Structural brain abnormalities at different stages during the development of psychosis

Abstract

Structural brain changes in psychosis have been suggested as both a biomarker of the disorder and even a predictor of clinical outcome. However, it remains unclear how structural brain changes are linked to the different stages of developing psychosis. In my thesis I investigated gray matier (GM) volume changes across three distinct phases of developing psychosis and tried to address two key questions; 1) When do structural brain changes first appear in the development of psychosis; and 2) Are certain brain regions consistently affected, or do the abnormalities spread to different areas of the brain as the illness evolves through different stages. Firstly, in Chapter 1, I have provided a background to the study cohorts and methodologies used in the thesis. In Chapter 2, I conducted a comprehensive brain morphometry analysis using the ENIGMA-VBM tool in a large sample from the ENIGMA early onset psychosis (EOP) cohort. The study comprised 482 EOP and 469 healthy controls (HC) and provided robust evidence for widespread GM reduction throughout the brain in psychosis. Based on the ENGIMA EOP results and other recent neuroimaging literature in psychosis, I selected 5 regions of interest that were particularly affected in psychosis and likely representative of pathological changes in the disorder's progression. These regions of interest included total GM, anterior cingulate cortex (ACC), hippocampus, fusiform gyrus, and insula. In Chapter 3, the volume of these regions was examined in those at clinical high risk (CHR) for psychosis from the EU-GEI high risk study. In individuals who later develop psychosis, CHR represents the prodromal stage of the illness.

The study comprised 226 CHR individuals and 65 HC. In CHR individuals compared to HC I found reduced total GM and fusiform gyrus volume at baseline and no differences were observed in the ACC, hippocampus and insula. I further explored the relationship between baseline brain volumes and longitudinal positive and negative symptoms and functioning.

Low total GM and hippocampus volume were associated with higher positive symptoms in CHR individuals over time. In addition, low hippocampal volume was predictive of later transition to psychosis. In Chapter 4 I investigated a putative earlier stage of psychosis, in children who reported psychotic-like experiences, developmental delay or a family history of schizophrenia (CHADS study). This study was a longitudinal MRI analysis of 53 at-risk children and 35 typically developing children (TD). Children with psychotic like experiences and developmental delay had a similar trajectory compared to TD. For children with a family history of schizophrenia, there were differences in the trajectory of total gray matier volume, hippocampus, insula and middle temporal gyrus over the four-year follow-up period. Finally in Chapter 5 I extensively discuss the 3 studies and link the findings to relevant literature, highlighting differences and commonalities in the results and how these studies taken together can answer the two key questions and provide new insight into brain structural changes in the development of psychosis.

Date of Award	1 Jan 2025
Original language	English
Awarding Institution	King's College London
Supervisor	Matthew Kempton (Supervisor) & Philip McGuire (Supervisor)