entrapment by a predator within a sequence of defensive responses: freeze, flight, fight and tonic immobility (Ratner, 1967). The initial stage of freezing, also called “attentive immobility” (Marks, 1987), is a common adaptive defensive behavior when a potential threat is detected. Being motionless increases the chances to go unnoticed by a predator. If attack starts, overt defense (flight or fight) takes place. When life-threat escalates in the confrontation with a predator, tonic immobility occurs, reducing the probability of continued attack. Different from the attentive immobility (i.e. freezing), which occurs in the lowest threat stage of the defense cascade, tonic immobility is a last antipredator resort when survival is extremely threatened. Some researchers have studied human psychophysiology in the perspective of this defense cascade model (Bradley et al., 2001; Lang et al., 1997; Mobbs et al., 2009), but they focused on the freeze, flight, and fight reactions, overlooking tonic immobility. Traumatic events involving intense and inescapable life threats may have the power to evoke tonic immobility-like reactions in humans. Indeed, reports of immobility in life-threatening events from female victims (“rape paralysis”) may parallel tonic immobil- 6 2014-‐10-‐03 A= studera psykisk sjukdom i djur Kan man modellera psykisk sjukdom i djur? • Egentligen inte! • (Men kanske. Åtminstone bitar) Modeller för psykiatrisk sjukdom 7 2014-‐10-‐03 Varför inte? Exemplet depression • DiagnosSceras Sll stor del via paSent-‐ och anhörigintervjuer Diagnosis of Depression - DSM-IV-TR Criteria for Major Depressive Episode and Major Depressive Disorder Major depressive episode criterion: A. At least five of the following symptoms have been present during the same 2-week period and represent a change from previous functioning: at least one of the symptoms is either 1) depressed mood or 2) loss of interest or pleasure. 1. Depressed mood most of the day, nearly every day, as indicated either by subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful) 2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated either by subjective account or observation made by others) 3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day 4. Insomnia or hypersomnia nearly every day 5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) 6. Fatigue or loss of energy nearly every day 7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick) 8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others) 9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or specific plan for committing suicide B. The symptoms do not meet criteria for a mixed episode. C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The symptoms are not due to the direct physiological effects of a substance (e.g. a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism). E. The symptoms are not better accounted for by bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation. Major depressive disorder, single episode criterion: A. Presence of a single major depressive episode. B. The major depressive episode is not better accounted for by schizoaffective disorder and is not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. C. There has never been a manic episode, a mixed episode, or a hypomanic episode. Major depressive disorder, recurrent criterion: Modeller för psykiatrisk sjukdom A. Presence of two or more major depressive episodes (each separated by at least 2 months in which criteria are not met for a major depressive episode.) B. The major depressive episodes are not better accounted for by schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. C. There has never been a manic episode, a mixed episode, or a hypomanic episode. Adapted from: Practice Guideline for the Treatment of Patients With Major Depressive Disorder (MDD), Third Edition, American Psychiatric Association, 2010 Source: Reprinted from Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. © 2011 Alere. All rights reserved. DEP 0211 Varför inte? Exemplet depression • En del aspekter går (synbarligen) a= testa i djur; anhedoni, sömn-‐ och apStstörningar, psykomotorisk hämning • En del är (troligen) omöjliga; starka skuldkänslor, värdelöshetskänslor, dödslängtan, ledsenhet Modeller för psykiatrisk sjukdom 8 2014-‐10-‐03 Omöjliga? • Självupplevda och svårtolkade symptom – hur veta a= en rå=a är ledsen? (Hör röster? Har en störd kroppsuppfa=ning?) • De