Intracranial and subcortical volumes in adolescents withearly-onsetpsychosis: A multisitemega-analysisfrom theENIGMAconsortium

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'sd= -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.