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OBJECTIVE: Structural and functional studies implicate multiple brain lesions as a basis for a functional dysconnectivity underlying the cognitive and symptom profiles in schizophrenia. The aim of this study was to examine the hypothesis that early-onset schizophrenia is associated with structural abnormalities in the prefrontal cortex, thalamus, and cerebellum, compatible with a dysconnectivity syndrome. METHOD: Two magnetic resonance imaging scans of 16 patients and 16 normal comparison subjects were undertaken on average 2 to 3 years apart. The participants were all from a defined geographic area in the United Kingdom with a population of 2.5 million. RESULTS: In comparison to the normal adolescents, the schizophrenic subjects demonstrated low prefrontal cortex and thalamic volumes. The relatively large difference in prefrontal and thalamic volumes in these adolescents with schizophrenia implies a more severe disease process than in adult subjects. CONCLUSIONS: The thalamic and frontal lobe findings provide preliminary, supportive structural evidence for a neurodevelopmental basis for a dysconnectivity syndrome, although the cerebellar findings were inconclusive.