flesta djur verkar sakna en upplevelse av jaget, medvetenhet om döden och förmåga Sll existenSell reflekSon -‐ relaterade symptom är i sådana fall omöjliga a= modellera • Depression är en ’existensiell’ sjukdom! Modeller för psykiatrisk sjukdom De flesta djur? PLoS BIOLOGY Mirror-Induced Behavior in the Magpie • Hur testa (Pica sådant? anske bofara pica): K Evidence Self-Recognition problem med modellerna? Mirror self-recognition in the bottlenose dolphin: A case of cognitive convergence • Exemplet självmedvetenhet & spegeltestet Self-recognition in an Asian elephant • Ses hos människor eVer ≈18 månaders ålder • THos väldigt få andra djur Helmut Prior1*, Ariane Schwarz2, Onur Güntürkün2 1 Institut für Psychologie, Goethe-Universität, Frankfurt am Main, Germany, 2 Institut für Kognitive Neurowissenschaften, Biopsychologie, Ruhr-Universität Bochum, Bochum, Germany Comparative studies suggest that at least some bird species have evolved mental skills similar to those found in ‡¶ Diana Reiss*†‡§ and Lori Marino humans and apes. This is indicated by feats such as tool use, episodic-like memory, and the ability to use one’s own †Center for not experience predicting the behaviorSociety, of conspecifics. is, however, yet clearResearch whether *Osborn Laboratories of Marine Sciences, New York in Aquarium, Wildlife Conservation Brooklyn, NY It 11224; Environmental andthese skills are accompanied and In Behavioral Biology Program,behavior The Centerin forresponse Behavioral Neuroscience, Conservation, Columbia University, New NY 10027; and ¶Neuroscience byYork, an understanding of the self. apes, self-directed to a mirrorand has been taken as evidence of The Living Links Center for the Advanced Study of Ape and Human Evolution, Emory University, Atlanta, GA 30322 self-recognition. We investigated mirror-induced behavior in the magpie, a songbird species from the crow family. As testing behavioral contingencies. When provided with a mark, magpies showed spontaneous mark-directed behavior. Our findings provide the first evidence in Rockefeller apes, some individuals behaved in 20, front the mirror if they were Communicated by Donald R. Griffin, The University, New York, NY, February 2001 of (received for reviewas October 3, 2000) The ability to recognize oneself in a mirror is an exceedingly rare Phase 2 in a pool with nonreflective walls in which we affixed a of mirror self-recognition in a non-mammalian species. They suggest that essential components of human selfcapacity in the animal kingdom. To date, only humans great†, Frans mirror ade subset of ‡sessions (Fig.Reiss 1B). §¶! Joshua M. and Plotnik* B. in M.in Waal* ,vertebrate and Diana recognition have evolved independently different classes with a separate evolutionary history. apes have shown convincing evidence of mirror self-recognition. The first and primary subject of the study was a 13-year-old §Osborn Laboratories of Links, Yerkes National Primate Research Center, andmagpie Department of Psychology, University, Atlanta, GAe202. 30322; Two dolphins were exposed to reflective surfaces, and both demcaptive-born male bottlenose dolphin (Tursiops housed Citation: Prior H,*Living Schwarz A, Güntürkün O (2008) Mirror-induced behavior in the (Pica pica): Evidencetruncatus) of Emory self-recognition. PLoS Biol 6(8): doi:10.1371/journal. ¶Department of Ecology, Evolution, and Environmental Marine New to York Aquarium, Wildlife Conservation Society, Brooklyn, NY 11224; andbottlenose onstrated responses consistent pbio.0060202 with the use of Sciences, the mirror with the other subject, a 17-year-old captive-born male Biology, Columbia University, New York, NY 10027 investigate marked parts of the body. This ability to use a mirror dolphin at the New York Aquarium in Brooklyn, NY. In none of to inspect parts of the body is a striking example of evolutionary trials in which13, one animal was marked was there any discernable Contributed by Frans B. M. dethe Waal, September 2006 Within humans and apes, self-recognition might reflect a convergence with great apes and humans. Introduction reaction on the part of the companion dolphin to the mark. homologous trait, and whereas findings in other mammals hint at Considered an indicator of self-awareness, mirror self-recognition Furthermore, all instances of mark-directedlarge behaviorscomplex occurredbrain (19, 20), we introduced three adult (MSR) has long seemed limited to humans and both Asian (Elephas at the Bronx Zoo in aInconvergent evolution. Aelephants likely reason for maximus) such convergent Since the pioneering [1],companion a numberdolphin ofapes.was when the not nearfemale the same reflective he capacity for mirror self-recognition (MSR) has been work found by Gallup phylogeny and human ontogeny,of MSR is thought to correlate with ofNew Cityduring, to ainjumbo-size mirror (244 ! 