Background: Previous research has provided evidence for brain abnormalities in schizophrenia, but their relationship to specific clinical symptoms and syndromes remains unclear.

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These data, while preliminary, suggest that impaired white matter integrity in the inferior frontal region may be associated with the severity of negative symptoms in schizophrenia.

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The effects of d-amphetamine (0.5 mg/kg PO) on regional cerebral glucose utilization were measured with Positron Emission Tomography (PET). Subjects included ten chronic schizophrenics and six controls who received amphetamine, and six chronic schizophrenics and nine controls who received placebo or no treatment. Amphetamine decreased glucose metabolism in all regions studied (frontal, temporal, and striatal) in normal and schizophrenic subjects. The metabolic effects of amphetamine were correlated with plasma level of the drug. Cortical atrophy was associated with a blunted metabolic response.

The purpose of this study was to assess further the effect of amphetamine on negative symptoms of schizophrenia. Thirty-seven schizophrenic males meeting DSM-III criteria were rated with the Brief Psychiatric Rating Scale, the Abrams and Taylor Scale, and the Abnormal Involuntary Movements Scale before and after double-blind administration of either amphetamine (n = 26) or placebo (n = 11). Our results indicated that amphetamine administration generally did not improve negative symptoms, even when accounting for changes in positive symptoms. However, greater baseline negative symptoms were associated with a modest diminution after amphetamine treatment. Therefore, amphetamine may modestly improve negative symptoms in those schizophrenics in whom this symptomatology is more severe.