Dopaminergic Genes, Schizotypal Personality and Schizophrenia: Effects on Category Learning

1
Dopaminergic Genes,Schizotypal Personality and
Schizophrenia Effects on Category Learning
Dopaminergic Genes,

• Mary Cochrane Alan Pickering
• Department of Psychology
• a.pickering_at_gold.ac.uk

2
Acknowledgements

• Recruiting and rating patients-
• Ian Petch, St Georges and South West London
  Hospital Trust
• Genotyping-
• Dr John Powell, Institute of Psychiatry, London

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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

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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

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Schizotypal Personality Multidimensionality
Schizotypal personality has 3 or 4 correlated
factors

• Positive schizotypy
• Disorganised schizotypy
• Negative schizotypy
• 4th factor Impulsive nonconformity
• Is this really schizotypal personality?

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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

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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

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Schizotypal Personality Measures

• Positive Schizotypy
• OLIFE Unusual experiences (UnEx)
• SPQ Cognitive-perceptual factor

• Negative Schizotypy
• OLIFE Introvertive anhedonia (IntAnh) SPQ
  negative factor

• Disorganised Schizotypy
• OLIFE Cognitive Disorganisation (CogDis) SPQ
  Disorganisation

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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
• dont belong to you?
• -Sometimes my thoughts are as real as
• actual events in my life

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The CL Task

• Based on Maddox Filoteo (2001)
• The stimuli were composed of a vertical and a
  horizontal lines

Category 2
Category 1
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The CL Task contd

• 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
  Parkinsons disease patients (Maddox Filoteo,
  2001)
• Horizontal and vertical lengths sampled randomly
  from independent normal distributions

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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
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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
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CL Task Final Details

• Trial present stimulus mouse-click response
  text tone feedback
• Two phases, 50 (40) trials per phase
• Two optimal rules
• if vgth then cat1 if hgtv then cat2
• if hgtv then cat1 if vgth then cat2
• Optimal rule in phase 2 reversed c.f. phase 1
  without warning
• Stimulus sets and rules counterbalanced over
  phases

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Study 1 Schizotypal Personality

• N84 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)

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Study 1 GLM Analysisof CL (number correct)

• Within-subjects
• PHASE (first, second)
• Between-subjects
• Drugs, set order
• Covariates
• Working memory accuracy
• Matrices IQ
• SPQ 3 factors (pos, neg, disorg)

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Study 1 Results for non-personality variables

• Main effects
• Working memory (plt0.01)
• Matrices IQ (plt0.005)
• Illicit drug use (plt0.005)
• Interactions with PHASE
• None significant

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Study 1 Results for personality variables

• Main effects
• Positive schizotypy ns
• Negative schizotypy ns
• Disorganised schizotypy ns
• Interactions with PHASE
• Positive schizotypy (plt0.05)
• Negative schizotypy ns
• Disorganised schizotypy ns

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Effect of Positive Schizotypal Personality
Effects of drug use, IQ, and WM removed from CL
Accuracy
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Effect of Positive Schizotypal Personality
r -0.28, p0.011
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Effect of Odd Beliefs and Magical Thinking (OBMT)
r -0.33, p0.002
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Effect of Unusual Perceptual Experiences
Partial r 0.20, plt0.07 (OBMT partialled)
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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

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Study 2 Schizophrenia (SZ)

• Tested patients and age-matched healthy controls
  on same task (40 trials per phase)
• Patients symptoms rated using Andreasens
  SAPS/SANS schedule
• Patients and controls both given OLIFE
  schizotypal personality questionnaire

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Study 2 Sample Details
plt0.05 plt0.01
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Study 2 Patient Details
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Study 2 Personality
plt0.05 plt0.01
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Study 2 1st GLM Analysisof CL (no. correct)

• Within-subjects
• PHASE (first, second)
• Between-subjects
• Group (SZ vs control), set order

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Study 2 Results 1
plt0.05
plt0.05

• Main effect of group, plt0.005

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Study 2 2nd GLM Analyses

• Within-subjects
• PHASE (first, second)
• Between-subjects
• Group (SZ vs control)
• Covariates (each separately)
• Matrices IQ
• WM accuracy
• Smoking (as factor)

Validity?
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Study 2 Results 2

• Including IQ
• IQ plt0.05 Group plt0.05
• Including WM Accuracy
• WM plt0.08 Group plt0.05
• Including Smoking
• Smoking pgt0.8 Group p0.01
• GroupSmoking pgt0.4

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Correlations with symptoms
N20 all ns pgt0.15
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Correlations with OLIFE in SZ
N20 all ns pgt0.1 except plt0.05 p0.06
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Correlations with OLIFE in Controls
N18 all ns pgt0.4
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Study 2 3rd GLM Analyses

• Within-subjects
• PHASE (first, second)
• Between-subjects
• Group (SZ vs control)
• Covariate
• OLIFE-UnEx

Validity?
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Study 2 Results 3

• Including OLIFEUnEx
• UnEx plt0.05 Group plt0.001
• No sig effects involving PHASE
• For phase 1 performance only
• UnEx plt0.02 Group plt0.005
• For phase 2 performance only
• UnEx pgt0.5 Group plt0.02

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Effect of OLIFE Unusual Experiences
Effect of group removed from CL accuracy r
0.36, plt0.03
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Effect of OLIFE Unusual Experiences
Effect of group removed from CL accuracy r
0.08, pgt0.5
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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

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Relevant References

• Maddox 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.