dopaminergic genes, schizotypal personality and schizophrenia: effects on category learning mary...
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Dopaminergic Genes,Schizotypal Personality and Schizophrenia: Effects on
Category Learning
Mary Cochrane & Alan PickeringDepartment of Psychology
a.pickering@gold.ac.uk
Dopaminergic Genes,
Acknowledgements
Recruiting and rating patients:-Ian Petch, St George’s and South West London Hospital Trust
Genotyping:-Dr John Powell, Institute of Psychiatry, London
Overview• Take a single category learning (CL)
task• In 3 studies, look at the influence of 3
variables related to schizophrenia-schizotypal personality traits-schizophrenia (SZ) itself-4 DA genotypes implicated in SZ
What Are Schizotypal Personality Traits?
• Stable traits in healthy individuals• Tendencies to show features of
behaviour/cognition that are qualitatively similar to those of schizophrenic patients
• Underlying continuum model
Schizotypal Personality: Multidimensionality
Positive schizotypyDisorganised schizotypyNegative schizotypy
4th factor = Impulsive nonconformity:Is this really schizotypal personality?
Schizotypal personality has 3 or 4 correlated factors …
Why Study Schizotypal Personality Traits?
• Testbed for schizophrenia in readily-available, healthy individuals
• Performance of high scorers should be similar to schizophrenics
• Behaviour not contaminated by medication, illness, hospitalisation etc
More Reasons to Study Schizotypal Personality Traits
• May find specific associations with one schizotypal factor
• Generates predictions for associations with specific SZ symptoms
• Our previous work found positive schizotypal personality was negatively associated with rule-based category learning (RB CL), esp. after a rule-shift
Schizotypal Personality Measures• Positive Schizotypy
OLIFE: Unusual experiences (UnEx);SPQ: Cognitive-perceptual factor
• Negative SchizotypyOLIFE: Introvertive anhedonia (IntAnh); SPQ negative factor
• Disorganised SchizotypyOLIFE: Cognitive Disorganisation (CogDis); SPQ Disorganisation
Example OLIFE Items
• Positive Schizotypy: Measure = Unusual Experiences (30 items)-I have felt that I have special, almost
magical powers-Do you ever feel that your thoughts
don’t belong to you?-Sometimes my thoughts are as real as actual events in my life
The CL Task• Based on Maddox & Filoteo (2001)• The stimuli were composed of a vertical
and a horizontal lines
Category 1 Category 2
The CL Task cont’d• Solvable to 90% accuracy by using a
simple verbal rule:if horizontal line is longer than vertical, then is in category 1 (2)
• Accuracy correlated –0.99 with WCST errors in Parkinson’s disease patients (Maddox & Filoteo, 2001)
• Horizontal and vertical lengths sampled randomly from independent normal distributions
CL Task Stimuli: Set 1
H len= 115 (cat 1) 185 (cat 2); s.d.= 30 (both)
V len= 185 (cat 1) 115 (cat 2); s.d.= 30 (both)
Optimal accuracy = 92%
Horizontal line length (pixels)
3002001000
Ve
rtic
al
lin
e l
en
gth
(p
ixe
ls) 300
200
100
0
Category
2
1
CL Task Stimuli: Set 2
H len= 115 (cat 1) 185 (cat 2); s.d.= 30 (both)
V len= 185 (cat 1) 115 (cat 2); s.d.= 30 (both)
Optimal accuracy = 84%
Horizontal line length (pixels)
3002001000
Ve
rtic
al
lin
e l
en
gth
(p
ixe
ls) 300
200
100
0
Category
2.00
1.00
CL Task: Final Details• Trial= present stimulus; mouse-click
response; text + tone feedback• Two phases, 50 (40) trials per phase• Two optimal rulesa) if v>h then cat=1; if h>v then cat=2b) if h>v then cat=1; if v>h then cat=2• Optimal rule in phase 2 reversed c.f.
