A PET study of the pathophysiology of negative symptoms in schizophrenia

Objective: Positron emission tomography (PET) was used to compare cerebral metabolic patterns in schizophrenic subjects with predominantly negative symptoms (alogia, affective flattening, avolition, and attentional impairment) and in those with predominantly positive symptoms. Method: Fourteen right-handed male subjects with DSM-IV schizophrenia were assigned to groups with predominantly negative or predominantly positive symptoms on the basis of their post-drug-washout scores on the Positive and Negative Syndrome Scale. The patients were compared to seven age- and gender-matched normal volunteers. PET scans with [F-18]fluorodeoxyglucose were obtained during a degraded Continuous Performance Task to measure absolute glucose metabolic rates. Statistical parametric mapping was used to estimate the regional metabolic differences between groups. Results: The subjects with predominantly negative symptoms had significant differences in glucose metabolic rates, compared to both the subjects with predominantly positive symptoms and the normal subjects. Negative symptom subjects had a lower glucose metabolic rate in the right hemisphere, especially in the temporal and ventral prefrontal cortices, compared to the other groups, and higher metabolic rates in the cerebellar cortex and in the lower deep cerebellar nuclei. Negative symptom subscale scores were negatively correlated with glucose metabolic rates for most of the brain areas that differentiated subjects with predominantly negative symptoms from those with predominantly positive symptoms. Conclusions: Schizophrenic subjects with predominantly negative symptoms have greater metabolic abnormalities than subjects with predominantly positive symptoms, particularly in frontal, temporal, and cerebellar circuitry. These results are consistent with abnormalities in corticocortical, corticobasal ganglia, mesocortical dopamine, and cerebellar-thalamic-prefrontal circuits, which may underlie the negative symptoms of schizophrenia.