Schizophrenia - A brain disease? A critical review of structural and functional cerebral abnormality in the disorder

Abstract

Background. With genetic and neurochemical findings pointing to a biological aetiology, considerable effort has been devoted to finding direct evidence of brain abnormality in schizophrenia. Method. CT, MRI, post-mortem and functional imaging studies are reviewed to assess which structural and/or functional brain abnormalities have been consistently demonstrated. Results. The only well-established structural abnormality in schizophrenia is lateral ventricular enlargement; this is modest and there is a large overlap with the normal population. There is no consensus on the presence of any localised structural abnormality from MRI and postmortem studies, but the most promising findings concern temporal robe limbic structures. Hypofrontality is not a well-replicated finding in schizophrenia under resting conditions, but the evidence is stronger for a selective association with negative symptoms. A number of studies have found hypofrontality under conditions of neuropsychological task activation. However, findings in these studies are divided and a recent methodologically sophisticated study has failed to confirm it, although this study suggested a decoupling of prefrontal and temporal function. Conclusion. Schizophrenia is characterised by minor structural abnormality which, in the case of lateral ventricular enlargement, may be better understood as a risk factor than a causative lesion. The functional imaging findings are not transparent but suggest that, as a disorder, schizophrenia shows complex alterations in regional patterns of activity rather than any simple deficit in prefrontal function.