Cognition in individuals at familial and clinical risk for severe mental illness

Abstract

Severe mental illness (SMI) includes schizophrenia, bipolar disorder and severe and chronic major depressive disorder. SMI typically onsets early in the lifespan and causes significant impairments in functioning. Cognitive function has been proposed as a potential neurodevelopmental indicator of risk for development of SMI. However, the relationships between cognition and risk for onset of SMI in individuals at familial risk are not fully understood. This thesis aimed to investigate cognition in individuals at familial and clinical risk for SMI. In study 1, I examined cognition in 360 children and youth, and found that offspring of parents with psychotic SMI performed significantly worse on overall cognition, verbal intelligence, verbal working memory, processing speed, verbal learning and memory, verbal fluency and sustained attention. Sons and daughters of parents affected with non-psychotic SMI performed significantly worse than controls on verbal intelligence, visual memory and decision-making. The findings of study 1 indicate that mild cognitive impairment may be a marker of transdiagnostic familial risk for any form of SMI. Additional deficits in verbal cognition, verbal memory, verbal fluency, processing speed, and sustained attention may be markers of familial risk for psychotic SMI. In study 2, I investigated cognition as a potentially important indicator of neurodevelopmental disturbance and its association with propensity to experience psychotic symptoms in a cohort of 295 youth, 71 of whom reported definite psychotic symptoms. After accounting for age, sex and familial clustering, psychotic symptoms were associated with worse performance in overall cognition, verbal intelligence, visual memory, decision-making, spatial working memory, and set shifting. In study 3, I investigated cognitive performance as a potential etiological mechanism in the development of severe mental illness. In a 6-year longitudinal cohort of 309 youth, I found that onset of SMI was predicted by reduced overall cognitive performancce, verbal intelligence, and sustained attention. These findings indicate that deficits in cognitive ability are associated with familial risk for psychotic SMI, propensity to experience psychotic symptoms, and new onsets of severe mental illness diagnoses in offspring. Impairments in overall cognition may be indicators of risk and targets for pre-emptive early interventions.