244 cm) in a variant evolution self-recognition dolphins and elephants is the have investigated thenot occurrence mirror-induced surface as the subject. For 4 years before, and for York a period only in humans and great apesstudies (1–8). In humans, MSR does higher forms of empathy and altruistic behavior. Apart from of the classical mark test (1)understanding using both visual convergent evolution of complex social and and ‘‘sham’’ self-directed behavior in animals of a great range of species. the study, the two dolphins were housed for a part of each year in emerge reliably until 18–24 months of age (9) and marks the humans and apes, dolphins and elephants are also known for such marks (3). [10]. If self-recognition is linked to empathetic behavior Most animals exposed to a mirror respond with socialglass walls. a pool with three reflective Therefore, we did not expect beginning of a developmental process of achieving increasingly capacities. After the recent discovery of MSR in dolphins (Tursiops Elephants have the advantage that they can touch most of their highly social some birds species, in behavior, e.g., aggressive displays, our and continue to do so subjects to exhibit behaviors typical developed of animals who areunderstanding, initially abstract psychological levels of self-awareness, including introspectruncatus), elephants thus were the next logical candidate species. own body with their trunks, thus permitting an unequivocal mark exposed to(Elephas a mirror (31). The dolphins had prior trainingfamily, on tion and mental state attributionduring (10, 11). The firsttesting. evidence the corvid are likely candidatesMSR for in two Asian repeated Infor a few ape species, however, We exposed three Asian elephants maximus) toparticular a large from test. A previous failed attempt to demonstrate MSR in a nonhuman species wasbehavior experimentally demonstrated in their behaviors for Animals public demonstrations but no training toof studies from the past years self-recognition, too.inArelation number changes repeated presentations a mirror. mirror over to investigate responses.with that possess MSR elephants presented the animals with a relatively small mirror the common chimpanzee (1), but numerous subsequent attempts surfaces or onfor cognitive tasks. demonstrated elaborated understanding Social behavior decreases, and reflective the mirror is behavior used typically progress through four stages of whenhave facing a that was an kept at a distance, well out ofof social trunk-reach (21). showed no convincing evidence exploration of self-recognition in a variety of During an experiment, the dolphin was videotaped in the particularthat during competition It hassurface should of the(i)own body. This suggestive of(e.g.,relations, mirror: social responses, (ii) physicalevidence inspection looking inAssuming physical explorationfor of food. the mirror other primates and nonprimates, including monkeys, lesser apes, presence or mirrorsbeen for (iv) 30 minbebefore min process behind mirror), (iii) repetitive behavior, and part ofand the30 learning and thatcaches mirror size matters, shown that own experience in (5) pilfering self-recognition is the further corroborated bymirror-testing theabsence mirror of and and elephants (12–18). All of these species, including African graythemselves. after a Visible feeding context at the end of which the an animal was realization of seeing marks and invisible shamwe built almost 2.5-m-tall elephant-resistant mirror to allow facilitates predicting similar behavior in others [11], and that mark an individual is experimentally provided with a parrots (19) demonstrate the ability to test. use aIfmarks mirror to mediate or marked, sham-marked, or not touched at all. Both animals were appliedseen to the elephants’ heads to test they [12] close-up inspection of the reflectivewho surface (Fig. 1). Here we magpies and scrub jays [13] remember of their mark thatcontinues cannot were be directly but is, however, visible inwhether guide