phase 1 without warning• Stimulus sets and rules
counterbalanced over phases
Study 1: Schizotypal Personality
• N=84 healthy young subjects, some students
• Mean age= 23.5 (18-37)• 27% males• SPQ used to measure schizotypal
personality• Also measured IQ, working memory
and illicit drug use (yes/no)
Study 1: GLM Analysisof CL (number correct)
• Within-subjectsPHASE (first, second)
• Between-subjectsDrugs, set order
• Covariates Working memory accuracyMatrices IQSPQ: 3 factors (pos, neg, disorg)
Study 1: Results for non-personality variables
Main effectsWorking memory (p<0.01)Matrices IQ (p<0.005)Illicit drug use (p<0.005)Interactions with PHASENone significant
Study 1: Results for personality variables
Main effectsPositive schizotypy nsNegative schizotypy nsDisorganised schizotypy ns
Interactions with PHASEPositive schizotypy (p<0.05)Negative schizotypy nsDisorganised schizotypy ns
Effect of Positive Schizotypal Personality
PHASE
21
Re
sid
ua
l C
L P
erf
orm
an
ce 2
1
1
0
-1
-1
-2
SPQ-Pos group
low
high
Effects of drug use, IQ, and WM removed from CL Accuracy
Effect of Positive Schizotypal Personality
SPQ Positive Schizotypy
3020100-10
Re
sid
ua
l p
ha
se
2 a
cc
ura
cy
20
10
0
-10
-20 Rsq = 0.0790
r = -0.28, p=0.011
Effect of Odd Beliefs and Magical Thinking (OBMT)
SPQ Odd Beliefs & Magical Thinking
86420-2
Re
sid
ua
l p
ha
se
2 a
cc
ura
cy 20
10
0
-10
-20 Rsq = 0.1118
r = -0.33, p=0.002
Effect of Unusual Perceptual Experiences
Unusual Perceptual Experiences
6420-2-4
Re
sid
ua
l p
ha
se
1 a
cc
ura
cy
10
0
-10
-20 Rsq = 0.0418
Partial r = +0.20, p<0.07 (OBMT partialled)
Study 1: Conclusions• Positive schizotypy impairs RB CL, esp.
after rule shift • Effect after a rule shift appears
primarily mediated by “delusional” aspects of positive schizotypy
• RB CL may be facilitated by “hallucinatory” aspects of positive schizotypy
• These effects are after removing effects of WM, IQ and use of drugs
Study 2: Schizophrenia (SZ)
• Tested patients and age-matched healthy controls on same task (40 trials per phase)
• Patients’ symptoms rated using Andreasen’s SAPS/SANS schedule
• Patients and controls both given OLIFE schizotypal personality questionnaire
Study 2: Sample DetailsVariable SZ
(N=20)Controls(N=18)
AGE 34.3 32.8
M:F 18:2 16:2
English=1st lang 16 16
Smoker:Non-S 15:5 7:11*
Matrices (scaled score)
10.9 13.3**
WM (% correct) 73.1 91.3**
*p<0.05; **p<0.01
Study 2: Patient DetailsDuration of illness 10.6 yrs
In- vs. out-patients 10 vs. 10
Medicated 20/20
SAPS Positive 5.05
SANS Negative 9.05
SANS Disorganised 1.9
SANS Attentional Imp. 2.8
Global Hallucinations 2.2
Global Delusions 2.9
Study 2: Personality
OLIFE Score SZ (N=20)
Controls(N=18)
Positive (UnEx) 14.9 8.2**
Negative (IntAnh) 10.6 5.9**
Disorg. (CogDis) 16.0 10.2*
Other (ImpNon) 8.2 9.5
*p<0.05; **p<0.01
Study 2: 1st GLM Analysisof CL (no. correct)
• Within-subjectsPHASE (first, second)
• Between-subjectsGroup (SZ vs control), set order
Study 2: Results 1
Main effect of group, p<0.005
PHASE
21
Me
an
Nu
mb
er
Co
rre
ct
32
31
30
29
28
27
26
25
24
SZ
Cont
p<0.05
p<0.05
Study 2: 2nd GLM Analyses
• Within-subjectsPHASE (first, second)
• Between-subjectsGroup (SZ vs control)
• Covariates (each separately)Matrices IQWM accuracySmoking (as factor)
Validity?
