Psychosis proneness, working memory, and the developing brain : a multi-analytic approach

Abstract

Working memory (WM) ability matures throughout puberty and early adulthood. Deficits in WM are linked to risks of psychopathology such as schizophrenia, and there is a significant temporal overlap between the peak of first episode psychosis risk and WM maturation. The overall aim of the current dissertation is to understand late WM refinements in typical development, as well as its interplay with the subclinical psychosis phenotype, through a multi-analytic approach. Study 1 aimed to characterise the WM functional maturation process through this critical phase of cognitive development in a systematic review and coordinate-based meta-analyses of fMRI studies that mapped WM function in healthy adolescents (10-17 years) and young adults (18-30 years). Activation Likelihood Estimation analyses across all WM tasks revealed increased activation with age principally in part of the core WM network, while reductions were detected in more diffuse and potentially less mature neural networks. Studies 2 and 3 empirically explored WM and its association with ‘psychosis proneness’ in healthy Chinese adolescent twins. Psychosis proneness refers to unusual experiences and psychotic-like symptoms that do not meet the clinical threshold for psychotic disorders, as assessed with the validated questionnaire “Community Assessment of Psychic Experiences” (CAPE). Specifically, Study 2 applied a mixed linear model (MLM) approach to explain the correlation between WM and psychosis proneness. The MLM approach furthermore allowed disentanglement of familial- and unique environmental effects. Significant negative correlations were found between-twin pairs for WM and psychosis proneness scales, pointing to a strong familial effect. Additionally, the between-twin effect was dominant to the within-twin effects for WM and CAPE subscales, indicating that familial context effects (shared environmental influences and genetic predisposition) are of higher magnitude than unique environmental effects. While Study 2 aimed to differentiate between familial and unique environmental effects, Study 3 disentangled the familial effects further into shared environment and additive genetic effects by applying genetically-informed models. The best fitted bivariate model for the phenotypes ‘WM’ and ‘psychosis proneness’ showed both additive genetic effects and shared environmental effects. Results showed that 24-66% of the phenotypic correlation between verbal WM and CAPE scores was explained by shared genetic factors, and 31-61% was explained by shared environmental influences. 47-69% of the phenotypic correlation between visuospatial WM and CAPE was explained by shared genetic influences, and 14-45% was explained by shared environmental influences. Psychosis proneness is conceptualized as a subclinical manifestation of clinical psychosis with shared aetiology, studying cognitive correlates of psychosis proneness in adolescence - the peak of first episode psychosis risk - can therefore illuminate psychological risk mechanisms of psychosis while circumventing confounding illness-related variables in clinical samples. The strength of this dissertation lies in its multi-analytic approach, which allowed a multi-dimensional understanding of the under-researched late adolescence WM functioning, as well as its behavioural and genetic relationship with psychosis proneness. This moves us a step closer to the earlier detection and prevention of psychosis before behavioural deviance appears.