their behavior. A provocative debate to rage thentest’’ given theMSR standard signal releasing them from their stations. would pass the about litmus ‘‘mark for in which an individual demonstrate that allduring three subjects reached the aforementioned conspecifics observed them storing. Thus, foodthe mirror, increased exploration of the own body and selfwhether self-recognition in great apes implies that they areuses alsoa mirror Theto synchronized steppingimperceptible away of the trainers the pool’s spontaneously touch an otherwise third from and fourth stages of MSR progression and that one subject storingsignifying birds might particularly apt in empathy and directed actions(20). towards the markedge suggest thatnormal the mirror capable of more abstract levels of self-awareness was the release stimulus thatthe thebe feed was mark on itsTherefore, own body. Here, we report a successful MSR elephant passed mark test. perspective taking, which imagespecies is being perceived as striking self. Fairly clear of thisroutinely research on self-recognition in other will havereport profound over. Theinevidence dolphins were trained to go to and stayhave (or been suggested to coevolve study and parallels the progression of responses implications for the idea that humans are the only species to with mirror self-recognition [14]. has been obtained foramong chimpanzees [1], orang-utans [2], and Results Discussion station) at a elephants. particular location in the pool, andand during the to mirrors apes, dolphins, and These parallels conceive of their own identity. pygmy chimpanzees An self-recognition in corvids is not onlyThere of experiments, theymost werelikely stationed at investigation two locations for [3]. In gorillas and gibbons, some authors suggest convergent cognitive evolution related to separate Baseline,of Controls, and Initial Mirror Exposure. were five The apparent confinement of self-recognition great apes the marking, sham-marking, nonmarking procedures. A non- baseline regarding the convergent evolution of covered social intellireported failure ofsociality self-recognition [4,5] whereas others orinterest complexto and cooperation. experimental phases: (T1), mirror (T2), open Modeller för psykiatrisk sjukdom M PSYCHOLOGY and humans has stimulated scientific interest in thefindings evolutionary toxic marker Westborough, mirror (T3), covered-mirror sham (T4), and the mark test (T5). gence, it is(Entré, also valuable for an understanding of the general reported positive in at least onetemporary individualblack [6,7].ink It Entré significance of MSR based on common aspects the social MA) used to the dolphin on different parts ofcognitive its body cognitionof" mirror self-recognition "was theory of mind " intelligence " Happy, Maxine, and Patty all spent more time close to the principles that govern evolution and far their undershould be mentioned that even in the chimpanzee, themark species ecology, cognition, and neurobiology of these species (21–25). that were not visible to it without theneural use ofmirror a mirror (Fig. 2A). of open empathy during 3Mammals days covered mirrorthe (i.e., T3 vs. T2; lying mechanisms. and vs. birds inherited most studied and with the most convincing findings, clear-cut Dolphins have a high level of encephalization and behavioral and Marks were either cross-hatched and triangular or circular, and Happy, 19.4 vs. 0.2%; Maxine, 37.9 vs. 1.3%; and Patty, 49.7 vs. same brain components from their last common ancestor evidence of self-recognition is not obtained in all individuals cognitive complexity (26–29), but previous attempts to demonwere(MSR) !6.4 cm in diameterrare (Fig.in2B). Marks were placed on 3.3%), indicating that time spent at the mirror was due to its irroris self-recognition is adults exceedingly the300 nearly million years ago and have since then independtested. Prevalence about 75% in young and strate MSR in dolphins have been suggestive yet inconclusive reflective qualitiestorather than to the novelty of the apparatus. different body areas so that the subject would not habituate animal kingdom (1). Attempts to MSR outently developed a relatively large forebrain pallium. However, considerably less in young and individuals [8].demonstrate Findings because of difficulties in implementing adequate controls nec-aging T3, three subjects showed investigative behavior of the the marking location and to enable to testDuring