Study 2: Results 2Including IQIQ p<0.05; Group p<0.05Including WM AccuracyWM p<0.08; Group p<0.05Including SmokingSmoking p>0.8; Group p=0.01Group*Smoking p>0.4
Correlations with symptoms
Ph1 Ph2 Ph1+Ph2
Ph1-Ph2
SAPS Positive 0.32 0.02 0.23 0.27
SANS Negative 0.01 -0.19 -0.11 0.16
SANS Disorganised 0.16 0.21 0.23 -0.03
SANS Attentional Imp. -0.05 -0.30 -0.21 0.19
Global Hallucinations 0.27 0.00 0.18 0.23
Global Delusions 0.28 0.04 0.21 0.21
N=20; all ns p>0.15
Correlations with OLIFE in SZ
Ph1 Ph2 Ph1+Ph2
Ph1-Ph2
OLIFE Positive (UnEX) 0.51* 0.14 0.43† 0.34
OLIFE Neg. (IntAnh) -0.31 -0.11 -0.27 -0.19
OLIFE Disorg. (CogDis) 0.31 0.06 0.24 0.22
OLIFE Other (ImpNon) 0.50* 0.08 0.38 0.37
N=20; all ns p>0.1; except *p<0.05; †p=0.06
Correlations with OLIFE in Controls
Ph1 Ph2 Ph1+Ph2
Ph1-Ph2
OLIFE Positive (UnEX) 0.20 -0.05 0.17 0.17
OLIFE Neg. (IntAnh) -0.04 0.27 0.14 -0.16
OLIFE Disorg. (CogDis) -0.05 -0.07 -0.09 -0.00
OLIFE Other (ImpNon) -0.11 0.13 -0.02 -0.15
N=18; all ns p>0.4
Study 2: 3rd GLM Analyses
• Within-subjectsPHASE (first, second)
• Between-subjectsGroup (SZ vs control)
• CovariateOLIFE-UnEx Validity?
Study 2: Results 3Including OLIFE:UnExUnEx p<0.05; Group p<0.001No sig effects involving PHASEFor phase 1 performance onlyUnEx p<0.02; Group p<0.005For phase 2 performance onlyUnEx p>0.5; Group p<0.02
Effect of OLIFE Unusual Experiences
Effect of group removed from CL accuracy; r = +0.36, p<0.03
OLIFE UnEX
3020100
Ph
ase
1 A
cc
ura
cy (
resid
)
20
10
0
-10
-20
Cont
SZ
Rsq = 0.1264
Effect of OLIFE Unusual Experiences
Effect of group removed from CL accuracy; r = +0.08, p>0.5
OLIFE UnEx
3020100
Ph
ase
2 A
cc
ura
cy (
resid
) 20
10
0
-10
-20
Cont
SZ
Rsq = 0.0062
Study 2: Conclusions• Schizophrenics are impaired at RB CL
relative to age-matched controls• Schizotypal personality scores are
higher in SZ than controls• No sig. negative effects of schizotypal
personality on RB CL were found• The study 1 trend for unusual
perceptual experiences to faciliatate RB CL was replicated
• This effect was indep. of group
Relevant ReferencesMaddox WT & Filoteo JV (2001). Striatal contributions to category
learning. J Int. Neuropsych. Soc., 7, 710-727.
Pickering, A.D. (2004). The neuropsychology of impulsive antisocial sensation seeking: From dopamine to hippocampal function? In: RM Stelmack (Ed.), On the psychobiology of personality: Essays in honor of Marvin Zuckerman (pp. 455-478). Elsevier.
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