A Selective Review of Cerebral Abnormalities in Patients With First-Episode Schizophrenia Before and After Treatment

The question of whether there are significant changes in brain anatomy and function at illness onset and over the early course of schizophrenia is a crucial issue with broad implications for prognosis, patient care, and models of illness pathophysiology. Prefrontal hypoactivity and hippocampal and subcortical hyperactivity at the onset of illness may represent a core illness pathophysiology. Gray matter changes have been most robust within thalamo-cortical networks, whereas altered brain activity has been most pronounced in fronto-parietal and default-mode networks. These findings indicate that regional anatomical and functional brain abnormalities are significantly dissociated during the early course of schizophrenia prior to antipsychotic treatment. One possible explanation is that functional MRI may reflect physiological alterations related to acute psychosis or consequences of distal anatomic changes, while changes in brain anatomy reflect more stable and long-standing alterations. The relative stability of brain measures in the early years after illness onset stands in contrast to indirect evidence for moderate progressive changes provided by our recent study of chronic never-treated patients. Our recent cross-sectional study of never-treated patients with chronic schizophrenia found an accelerated age-related decline in cortical thickness, relative to healthy controls, that could not be attributed to medication effects. Studies must consider both the clinical heterogeneity that affects findings of brain changes within schizophrenia and the low specificity of the brain changes, which can occur in other early-onset mental disorders as well.