whether thealldolphin side of the Hominoidea (i.e., humans and apes) have thususfar both classes differ to the internaland probable otherits than apes essary to obtain robust evidencesuggestive of MSR inofanself-recognition animal unable toin mammals surface frameregard including touching would orient body differentially to themirror mirror substantially to view and the with failed (2), with the notable exception of one report on dolphins display self-recognition by touching a marked part of the body organization of their pallium, with a laminated have been reported for dolphins [9] and elephants [10]. In sessions, the protocol sniffing.was Foridentical Maxine andbirds Patty,lacking trunk-over-wall exploration (i.e., areas. sham-mark (Tursiops truncatus) (3).marked Animals that In demonstrate MSR typiwith a hand (30, 31). cortex but the having an organization of clustered monkeys, nonprimate mammals, and in (i) ainnumber of bird swinging of the trunk over and behind the wall on which the to that the actual mark(ii) sessions except that a developed water-filled cally go through four stages: social response, physical Conclusive evidence of self-recognition in a speciesofasthe phylomirror species, exploration and social displays were for marker was used to mirror), control possibility thatwas themounted) animal’s declined from the first through the fourth mirror inspectionmirror (e.g., looking behind the (iii)the repetgenetically distant from primates as dolphins would day of mirror exposure (Maxine, 10 to 0 times; Patty, 13 to 4 behavior attributable the tactile sensation of marking observed, but hintsplay at amirror-induced itive no mirror-testing behavior (i.e., was theself-directed beginning oftomirror un-Editor: Academic Frans de Waal, Emory University, United States of America pivotal role in determining whether this capacity is a byproduct never put her trunk over the mirror wall. Maxine rather theamark itself. The real of marktimes). and theHappy sham-mark behavior have been obtained [5]. self-directed Does thisthan mean cognitive derstanding), and (iv) behavior (i.e., recognition of factors specific to great apes and humans or whether more and Patty also attempted to physically Received April 7, 2008; Accepted July 11, 2008; Published August climb 19, 2008the mirror wall to were applied to the dolphin’s skin in if asaclose to the same manner the apes mirror image as self) (3,species 4). Thewith final stage is verified Rubicon with and a few other complex general characteristics, such as a high level of encephalization, look over and it (see Movie 1, which is published as possible (e.g., duration of marking, amount pressure toisbehind skin, subject test’’ by spontaneously using the mirror Copyright: ! 2008of Prior et al. This an open-access article distributed under the socialofbehavior onpasses one the side‘‘mark and as the rest of the animal could help to explain the evolution this capacity. supporting information on the PNAS web site), and both, on termsmark, of the sham-mark, Creative Commons Attribution which permits unrestricted andimply type that of mark mark). and non- License, touch anside? otherwise imperceptible onPostfeeding its own body (1). kingdom ontothe other This might animal selfseparate occasions, try tothe getoriginal their trunks use, for distribution, and in any medium, to provided author underneath sessions were 30 min in reproduction the presence orseemed themammals markmarked is recommended onlyvideotaped if the preceding General Methods and Procedures recognitionApplication is restrictedofto with large brains and and source are credited. 9 2014-‐10-‐03 ESska aspekter • E= djur som fakSskt kan uppfylla alla DSM 5-‐ kriterier för depression skulle i allt väsentligt ha vad vi betraktar som e= mänskligt känsloliv – vilket inte ens mänskliga spädbarn har! • ESskt försvarbart a= använda som försöksdjur? Modeller för psykiatrisk sjukdom Hur gör man då? • Behöver vi modellera ex. depression perfekt? Kanske inte! • Endofenotyper Modeller för psykiatrisk sjukdom 10 2014-‐10-‐03 Personlighet • Personlighet – stabila interindividuella skillnader i beteende • Även djur har personlighet; ’ängslighet’/ undandragande beteende, impulsivitet, etc. • Samma skäl som i människor; fitnessfördelar för olika strategier beroende på omgivningen och omgivningen är ombytlig! • Gäller i princip hela djurserien; troligen homologa system åtminstone i däggdjur Modeller