Progressive Brain Volume Loss During Adolescence in Childhood-Onset Schizophrenia

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Abstract
Method: A total of 131 brain magnetic resonance imaging scans were acquired for 60 subjects with childhood-onset schizophrenia (mean age=14.5 years, SD= 2.5), and 140 scans were acquired for 64 matched healthy comparison subjects. One or more follow-up scans were ac- quired at approximately 2-year intervals for 39 subjects with childhood-onset schizophrenia and 43 healthy subjects. Developmental trajectories for total and regional brain volumes were examined in relation to age by using polynomial growth models and data from all avail- able scans. The rate of gray matter reduc- tion in patients with childhood-onset schizophrenia was examined in relation to developmental and clinical measures by using stepwise regression. Results: Rates of brain volume reduction were significantly higher for patients with childhood-onset schizophrenia than for healthy comparison subjects. In child- hood-onset schizophrenia, the rate of gray matter reduction was related to pre- morbid impairment and baseline severity of clinical symptoms but not to gender, ethnicity, or age at onset of the disorder. Unexpectedly, greater clinical improve- ment was significantly related to a higher rate of gray matter reduction. Longitudi- nal trajectories suggested that the rate of cortical loss plateaus during adolescence. Conclusions: Striking loss of cerebral gray matter is seen through adolescence in patients with childhood-onset schizo- phrenia. The rate of reduction was related to premorbid impairment and baseline symptom severity, but it may also be in part a plastic response to illness.

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