Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study.

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool. METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables. RESULTS: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses. CONCLUSION: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

Meta-analysis of longitudinal neurocognitive performance in people at clinical high-risk for psychosis.

Persons at clinical high-risk for psychosis (CHR) are characterised by specific neurocognitive deficits. However, the course of neurocognitive performance during the prodromal period and over the onset of psychosis remains unclear. The aim of this meta-analysis was to synthesise results from follow-up studies of CHR individuals to examine longitudinal changes in neurocognitive performance. Three electronic databases were systematically searched to identify articles published up to 31 December 2021. Thirteen studies met inclusion criteria. Study effect sizes (Hedges' g) were calculated and pooled for each neurocognitive task using random-effects meta-analyses. We examined whether changes in performance between baseline and follow-up assessments differed between: (1) CHR and healthy control (HC) individuals, and (2) CHR who did (CHR-T) and did not transition to psychosis (CHR-NT). Meta-analyses found that HC individuals had greater improvements in performance over time compared to CHR for letter fluency (g = -0.32, p = 0.029) and digit span (g = -0.30, p = 0.011) tasks. Second, there were differences in longitudinal performance of CHR-T and CHR-NT in trail making test A (TMT-A) (g = 0.24, p = 0.014) and symbol coding (g = -0.51, p = 0.011). Whilst CHR-NT improved in performance on both tasks, CHR-T improved to a lesser extent in TMT-A and had worsened performance in symbol coding over time. Together, neurocognitive performance generally improved in all groups at follow-up. Yet, evidence suggested that improvements were less pronounced for an overall CHR group, and specifically for CHR-T, in processing speed tasks which may be a relevant domain for interventions aimed to enhance neurocognition in CHR populations.