Progressive cortical change during adolescence in childhood-onset schizophrenia - A longitudinal magnetic resonance imaging study

Background: Adolescence provides a window to examine regional and disease-s pecific late abnormal brain development in schizophrenia. Because previous data showed progressive brain ventricular enlargement for a group of adoles cents with childhood-onset schizophrenia at 2-year follow-up, with no signi ficant changes for healthy controls, we hypothesized that there would be a progressive decrease in volume in other brain tissue in these patients duri ng adolescence. Methods: To examine cortical change, we used anatomical brain magnetic reso nance imaging scans for 15 patients with childhood-onset schizophrenia (def ined as onset of psychosis by age 12 years) and 34 temporally yoked, health y adolescents at a mean (SD) age of 13.17 (2.73) years at initial baseline scan and 17.46 (2.96) years at follow-up scan. Cortical gray and white matt er volumes were obtained with an automated analysis system that classifies brain tissue into gray matter, white matter, and cerebrospinal fluid and se parates the cortex into anatomically defined lobar regions. Results: A significant decrease in cortical gray matter volume was seen for healthy controls in the frontal (2.6%) and parietal (4.1%) regions. For th e childhood-onset schizophrenia group, there was a decrease in volume in th ese regions (10.9% and 8.5%, respectively) as well as a 7% decrease in volu me in the temporal gray matter. Thus, the childhood-onset schizophrenia gro up showed a distinctive disease-specific pattern (multivariate analysis of variance for change x region x diagnosis: F, 3.68; P = .004), with the fron tal and temporal regions showing the greatest between-group differences. Ch anges in white matter volume did not differ significantly between the 2 gro ups. Conclusions: Patients with very early-onset schizophrenia had both a 4-fold greater decrease in cortical gray matter volume during adolescence and a d isease specific pattern of change. Etiologic models for these patients' ill ness, which seem clinically and neurobiologically continuous with later-ons et schizophrenia, must take into account both early and late disruptions of brain development.