för psykiatrisk sjukdom Personlighet Modeller för psykiatrisk sjukdom 11 2014-‐10-‐03 Stark associaSon mellan psykiska sjukdomar och personlighetsdrag • Även om själva sjukdomarna kan vara specifika för människan kan deras associaSon med personlighet/temperament innebära a= vissa grundläggande mekanismer för exempelvis ångest/extrem ängslighet kan ulorskas i djur Modeller för psykiatrisk sjukdom Stark associaSon mellan psykiska sjukdomar och personlighetsdrag Psychiatry Research 169 (2009) 159–163 SCHIZOPHRENIA RESEARCH Contents lists available at ScienceDirect Psychiatry Research Schizophrenia Research 12 (1994) 81-88 j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p s yc h r e s Personality variations in healthy relatives of schizophrenics Wolfgang Maier *, Jtirgen Minges, Dirk Lichtermann, Reinhard Heun, Petra Franke Personality trait predictors of bipolar disorder symptoms Department of Psychiatry, University of Maim, Untere Zahlbacher Str. 8, D-55131 Mainz, Germany (Received 26 January 1993; revision received 20 May 1993; accepted 2 1 May 1993 Lena Catherine Quilty a,b, Martin Sellbom c, Jennifer Lee Tackett d, Robert Michael Bagby a,b,⁎ a Clinical Research Department, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada c Department of Psychology, Kent State University, Kent, OH, USA d Department of Psychology, University of Toronto, Toronto, ON, Canada b Abstract A familial relationship between schizophrenia and schizotypal personality disorder is widely acknowledged; the familial relationship between schizophrenia and the broad continuum of schizoid personality variation is less clear. In a comprehensive relatives of a schizophrenics compared by self rated personality features a r t i cfamily l e study i n f healthy o b s t r a c were t with relatives of unipolar depressed patients and with relatives of controls. The dimension of schizoidia was not able Article The of purpose of the current was to examinescored the personality to distinguish thehistory: groups of relatives. However, relatives schizophrenics (in investigation particular male relatives) higher predictors of bipolar disorder Received 29 February 2008 symptoms, (bipolarity) or two-dimensional (mania and depression). A on ‘normalized’ personality dimensions such as ‘rigidity’ andconceptualized ‘neuroticism’.as one-dimensional Healthy relatives of probands with unipolar Received in revised form 3 July 2008 depression Accepted 12 revealed July 2008 a similar deviant Key words; Keywords: Personality 1. pattern. psychiatric sample (N = 370; 45% women; mean age 39.50 years) completed the Revised NEO Personality Inventory and the Minnesota Multiphasic Personality Inventory —2. A model in which bipolar symptoms were represented as a single dimension provided a good fit to the data. This dimension was predicted by assessment; Schizoidia; Neuroticism; Introversion; Rigidity; Family study Neuroticism and (negative) Agreeableness. A model in which bipolar symptoms were represented as two Depression Mania Personality Trait Introduction Five Factor Model MMPI-2 separate dimensions of mania and depression also provided a good fit to the data. Depression was associated with Neuroticism and (negative) Extraversion, whereas mania was associated with Neuroticism, Extraversion and (negative) Agreeableness. bipolar disorder can be usefully understood in terms of two anhedonia as a Symptoms relevant ofdiagnostic criterion for dimensions of mania and depression, which have distinct personality correlates. SPD. Empirical research provides strong evidence © 2008 Elsevier Ireland Ltd. All rights reserved. Modeller för psykiatrisk sjukdom Since the turn of this century it has been that schizophrenia and SPD are related by suggested that relatives of schizophrenics although common familial and genetic factors (Kendler not presenting with a psychotic disorder are at et al., 1985). The familial relationship of schizoelevated risk for schizophrenia-like personality phrenia to paranoid schizoid personality (Joffe et al., 1999; Cuellar et al., disordersand are largely indistinguishable 1. Introduction features (Rtidin, 1916). Most influential in this disorder has also beenThus, proposed although the 2005). while patients may experience lifetime episodes of both respect were Mania the writings by Kretschmer (1922) empirical support mania is not (Baron al., disorder diagnosis to codify andconvincing depression, the use of