Longitudinal investigation of brain alterations in children putatively at risk of developing schizophrenia may identify early markers of pathophysiology associated with vulnerability for the disorder.

Children aged 9–12 years with multiple antecedents of schizophrenia (psychotic-like experiences; speech and/or motor delays; and social, emotional, and/or behavioral difficulties; ASz, n = 31), with a family history of schizophrenia/schizoaffective disorder (FHx, n = 21), and typically developing children (TD, n = 35) were recruited through community screening using questionnaires. T1-weighted structural MRI scans were obtained at baseline and after approximately 2 and 4 years of follow-up, and processed using the FreeSurfer longitudinal pipeline. Across these 3 assessment waves, total gray matter (GM) and white matter (WM) volume, and regional GM volumes in 12 regions of interest, were compared among the groups using linear mixed models.

Children were aged 11.21 (±1.61) years at baseline and the average lapse-of-time between each assessment was 1.76 (±0.36) years. The ASz group exhibited consistently higher total WM volume (b = 29.45) compared to the TD group, with no statistically significant time-related volumetric WM or GM differences in any region. The FHx group also demonstrated higher total WM volume (b = 36.49), and time-related total and regional GM volume changes were observed; however, these effects were attenuated after correction.

Global and regionally specific brain abnormalities distinguished children with different risk profiles for schizophrenia relative to their typically developing peers. Follow-up is required to determine how these changes may relate to later schizophrenia.