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

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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

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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

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10

0

-10

-20 Rsq = 0.1118

r = -0.33, p=0.002

Effect of Unusual Perceptual Experiences

Unusual Perceptual Experiences

6420-2-4

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sid

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ha

se

1 a

cc

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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

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an

Nu

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Co

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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.