HYPOFRONTALITY IN SCHIZOPHRENIA - DISTRIBUTED DYSFUNCTIONAL CIRCUITS IN NEUROLEPTIC-NAIVE PATIENTS

Background There have been reports that patients with schizophrenia ha ve decreased metabolic activity in prefrontal cortex. However, finding s have been confounded by medication effects, chronic illness, and dif ficulties of measurement. We aimed to address these problems by examin ation of cerebral blood flow with positron emission tomography (PET). Methods We studied 17 neuroleptic-native patients at the early stages of illness by means of image analysis and statistical methods that can detect abnormalities at the gyral level. Findings An initial omnibus test with a randomisation analysis indicated that patients differed fr om normal controls at the 0.06 level. In the follow-up analysis, three separate prefrontal regions had decreased perfusion (lateral, orbital , medial), as well as regions in inferior temporal and parietal cortex that are known to be anatomically connected. Regions with increased p erfusion were also identified (eg, thalamus, cerebellum, retrosplenial cingulate), which suggests an imbalance in distributed cortical and s ubcortical circuits. Interpretation These distributed dysfunctional ci rcuits may form the neural basis of schizophrenia through cognitive im pairment of the brain, which prevents it from processing input efficie ntly and producing output effectively, thereby leading to symptoms suc h as hallucinations, delusions, and loss of volition.