Abstract

Early‐onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early‐onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early‐onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early‐onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed‐effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = −0.39) and hippocampal (d = −0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early‐onset schizophrenia (d = −0.34) and affective psychosis (d = −0.42), and early‐onset schizophrenia showed lower hippocampal (d = −0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = −0.42). The findings demonstrate a similar pattern of brain alterations in early‐onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early‐onset psychosis.

Highlights

  • Early-onset psychosis (EOP) disorders, defined as psychotic disorders with onset of the first psychotic episode before age 18 years, affect 0.05–0.5% of the population (Boeing et al, 2007; Dalsgaard et al, 2019; Gillberg, Wahlström, Forsman, Hellgren, & Gillberg, 1986; Sikich, 2013), and have a heterogeneous clinical presentation

  • With the exception of some prior multisite studies (Arango et al, 2012; Fraguas, Díaz-Caneja, PinaCamacho, Janssen, & Arango, 2016; Reig et al, 2011), structural brain magnetic resonance imaging (MRI) studies in EOP are limited by small sample sizes and low statistical power, typically including fewer than 50 patients

  • In this mega-analysis, we found a structural brain signature characterized by significantly lower ICV and hippocampal volumes, and higher caudate and pallidum volumes in EOP compared to healthy controls

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Summary

Introduction

Early-onset psychosis (EOP) disorders, defined as psychotic disorders with onset of the first psychotic episode before age 18 years, affect 0.05–0.5% of the population (Boeing et al, 2007; Dalsgaard et al, 2019; Gillberg, Wahlström, Forsman, Hellgren, & Gillberg, 1986; Sikich, 2013), and have a heterogeneous clinical presentation. With the exception of some prior multisite studies (Arango et al, 2012; Fraguas, Díaz-Caneja, PinaCamacho, Janssen, & Arango, 2016; Reig et al, 2011), structural brain magnetic resonance imaging (MRI) studies in EOP are limited by small sample sizes and low statistical power, typically including fewer than 50 patients To overcome these limitations, the Enhancing Neuro Imaging Genetics through Meta Analysis (ENIGMA; http://enigma.ini.usc.edu) Early-onset Psychosis Working Group was established, and this first ENIGMA-EOP study of intracranial and subcortical brain volumes includes data from 11 participating sites. It is still not clear how similar brain structural alterations in EOP are to those of adult-onset psychosis, or to other neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD)

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