Impaired Functioning in Schizophrenia: Models, Mechanisms and Measurement

1. Impaired Functioning in Schizophrenia: Models, Mechanisms and Measurement Dr Kathryn Greenwood Department of Psychology, University of Sussex & Sussex Partnership NHS Foundation Trust

2. Overview • Personal Accounts • Theories of symptoms, cognition and function in schizophrenia • Studies • 1 Executive impairment profiles in Schizophrenia (JINS) • 2 Executive impairments and symptoms models (Schiz Bull) • (including in materials in preparation) • 3 Cognitive impairments and Awareness (Schiz Bull) • 4 Genes and outcome (Neuroscience letters) • 5 VR as a measurement tool (in preparation) • Clinical implications and future directions

3. Personal Accounts

4. “My concentration is very poor. I jump from one thing to another. If I am talking to someone they only need to cross their legs or scratch their head and I am distracted and forget what I was saying.” McGhie and Chapman, 1961

5. “I was looking at A or B for some subjects now I’m looking at C or D if I’m lucky.” “Memory loss is the new thing that’s bothering me.” “I have low concentration” “I’m coming to terms with the fact that I have got a learning difficulty.” Michael, Aged 16 years Inside my head - Channel 4, June 2002

6. Work “I want to be able to do things that other people do, like have a boyfriend and a job …” Social Functioning“I want to have friends” Community Function “I want to be able to cook and eat when I want” “I want to live in my own place not a hostel”

7. Theoretical Background

8. Crow 1980

9. Liddle 1987, 1991

10. Baddeley’s Working Memory Model Phonological Loop Visuospatial Sketchpad Store Central Executive Baddeley and Hitch, 1978; Baddeley and Della Sala 1996

11. Goldman-Rakic 1987 Adjacent modality-specific working memory systems in DLPFC with own control systems: a fundamental impairment in schizophrenia

12. Shallice’s Supervisory Attentional System • Automatic contention scheduling Until • i) novel environment • ii) requirement to inhibit one strong or several weak competing schema • New Schema construction • Implementation in working memory • Monitoring and Inhibition Norman and Shallice 1982; Shallice and Burgess 1992; 1996

13. Frith’s Cognitive Neuropsychology of Schizophrenia 1992 Three main (theory of mind) disorders: • Disorders of willed intentions (action driven by intention) • Disorders of self-monitoring • Monitoring the Intentions of others Negative symptoms = absence of initiation of willed intentions, plans and strategies and impaired monitoring of others so missed communication cues Thought disorder (incoherence of behaviour/affect) = poor inhibition of stimulus driven responses by intentions, as well as impaired self monitoring of communication goal to output and impaired monitoring of listener’s understanding

14. Do Specific Cognitive deficits predict specific domains of function? Velligan et al. 2000

15. Neurocognition and function: Are we measuring the right stuff? Green 2000 Card Sort Community/daily activities learning potential and skill acquisition as mediators of functional outcome Verbal fluency Social problem solving/ instrumental skills Immediate verbal memory Psychosocial skill acquisition

16. Green’s conclusions 2000 ‘We have learned whether but not HOW neurcognition is related to functional outcome?’ Need to know what mediates relation between neurocognition and outcome? • Processes (learning potential) that underlie the ability to acquire and perform life skills • Social cognition

17. There is a need for new cognitive models of negative symptoms and function in order to improve functional outcomes

18. Lincoln et al. (in press) Negative symptoms associated with Impaired Social Cognition: difficulties in ToM lower self-esteem less self-serving bias Negative self-concepts related to interpersonal abilities Dysfunctional acceptance beliefs. Some social cognitive impairments (ToM) were associated with negative symptoms only in people with low self-esteem. So self-concepts related to social abilities, dysfunctional beliefs and global self-worth alone and in interaction with skill-deficits are associated with negative symptoms

19. Rector, Beck and Stolar (2005) • Low expectancies for pleasure, success, acceptance & perception of limited resources play a major role in the formation of negative symptoms • Dysfunctional performance beliefs (e.g. If I fail partly, it is as bad as being a complete failure) associated with negative symptoms • Indirect pathways between functional capacity (cognitive impairment), dysfunctional performance beliefs, and negative symptoms and real-world functioning

20. Past and current studies

21. Research Aims To understand the mechanisms through which bio-psychosocial factors including • Gene markers • Phenomenology of schizophrenia • Cognitive function & • Psychological function (thinking, mood and behaviour) Affect functional outcome in schizophrenia

22. Study 1 Aims Categorisation of sub-groups by neuropsychological profile in all cases confounds the relationship between symptoms and chronicity. Aims To explore the severity and profile of executive functioning in relation to disorganisation and psychomotor poverty and simultaneously To investigate the early and late profiles in first episode and chronic schizophrenia. Hypothesis Chronicity will associate with similar but more severe impairment Disorganisation will associate with broad executive deficit Psychomotor poverty with impaired working memory and response initiation

23. Study 1 Measures • working memory • Digit span, word span, executive golf • planning and strategy formation • Tower of london, hayling and executive golf strategy scores • response initiation • Verbal fluency • response inhibition • Hayling test and complex reaction time test • IQ • WAIS-R and NART-R

