Positive schizotypy : a proposed endophenotype for psychosis in neurological disorders

In the current thesis, a model whereby the fully dimensional expression of positive schizotypal (PS) personality traits represents a psychological and biological diathesis that would predict psychotic decompensation in states of neurological stress was theoretically conceptualised and empirically validated. To our knowledge, this is the first piece of work to fully reconcile a predispositional psychological and biological susceptibility within a diathesis stress model of neurological psychosis. Whilst previous studies have assessed psychological or biological vulnerabilities to the development of psychotic symptoms in neurodegenerative and functional models, to date no individual study has theoretically or experimentally combined these features.The predictive ability of PS for neurological psychosis was validated on interdependent neuroanatomical, psychological, emotional, cognitive and symptomatic levels. The validity of PS as an endophenotype for neurological psychosis was tested across several behavioural and neuroimaging studies. The most compelling cognitive evidence for the endophenotype‘s validity was the finding that PS is associated with a bias to make false positive confabulationary style memories for psychosis congruent words. This finding converges with behavioural and anatomical evidence for a relationship between confabulation and delusions in pathological populations and was supported by the neuroimaging study of the individual differences of PS traits in healthy young individuals undertaken for the current thesis. Individual differences in schizotypal traits in normal individuals were found to be reflected endophenotypically in the structure of the brain in the bilateral but predominantly right frontal regions that have been anatomically and behaviourally related to psychosis in previous studies. The endophenotype was also validated as predicting psychosis in single case studies of patients with various diagnoses and was behaviourally and anatomically associated with the psychotic reactions of patients with Parkinson‘s disease to Levodopa medication. The validation studies suggest that, independent of aetiology, psychosis appears to be supported by bilateral but predominantly right sided frontal and limbic regions. The majority of individuals with this non-standard but dimensional trait will not decompensate into psychosis. However, the clinical data suggests that when individuals with high PS traits are under the duress of a significant affective, neurodegenerative or neuropharmacological stressor, the prominent symptom will be psychosis.