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

Abstract

With genetic and neurochemical findings pointing to a biological aetiology, considerable effort has been devoted to finding direct evidence of brain abnormality in schizophrenia. CT, MRI, post-mortem and functional imaging studies are reviewed to assess which structural and/or functional brain abnormalities have been consistently demonstrated. 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 post-mortem studies, but the most promising findings concern temporal lobe 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. 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.