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 paulc@lpc.grc.nia.nih.gov.
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