Abstract

BackgroundNeurostructural alterations are often reported in first episode of psychosis (FEP), but there is heterogeneity in the direction and location of findings between individual studies. The reasons for this heterogeneity remain unknown. Obesity is disproportionately frequent already early in the course of psychosis and is associated with smaller brain volumes. Thus, we hypothesized that obesity may contribute to brain changes in FEP.MethodWe analyzed MRI scans from 120 participants with FEP and 114 healthy participants. In primary analyses, we performed voxel-based morphometry (VBM) with small volume corrections to regions associated with FEP or obesity in previous meta-analyses. In secondary analyses, we performed whole-brain VBM analyses.ResultsIn primary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in a) left fronto-temporal region (pTFCE = 0.008) and b) left postcentral gyrus (pTFCE = 0.043). When controlling for FEP, BMI was associated with lower GM volume in left cerebellum (pTFCE < 0.001). In secondary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in the a) cerebellum (pTFCE = 0.004), b) left frontal (pTFCE = 0.024), and c) right temporal cortex (pTFCE = 0.031). When controlling for FEP, BMI was associated with lower GM volume in cerebellum (pTFCE = 0.004). Levels of C-reactive protein, HDL and LDL-cholesterol correlated with obesity related neurostructural alterations.ConclusionsThis study suggests that higher BMI, which is frequent in FEP, may contribute to cerebellar alterations in schizophrenia. As previous studies showed that obesity-related brain alterations may be reversible, our findings raise the possibility that improving the screening for and treatment of obesity and associated metabolic changes could preserve brain structure in FEP.

Highlights

  • Neurostructural alterations are frequently reported already early in the course of schizophrenia (SZ) and may contribute to worse psychiatric outcomes [1, 2]

  • We further explored the links between clinical or obesity related biochemical alterations and the brain changes associated with first episode of psychosis (FEP) or body mass index (BMI)

  • When focusing on regions previously associated with FEP or obesity, we found lower gray matter (GM) volume in FEP versus healthy participants, while controlling for BMI, in a) cluster including left IFG-STG-temporal pole-insula-operculum (Cohen’s d = 0.55; tmax = 4.19; pTFCE = 0.008; 395 voxels), b) left postcentral gyrus (Cohen’s d = 0.43; tmax= 3.34; pTFCE = 0.043; 13 voxels)

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Summary

Introduction

Neurostructural alterations are frequently reported already early in the course of schizophrenia (SZ) and may contribute to worse psychiatric outcomes [1, 2] Participants in their first episode of psychosis (FEP) typically show smaller gray matter (GM) volumes in frontal, temporal, and insular lobes, there is heterogeneity in the direction and location of findings between individual studies [3,4,5]. The reasons for this heterogeneity and the origins of neurostructural alterations in FEP remain unknown. We hypothesized that obesity may contribute to brain changes in FEP

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