Identifying neuroanatomical subtypes of psychosis

by Alana Shepherd

Institution: University of New South Wales
Department: Psychiatry
Year: 2014
Record ID: 1054016
Full text PDF: http://handle.unsw.edu.au/1959.4/53826


Background: The quantity and heterogeneity of structural magnetic resonance imaging (sMRI) studies in schizophrenia present a challenge to their meaningful interpretation. This thesis sought to synthesise the available literature on neuroanatomical alterations in people with schizophrenia, and explore brain volume differences among subgroups of schizophrenia defined on the basis of cognitive ability. The thesis also investigated whether analogous cognitive subgroups extending across the psychosis-mood spectrum (including bipolar-I disorder) may be differentiated by brain volume. Methods: Meta-review of the existing sMRI literature was conducted using electronic databases. Random-effects meta-analysis was used to statistically collate studies reporting insular cortex volume in schizophrenia. Subsequent analysis of structural imaging data from two separate samples explored differences in grey and white matter volume among cognitive subtypes of psychotic disorder relative to controls. Subgroups within a large schizophrenia sample were allocated to ‘cognitively spared’ (CS;; N=157) or ‘cognitively deficit’ (CD;; N=106), compared to healthy controls (N=181). Subsequently, a mixed sample of schizophrenia and bipolar-I disorder was stratified into ‘executively spared’ (ES;; N=38) and ‘executively deficit’ subgroups (ED;; N=32) to assess differences in grey and white matter volume. Results: Critical synthesis of the sMRI literature identified limited high quality evidence for widespread regional grey and white matter aberration in schizophrenia. Specific assessment of insular cortex identified moderate volume reductions, with large heterogeneity not explained by age, sex, illness duration, medication, whole brain volume, or hemisphere. Assessment of cognitive subtypes of schizophrenia identified distinct neuroanatomical profiles of each group relative to controls, with the cognitively impaired group showing more diffuse brain volume reductions. Assessment of the diagnostic specificity of these findings identified no differences between groups defined by bipolar-I disorder and schizophrenia diagnoses, but similarly diffuse volume deficits across the psychosis-mood spectrum in the executively impaired subgroup. Conclusions: Stratification according to intermediate cognitive phenotypes identified trans-diagnostic subtypes that exhibited markedly discrepant brain aberrations and clinical features. These findings provide insight into potential neuropathological regions, and suggest the existence of discrete illness types who may be associated with divergent neurodevelopmental or genetic vulnerabilities.