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A Longitudinal Magnetic Resonance Imaging Study

Judith L. Rapoport, MD; Jay N. Giedd, MD; Jonathan Blumenthal, MA; Susan Hamburger, MA, MS; Neal Jeffries, PhD; Tom Fernandez; Rob Nicolson, MD; Jeff Bedwell; Marge Lenane, MSW; Alex Zijdenbos, PhD; Tomás Paus, MD, PhD; Alan Evans, PhD

Arch Gen Psychiatry. 1999;56:649-654.

Background  Adolescence provides a window to examine regional and disease-specific late abnormal brain development in schizophrenia. Because previous data showed progressive brain ventricular enlargement for a group of adolescents with childhood-onset schizophrenia at 2-year follow-up, with no significant changes for healthy controls, we hypothesized that there would be a progressive decrease in volume in other brain tissue in these patients during adolescence.

Methods  To examine cortical change, we used anatomical brain magnetic resonance imaging scans for 15 patients with childhood-onset schizophrenia (defined as onset of psychosis by age 12 years) and 34 temporally yoked, healthy 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 matter volumes were obtained with an automated analysis system that classifies brain tissue into gray matter, white matter, and cerebrospinal fluid and separates 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 the childhood-onset schizophrenia group, there was a decrease in volume in these regions (10.9% and 8.5%, respectively) as well as a 7% decrease in volume in the temporal gray matter. Thus, the childhood-onset schizophrenia group showed a distinctive disease-specific pattern (multivariate analysis of variance for changexregionxdiagnosis: F, 3.68; P=.004), with the frontal and temporal regions showing the greatest between-group differences. Changes in white matter volume did not differ significantly between the 2 groups.

Conclusions  Patients with very early-onset schizophrenia had both a 4-fold greater decrease in cortical gray matter volume during adolescence and a disease-specific pattern of change. Etiologic models for these patients' illness, which seem clinically and neurobiologically continuous with later-onset schizophrenia, must take into account both early and late disruptions of brain development.

From the Child Psychiatry Branch, National Institute of Mental Health (Drs Rapoport, Giedd, and Nicolson, Messrs Blumenthal, Fernandez, and Bedwell, and Mss Hamburger and Lenane), and Biometry Branch, National Institute of Neurological Disorders and Stroke (Dr Jeffries), Bethesda, Md; and the Montreal Neurological Institute, McGill University, Montreal, Quebec (Drs Zijdenbos, Paus, and Evans).

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