Ben Wiffen

Failures of metacognition and lack of insight in neuropsychiatric disorders

Lack of insight or unawareness of illness are the hallmarks of many psychiatric disorders, especially schizophrenia (SCZ) and other psychoses and could be conceived of as a failure in metacognition. Research in this area in the mental health field h as burgeoned with the development and widespread use of standard assessment instruments and the mapping out of the clinical and neuropsychological correlates of insight and its loss. There has been a growing appreciation of the multi-faceted nature of the concept and of the different ‘objects’ of insight, such as the general awareness that one is ill, to more specific metacognitive awareness of individual symptoms, impairments and performance. This in turn has led to the notion that insight may show modularity and may fractionate across different domains and disorders, supported by work that directly compares metacognition of memory deficits and illness awareness in patients with SCZ, Alzheimers disease and brain injury. The focus of this paper will be on the varieties of metacognitive failure in psychiatry, particularly the psychoses. We explore cognitive models based on self-reflectiveness and their possible social and neurological bases, including data from structural and functional MRI. The medial frontal cortex appears to play an important role in self-appraisal in health and disease.

Metacognition, mindreading, and insight in schizophrenia

Mindreading in schizophrenia has been shown to be impaired in a multitude of studies. Furthermore, there is increasing evidence to suggest that metacognition is damaged as well. Lack of insight, or the inability to recognise ones own disorder, is an example of such a failure. We suggest that mindreading and metacognition are linked, but separable.

F68. PREMORBID IQ, EDUCATIONAL LEVEL AND JUMPING TO CONCLUSIONS AS PREDICTORS OF CLINICAL OUTCOME AT FIRST ONSET OF PSYCHOSIS OVER THE NEXT 4 YEARS: THE GAP STUDY

Abstract Background Cognition and more recently social cognition, have been shown to be a strong predictor of clinical and functional outcome in psychosis. Jumping to Conclusions (JTC), which is defined as the proneness to require less information before forming beliefs or making a decision, has been related to the formation and maintenance of delusions. However, its relevance to longer-term outcome is unclear. On the other hand, there is evidence in the literature to suggest differences of patterns in clinical outcome and service based ethnicity. Using data from the GAP case-control study of first-episode psychosis (FEP), we set out to test whether the premorbid IQ, educational level and presence of JTC would predict poor clinical outcome at 4 year controlling for ethnicity. Methods 431 FEP patients were assessed with the positive and negative syndrome scale (PANSS) and Global Assessment of Functioning (GAF). Premorbid IQ was measured by the National Adult Reading Test (NART) scale, probabilistic reasoning “Beads” task was applied and educational levels were recorded alongside with socio-occupational variables at the time of recruitment. Follow-up data over an average period of 4 years were obtained from the electronic psychiatric clinical records in the South London and Maudsley NHS Foundation Trust (SLaM); including items concerning clinical course and outcomes (remission, intervention of police, use of involuntary treatment – the Mental Health Act (MHA) -, and inpatient days). We build different regression models using separately premorbid IQ, education level and JTC as predictors for each clinical outcome, both unadjusted and adjusted by ethnicity, age and gender. Results Higher educational level was predictor of clinical remission [adjusted OR=1.9, 95% confidence interval (CI) 1.2–3, p=0.005]. FEP who presented JTC at baseline were more likely during the follow up period to be detained under the MHA [adjusted OR=11.23, 95% confidence interval (CI) 2.64–47.76, p=0.001], require intervention by the police (adjusted OR=10.76, 95% CI 2.4–48.26, p=0.002) and have longer admissions (adjusted IRR=4.04, 95% CI 1.43–11.36, p=0.008). We couldn’t find any predictor effect for clinical outcome for premorbid IQ. The association with level of education and JTC was not accounted for by socio-demographic variables including ethnicity. Discussion Although we did not find association with premorbid IQ, educational level as indirect proxy of neurocognition showed a predictor effect for clinical remission. JTC in FEP is associated with serious subsequent consequences in terms of social disturbance and a poor therapeutic alliance. Our findings raise the question of whether the implementation of specific interventions to reduce JTC, such as Metacognition Training, may be a useful addition in early psychosis intervention programs.