aetbipolar and depression have long been recognized as clinically relevant syndromes Mondimore, 2005); of both et this on schizoidia followed by (see Kallman ( 1938), and the inclusion 1984; Tsuang al., affective 1992). disturbance may be misleading. Anthe alternative current differentiation between bipolar and classes of affective in one diagnostic entity, however, is a by Rado (1953) and Meehldisturbance (1962) on schizotaxia More specifically classicalto the hypothesis by unipolar conceptualization of mania and depression as nosologicalClaridge proposition(1987) (American Psychiatric Asso-(1922) and the relatively so-called recent schizotype. Kretschmer and disorders Kallman is (the 1938) proposed separate but related disorders. Schweitzer et al. (2005) suggest that ciation, 1980). Criticisms of the union of mania and depression in a identified anhedonia, perceptual aberration and an excess of unsociable, indifferent, shy, hypersenepisodes of elevated mood be identified as “manic disorder,” and episingle diagnostic entity, and the identification of this entity as “bipolar” antisocial intendencies the crucial of cite that sitive and asthenicsodes behavior and of and of depression as aeccentric common comorbidity. Genetic data support nature, have as accumulated. First, features investigators the presence these concepts. on the feature Danishof bipolar adoption autisticthan preoccupations in familythatmembers of depression schizthe contention mania and are separable, but highly of maniaBased is the defining disorder, rather the ophrenics. with syndromes Kallman (McGuffin (1938) et this study (Kety, 1985) a mania new and diagnostic category, correlated al., 2003). Mania and depression presence of both depression. Moreover, not all patients withStarting further have by distinct coursesofof studies illness, associated features, treatment disorderdisorder experience(SPD), depressive et al., 2002), hypothesis was confirmed a series schizotypal bipolar personality was episodes intro- (Yazici and prognoses (Joffe et al., 1999; Cuellar et al., 2005). The with estimates of greater than 20%‘borderline’ of non-treatment-seeking bipolar duced in DSM-III in order to identify (including one implications study derived from the present of maniarates and of depression individuals “unipolar spectrum mania” (Kesslersample) et al., 1997). cases belonging to experiencing the schizophrenic comparingcomorbidity the prevalence schizo- might be conceptualized as related to both common and unique factors, a conceptual approach also the inclusion of mania and depression in a unitary illness (Spitzer et Second, al., 1979); in contrast to the aforemenphrenia-like personality disorders between families applied to comorbid conditions such as anxiety and depression. As implies that they reflect dysregulation along a single affective tioned concepts this category did not acknowledge of schizophrenics and controls. Kretschmer proexemplified by the work of Watson (2005), dimensional personality dimension (Cuellar et al., 2005); yet, empirical evidence for the posed amania more comprehensive hypothesis: (a) an of the common and specific traits can contribute to the delineation existence of mixed episodes and the inaccuracy of describing * Corresponding author. excess of a maladaptive personality disorder (which elements of psychopathology in such an approach, and may provide and depression as opposite syndromes challenges such an assumption (Bauer et al., 1994; Power, 2005). Third, the distinction between 0920-9964/94/$7.00 1994 Elseviermood Science B.V. All intimates rights reserved bipolar0and unipolar disorders that a disparity exists SSDI 0920-9964(94)E0051-T between the depressive episodes experienced in these two disorders; nosologically useful information in this regard. 