Mesolimbic Activity Associated with Psychosis in Schizophrenia. Symptom-specific PET Studies

Hallucinations and paranoid delusions are prominent among the positive symptoms of schizophrenia. Such psychotic symptoms are notable for their aberrant representations of, and relation to, the external world and for the emotional/motivational valence associated with the representations. As mesolimbic structures, including the amygdala and ventral striatum, are thought to play a significant role in imparting emotional valence to external stimuli, we here examine the mesolimbic findings of H215O PET studies designed to probe the functional neuroanatomy of psychosis. Patients with schizophrenia (including those with active hallucinations, those with active paranoid delusions, and those without active positive symptoms at the time of scanning) and healthy control subjects were studied. An event-related PET paradigm was used to identify the neural correlates of hallucinations, and a modified emotional stroop paradigm (with threat versus neutral words) was used to test the hypothesis that paranoid patients would have increased mesolimbic activity in response to threat, and even in response to neutral stimuli. The findings suggest that the positive psychotic symptoms of hallucinations and delusions share similar functional neuroanatomical features of increased mesotemporal and ventral striatal activity in the setting of decreased prefrontal activity. The pattern is evident even in a neutral context, unlike the case for normal subjects, who show such features only in response to threat. The implications of these findings for a pathophysiology of psychosis will be discussed in the context of the behavioral neuroanatomical literature in animals and humans.