Longitudinal study of brain morphology in first episode schizophrenia

Background: Beginning with Kraepelin, schizophrenia has been viewed as a pr ogressive disorder. Although numerous studies of the longitudinal course of schizophrenia have demonstrated the clinical deterioration that occurs pre dominantly in the early stages of the illness, the pathophysiology of this clinical phenomenon has not been established. This aspect of the illness ma y be of critical importance to understanding the pathogenesis of schizophre nia and determining preventive therapeutic strategies. Abnormalities in bra in morphology have been consistently described in schizophrenia but it is n ot known when in the natural history of the illness they arise and whether they are progressive. Previous studies of brain morphology have been inconc lusive, in part because of the variability of methods far image acquisition and analysis, assessment of patients already at chronic stages of their il lness with extensive prior treatment exposure, and inadequate periods of fo llow-up, Methods: To address these questions we examined 107 patients in their first episode of schizophrenia or schizoaffective disorder and 20 healthy volunt eers using high resolution magnetic resonance imaging (MRI) and clinical as sessments of psychopathology and treatment outcome for periods of up to 6 y ears. Fifty-one patients and 13 control subjects had MRIs after at least 12 months of follow-up, Results: Results confirm the findings of ventricular enlargement and anteri or hippocampal volume reductions in first episode schizophrenia patients th at have been previously reported, In addition, we found changes in selected structures over time in relation to treatment outcome, including increases in ventricular volume that were associated with poor outcome patients, Con trary to our hypothesis, there were no significant reductions in cortical a nd hippocampal volumes over time. Conclusions: The finding of progressive ventricular enlargement in patients with poor outcome schizophrenia is consistent with the hypothesis that per sistent positive and negative symptoms result in progressive brain changes in the form of ventricular enlargement, possibly due to neurodegeneration r ather than the confounding effects of treatment. Future studies of first ep isodes of schizophrenia should utilize higher resolution imaging techniques that compare clinically well characterized patients with and without poor outcome and recurrent symptoms to control subjects who are well matched to patients for age and gender. There is also a need to control for treatment effects of typical antipsychotic medication on brain structure. Biol Psychi atry 2001;49:487-499 (C) 2001 Society of Biological Psychiatry.