Cognitive impairment and subjective time in schizophrenics

Background: The large variation in individual clinical responses to antipsychotic treatment hampers the management of psychotic disorders. Genetic factors are considered a main cause of this variation. Pharmacogenetics studies have demonstrated significant associations between several candidate genes (a.o. D2, D3, 5HTR2A and 5HTR2C, GRM3, COMT and MTHFR) and the response to antipsychotic drugs. The present study investigates the effect of 12 polymorphisms for an association with antipsychotic treatment response in patients with a psychotic disorder. Methods: 335 Caucasian patients with a non-affective psychotic disorder using antipsychotics were included. All patients participated in the longitudinal GROUP-study in The Netherlands. We genotyped 12 SNPs in 7 candidate genes (DRD2: TaqI-A, TaqI-D, -141-C, C957T; DRD3: Ser9Gly; HTR2A: 102-T/C, His452Tyr; HTR2C: Cys23Ser, -759-T/C; COMT: Val108/158Met; MTHFR: 677-C/T, GRM3: rs274622) using standard protocols. Polymorphisms were based on previous studies showing associations with treatment response. The Clinical Global Impression- Schizophrenia scale was cross-sectionally used to assess improvement in positive psychotic symptoms since the start of current antipsychotic treatment. Ordinal regression was used to test for an association between polymorphisms and improvement in positive symptoms. All polymorphisms were tested in an additive model, with minor allele dose as the dependent variable. Results: Ninety percent of the patients used atypical antipsychotics, with olanzapine (31%) and risperidone (29%) being the most prescribed drugs. Ser9Gly of the dopamine D3 receptor gene (P value .029) and 677-C/T of MTHFR (P value .029) were tested significant. Gly carriers and T-carriers, respectively, showed better clinical improvement on the positive scale. All other polymorphisms did not show any association with treatment response (all P values >.10). Conclusion: We were able to replicate only two of the previously reported associations between polymorphisms and treatment response. Heterogeneity in patient samples and outcome variables as well as publication bias and false positive findings may all play a role in lack of replication, found in our study, as in others. The direction of the associations presented here in D3 (Ser9Gly) and MTHFR (677-C/T) are in line with previous association studies in Caucasian patients. These polymorphisms may be of value for predicting clinical response.

S06-04 Skunk and psychosis in South East London

Background Epidemiological studies have reported that the increased risk of developing psychosis in cannabis users is dose related. In addition, experimental research has shown that the active constituent of cannabis responsible for its psychotogenic effect is Delta-9-Tetrahydrocannabinol (THC) (Murray et al, 2007). Recent evidence has suggested an increased in potency (% TCH) in the cannabis seized in the UK (Potter et al, 2007). Hypothesis We predicted that first episode psychosis patients are more likely to use higher potency cannabis and more frequently than controls. Methods We collected information concerning socio-demographic, clinical characteristics and cannabis use (age at first use, frequency, length of use, type of cannabis used) from a sample of 191 first-episode psychosis patients and 120 matched healthy volunteers. All were recruited as part of the Genetic and Psychosis (GAP) study which studied all patients who presented to the South London and Maudsley Trust. Results There was no significant difference in the life-time prevalence of cannabis use or age at first use between cases and controls. However, cases were more likely to be regular users (p=0.05), to be current users (p=0.04) and to have smoked cannabis for longer (p=0.01). Among cannabis users, 86.8% of 1st Episode Psychosis Patients preferentially used Skunk/Sinsemilla compared to 27.7% of Controls. Only 13.2 % of 1st Episode psychosis Patients chose to use Resin/Hash compared to 76.3% of controls. The concentration of TCH in these in South East London, ranges between 8.5 and 14 % (Potter et al, 2007). Controls (47%) were more likely to use Hash (Resin) whose average TCH concentration is 3.4% (Potter et al, 2007). Conclusions Patients with first episode psychosis have smoked higher potency cannabis, for longer and with greater frequency, than healthy controls.