From syndrome to illness: delineating the pathophysiology of schizophrenia with PET

The Section on Clinical Brain Imaging of the Laboratory of Cerebral Metabolism has been engaged in studying regional brain metabolism by positron emission tomography (PET) to establish the pathophysiology of schizophrenia. Recent studies have revealed that the fluorodeoxyglucose (FDG) PET methodology can be applied successfully to determine the anatomical substrata of directed attention. In normal controls, the metabolic rate in the middle prefrontal cortex, measured during the ongoing performance of auditory discrimination, is associated with their accuracy of performance. In unmedicated patients with schizophrenia, even those who performed as well as normals, the metabolic rate in the mid-prefrontal cortex was found to be significantly lower than normal. Further, this decreased metabolic rate was unrelated to performance. In medicated patients with schizophrenia, at least part of the metabolic deficit remains, but this deficit appears to be performance-related. These findings suggest several conclusions. The mid-prefrontal cortex and its dopamine neurotransmitter pathway input are important biological determinants of sustained attention. Two types of prefrontal metabolic deficits may contribute to dysfunctional goal-directed behavior and, more speculatively, vulnerability to psychosis in some patients with schizophrenia. One deficit is sensitive to neuroleptics, and thus presumably to a change in the balance of regional brain dopamine input. A second deficit is unaffected by neurolpetic treatment.