1.1. Personality, mania and depression however, the depressive episodes experienced by patients with these The Five Factor Model (FFM) of personality is currently the most 12 2014-‐10-‐03 Begreppet endofenotyp • Vissa specifika drag/reakSoner kan vara mycket konserverade, såsom exempelvis olika skrämselreakSoner • Om associerade med sjukdom i människan – möjlig sak a= studera i djur Modeller för psykiatrisk sjukdom Modeller för psykiska och neuropsykiatriska Allstånd 13 2014-‐10-‐03 Modeller för ångestsjukdomar • • • • • Panikångest Generaliserat ångestsyndrom Social fobi Specifika fobier Pos=raumaSskt stressyndrom Modeller för psykiatrisk sjukdom: ångestsjukdomar Modeller för ångestsjukdomar • System för undvikande/ängsligt beteende/ rädsla verkar vara homologa i däggdjur, i viss mån för alla ryggradsdjur • Många modeller finns • Stammar avlade för ökad ’ängslighet’ Modeller för psykiatrisk sjukdom: ångestsjukdomar 14 2014-‐10-‐03 Elevated plus-‐maze • Gnagare är rädda för öppna ytor, starkt ljus och höjder • Dock nyfikna! • Generellt: akut SSRI minskar Sd i öppen arm, kroniskt SSRI, bensodiazepiner ökar den Modeller för psykiatrisk sjukdom: ångestsjukdomar Open field • LokomoSon och undvikande beteende • SSRI-‐ och bensodiazepineffekt, mindre tydligt än EPM dock Modeller för psykiatrisk sjukdom: ångestsjukdomar 15 2014-‐10-‐03 Startle • Djuret utsä=s för en hög ton och spri=er reflexivt Sll • Liknande tester i människa • Kan kopplas Sll e= negaSvt sSmulus (svag ström, exempelvis); förstärker effekten • ’Freezing’; liknande test där hur länge djuret stelnar Sll mäts Modeller för psykiatrisk sjukdom: ångestsjukdomar Modeller för depressionssjukdomar • Mycket komplex sjukdom • Stora delar går troligen inte a= modellera i djur • Tester för beteenden som i människa kan vara störda vid depression används Modeller för psykiatrisk sjukdom: ångestsjukdomar 16 2014-‐10-‐03 Forced swim test • Forced-‐swim test • Orörlighet i en stressande situaSon tas som intäkt för ’hjälplöshet’ • Svarar ’anSdepressivt’ på kroniskt SSRI men även på akut Modeller för psykiatrisk sjukdom: depressionssjukdomar Andra tester • Andra tester – Vogels konflik=est, preferens för sukros, sociala interakSonstester, olika kondiSoneringstester (biased a=enSon, bla.) • Stammar – Flinders sensiSve line, Wistar-‐Kyoto • Knockoutmodeller – TPH2, SERT, VMAT2 • Lesionsmodeller – bulbektomi Modeller för psykiatrisk sjukdom: depressionssjukdomar 17 2014-‐10-‐03 Modeller för psykossjukdomar • Svårt! Vad skall man testa? Hur vet man om en rå=a har störd verklighetsuppfa=ning? • Droger som inducerar psykos (som senare svarar på neurolepSka) används • Olika knock-‐outmodeller (dysbindin, neuregulin, m.m.) Modeller för psykiatrisk sjukdom: psykossjukdomar Modeller för psykossjukdomar • Tester: sociala tester, prepulsinhibiSon, kogniSva tester Modeller för psykiatrisk sjukdom: psykossjukdomar 18 2014-‐10-‐03 Modeller för auSsm • Mycket heterogen sjukdom, inga farmakologiska behandlingar mot kärnsymptomen • Finns monogena sjukdomar med auSsmbild (fragil X, tuberös skleros, m.m.) -‐ knockoutmodeller • Sociala tester; social preferens Modeller för psykiatrisk sjukdom: AuAsm Andra modeller • Aggression – resident intruder • Utny=jar a= gnagare hävdar revir • SSRI sänker aggression akut & kroniskt Modeller för psykiatrisk sjukdom: Andra modeller 19 2014-‐10-‐03 Kort om neurologiska Sllstånd • Mer likt ’annan’ forskning; fysiologiska principer oVare överförbara mer eller mindre direkt • OVare idenSfierad sjukdomsprocess (celldöd i subst. nigra, CAG-‐repeats i hunSngSngenen) Experimentdesign Forskningsexempel 20 2014-‐10-‐03 Outline • QuesSons: do rats separated with respect to baseline anxiety-‐like behaviour differ in their response to acute serotonin elevaSon (as is the case in humans)? • Do differences in baseline anxiety-‐like behaviour reflect differences in serotonergic neurotransmission? Manuscript II Outline • Study I: 48 Wistar males were assayed in the EPM. Three weeks later, paroxeSne or saline was administered and the animals tested in the EPM as well as in the OF • Study II: 30 Wistar males were assayed in the EPM. Three weeks later, the animals were sacrificed and their brains removed for mRNA extracSon and RT-‐qPCR. Manuscript II 21 2014-‐10-‐03 Results • In study I, ’anxious’ rats exhibited a stronger ’anxiogenic’ response to an acute SSRI in the EPM as well as in the OF, the la=er effect completely absent in the other animals Manuscript II Results • In study II, ’anxious’ rats had a higher expression of a number of genes important for serotonergic neurotransmission Manuscript II 22 2014-‐10-‐03 Conclusions • Similar to the situaSon in humans, rats exhibiSng higher basal anxiety-‐like behaviour respond more strongly to acute serotonin elevaSon • Animals exhibiSng higher anxiety-‐like behaviour have higher expression of genes associated with serotonergic neurons and serotonin synthesis in the raphe nuclei • Our results support the noSon of serotonin exerSng, at least partly, an anxiogenic influence Manuscript II Tack! Och trevlig helg! 23