Abnormalities of Brain Structure and Function in Schizophrenia: Implications for Aetiology and Pathophysiology

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Abstract
In vivo imaging and post-mortem neuropathology studies have detected a variety of abnormalities in brain function and structure in patients with schizophrenia. Current models of the neural mechanisms involved focus primarily on frontal and medial temporal lobe structures and their interconnections, because deficits in these systems are relatively prominent against a background of generalized cerebral dysfunction, and because individuals with acquired lesions in these areas show many of the symptoms characteristic of schizophrenia. Family and twin studies have demonstrated similar abnormalities in some of the unaffected biological relatives of schizophrenics, indicating that some of these neuropathological changes are mediated in part by genetic predisposition to the disorder. Further, obstetric complications are associated with an increased risk for phenotypic schizophrenia and with greater severity of its neuropathological features in individuals at elevated genetic risk. These latter findings, combined with evidence of heterotopic displacement of neurones in temporolimbic and frontal regions and evidence that cognitive dysfunction during childhood precedes schizophrenia, imply that at least some of these brain abnormalities are neuro-developmental in origin. The view emerging from this work is that schizophrenia is a brain disease the neuropathological features of which result at least in part from the unique and interacting influences of genetic factors and adverse obstetric events in utero.