1. Dopaminergic Genes, Schizotypal Personality and Schizophrenia: Effects on Category Learning Mary Cochrane & Alan Pickering Department of Psychology a.pickering@gold.ac.uk Dopaminergic Genes,

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

3. 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

4. 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

5. Schizotypal Personality: Multidimensionality Positive schizotypy Disorganised schizotypy Negative schizotypy 4 th factor = Impulsive nonconformity: Is this really schizotypal personality? Schizotypal personality has 3 or 4 correlated factors …

6. 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

7. 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

8. 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

9. 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

10. The CL Task Based on Maddox & Filoteo (2001) The stimuli were composed of a vertical and a horizontal lines Category 1 Category 2

11. 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

12. 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%

13. 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%

14. CL Task: Final Details Trial= present stimulus; mouse-click response; text + tone feedback Two phases, 50 (40) trials per phase Two optimal rules a)if v>h then cat=1; if h>v then cat=2 b)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

15. 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)

16. Study 1: GLM Analysis of 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)

17. Study 1: Results for non- personality variables Main effects Working memory (p<0.01) Matrices IQ (p<0.005) Illicit drug use (p<0.005) Interactions with PHASE None significant

18. Study 1: Results for personality variables Main effects Positive schizotypy ns Negative schizotypy ns Disorganised schizotypy ns Interactions with PHASE Positive schizotypy (p<0.05) Negative schizotypy ns Disorganised schizotypy ns

19. Effect of Positive Schizotypal Personality Effects of drug use, IQ, and WM removed from CL Accuracy

20. Effect of Positive Schizotypal Personality r = -0.28, p=0.011

21. Effect of Odd Beliefs and Magical Thinking (OBMT) r = -0.33, p=0.002

22. Effect of Unusual Perceptual Experiences Partial r = +0.20, p<0.07 (OBMT partialled)

23. 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

24. 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

25. Study 2: Sample Details VariableSZ (N=20) Controls (N=18) AGE34.332.8 M:F18:216:2 English=1 st lang16 Smoker:Non-S15:57:11* Matrices (scaled score) 10.913.3** WM (% correct)73.191.3** *p<0.05; **p<0.01

26. Study 2: Patient Details Duration of illness10.6 yrs In- vs. out-patients10 vs. 10 Medicated20/20 SAPS Positive5.05 SANS Negative9.05 SANS Disorganised1.9 SANS Attentional Imp.2.8 Global Hallucinations2.2 Global Delusions2.9

27. Study 2: Personality OLIFE ScoreSZ (N=20) Controls (N=18) Positive (UnEx)14.98.2** Negative (IntAnh)10.65.9** Disorg. (CogDis)16.010.2* Other (ImpNon)8.29.5 *p<0.05; **p<0.01

28. Study 2: 1 st GLM Analysis of CL (no. correct) Within-subjects PHASE (first, second) Between-subjects Group (SZ vs control), set order

29. Study 2: Results 1 Main effect of group, p<0.005 p<0.05

30. Study 2: 2 nd GLM Analyses Within-subjects PHASE (first, second) Between-subjects Group (SZ vs control) Covariates (each separately) Matrices IQ WM accuracy Smoking (as factor) Validity?

31. Study 2: Results 2 Including IQ IQ p<0.05; Group p<0.05 Including WM Accuracy WM p<0.08; Group p<0.05 Including Smoking Smoking p>0.8; Group p=0.01 Group*Smoking p>0.4

32. Correlations with symptoms Ph1Ph2Ph1 +Ph2 Ph1 -Ph2 SAPS Positive 0.320.020.230.27 SANS Negative 0.01-0.19-0.110.16 SANS Disorganised 0.160.210.23-0.03 SANS Attentional Imp. -0.05-0.30-0.210.19 Global Hallucinations 0.270.000.180.23 Global Delusions 0.280.040.21 N=20; all ns p>0.15

33. Correlations with OLIFE in SZ Ph1Ph2Ph1 +Ph2 Ph1 -Ph2 OLIFE Positive (UnEX) 0.51*0.140.430.34 OLIFE Neg. (IntAnh) -0.31-0.11-0.27-0.19 OLIFE Disorg. (CogDis) 0.310.060.240.22 OLIFE Other (ImpNon) 0.50*0.080.380.37 N=20; all ns p>0.1; except *p<0.05; p=0.06

34. Correlations with OLIFE in Controls Ph1Ph2Ph1 +Ph2 Ph1 -Ph2 OLIFE Positive (UnEX) 0.20-0.050.17 OLIFE Neg. (IntAnh) -0.040.270.14-0.16 OLIFE Disorg. (CogDis) -0.05-0.07-0.09-0.00 OLIFE Other (ImpNon) -0.110.13-0.02-0.15 N=18; all ns p>0.4

35. Study 2: 3 rd GLM Analyses Within-subjects PHASE (first, second) Between-subjects Group (SZ vs control) Covariate OLIFE-UnEx Validity?

36. Study 2: Results 3 Including OLIFE:UnEx UnEx p<0.05; Group p<0.001 No sig effects involving PHASE For phase 1 performance only UnEx p<0.02; Group p<0.005 For phase 2 performance only UnEx p>0.5; Group p<0.02

37. Effect of OLIFE Unusual Experiences Effect of group removed from CL accuracy; r = +0.36, p<0.03

38. Effect of OLIFE Unusual Experiences Effect of group removed from CL accuracy; r = +0.08, p>0.5

39. 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

40. 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.