24. Novel measures – the question • To assess similar processes in cognitive & function task • Working memory example • 3KA27 • Crunchy Green salad 250g £1.09 • Crunchy Green salad 500g £1.24 • Mixed Salad 250g £1.15 • Caesar Salad 120g £ 1.05

25. Example using Search Strategy

26. Novel measures – the answer • Example using Working Memory • 3KA27 237AK • Caesar Salad 120g £ 1.05 Crunchy Green salad 250g £1.09 • Mixed Salad 250g £1.15 • Crunchy Green salad 500g £1.24

27. Example using Search Strategy

28. Study 1 Analysis Group differences in executive function MANCOVA’s controlling for WAIS IQ Executive profiles • Converted to z-scores and compared using generalised estimating equations (GEE). Group as between and executive function as within subject factor Specific islets of strength/deficit • Domain score compared to average of all others while holding IQ constant

29. Study 1 Symptom study

30. Study 1 Chronicity study

31. Distinct profiles and poorer performance in schizophrenia/and disorganisation than controls/pp

32. Parallel non-flat profiles and poorer performance in chronic schizophrenia (and FE) compared to controls

36. Study 1 Conclusions • Schizophrenia - characterised by a single executive profile that reflects the make up of symptoms (psychomotor poverty / disorganisation) but not chronicity • Parallel but attenuated profile at first episode due to incorporation of those with intact function • Disorganisation - broad impairment profile incorporating planning and working memory • Psychomotor poverty - particularly impaired response initiation • Predictive power of either symptoms or cognition on outcome is short lived but stable symptom-cognition markers should be targets of intervention

37. Study 2 • Schizophrenia - characterised by a single executive profile that reflects the make up of symptoms (psychomotor poverty / disorganisation) but not chronicity • Parallel but attenuated profile at first episode due to incorporation of those with intact function • Disorganisation - broad impairment profile incorporating planning and working memory • Psychomotor poverty - particularly impaired response initiation • Predictive power of either symptoms or cognition on outcome is short lived but stable symptom-cognition markers should be targets of intervention

39. Negative Symptoms matter in the Leap from Cognition to Community Function in Schizophrenia: Implications for Intervention Dr K Greenwood, Dr S Landau, Professor T Wykes Department of Psychology, Institute of Psychiatry, London, UK. e-mail: k.greenwood@iop.kcl.ac.uk

40. Introduction • People with schizophrenia and negative symptoms have poor functioning (occupation, community and daily living skills) • Poor functioning is a source of distress for both people with schizophrenia and their families

41. Negative Symptoms associated with Community Function • Negative symptoms (flat affect, poverty of speech, apathy) affect function: • Only Indirectly through link with Cognition • Independently

42. Cognitive Impairments associated with Community Function • Executive function predicts Community function, Occupation, Daily living • Working Memory predicts Occupation • Global cognition predicts Daily living • Cognition is a stronger predictor than symptoms (Green 2000)

43. Cognitive Impairments associated with negative symptoms Negative symptoms: Linked theoretically with : Executive function and Working memory Initiation/generation of strategies (Frith) Working memory (Goldman-Rakic) Linked Empirically with: Response Initiation (Franke et al. 1993) Immediate/working memory (Pantelis et al 2001) Focused/switching attention (Buchanan et al 1994) Initiation/working memory/strategy use (Greenwood 2000)

44. Objective • To investigate specific relationships between negative symptoms, executive/working memory functions and community function and in particular to investigate the independent effect of negative symptoms • Reducing confounding of negative symptoms and low IQ • Using process approach and theoretically driven framework • Also using a novel measure to directly assess community function

45. Design • Cross sectional Comparison: 22 Healthy controls 28 Schizophrenia & negative symptoms balanced general 22 Schizophrenia & no negative symptoms cognitive impairment • Balancing: Age, Sex, Premorbid IQ, • Predictors: working memory, initation, inhibition, strategy, symptoms • Analysis: Identify individual associations to function, interactions, and final regression model

46. The measure A test of supermarket shopping Skills • Participants had to select 10 items from a • shopping list. • Measures were taken of: • accuracy (items correct) • Efficiency (time/route length) • Redundancy (no. aisles entered above minimum) • Strategy • (adapted from Test of Grocery Shopping Skills, Hamera and Brown 2000)

47. Research Questions • Is directly assessed community function more impaired in people with schizophrenia and negative symptoms (when directly assessed and without IQ confound) • Do specific executive processes predict specific community functions (working memory-accuracy; strategy-strategy) • Do the associations differ in different symptom groups (use of theoretical rationale to investigate moderator effect of negative symptoms)

48. Subject Characteristics

49. Statistical Analyses • Association Analyses (GLR – with binomial, Poisson, normal distribution)* Stage 1: Identify individual associations (cognition x function) Stage 2: Identify individual interactions (cognition x symptom group x function) Stage 3: Conduct final regression model Premorbid IQ controlled

50. Poorer strategy, working memory, initiation in negative group Verbal fluency initiation Verbal working memory score Spatial Strategy Score 40 4 12 35 10 30 3 8 25 6 20 2 15 4 10 1 2 5 0 0 0 control neg non-neg neg control non-neg control non-neg neg