Hypofrontality in schizophrenia: distributed dysfunctional circuits in neuroleptic-naïve patients

• Published in: The Lancet (British edition) Vol. 349; no. 9067; pp. 1730 - 1734
• Main Authors: Andreasen, Nancy C, O'Leary, Daniel S, Flaum, Michael, Nopoulos, Peg, Watkins, G Leonard, Ponto, Laura L Boles, Hichwa, Richard D
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 14.06.1997; Lancet; Elsevier Limited
• Subjects: Adult; Adult and adolescent clinical studies; Biological and medical sciences; Brain; Brain - blood supply; Brain - diagnostic imaging; Brain - metabolism; Cerebrovascular Circulation - physiology; Cognitive ability; Female; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Mental disorders; Neurology; Prefrontal Cortex - blood supply; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - physiopathology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - diagnostic imaging; Schizophrenia - metabolism; Schizophrenia - physiopathology; Schizophrenic Psychology; Statistical methods; Tomography, Emission-Computed; Human; Evaluation; Nervous system diseases; Cerebral cortex; Radiodiagnosis; Positron emitter; Schizophrenia; Anatomy; Blood flow; Vascular disease; Frontal; Medical imagery; Computerized axial tomography; Psychopathology; Diagnostic aid; Localization; Comparative study; Brain (vertebrata)
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(96)08258-X

There have been reports that patients with schizophrenia have decreased metabolic activity in prefrontal cortex. However, findings have been confounded by medication effects, chronic illness, and difficulties of measurement. We aimed to address these problems by examination of cerebral blood flow with positron emission tomography (PET). We studied 17 neuroleptic-naïve patients at the early stages of illness by means of image analysis and statistical methods that can detect abnormalities at the gyral level. An initial omnibus test with a randomisation analysis indicated that patients differed from 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 perfusion were also identified (eg, thalamus, cerebellum, retrosplenial cingulate), which suggests an imbalance in distributed cortical and subcortical circuits. These distributed dysfunctional circuits may form the neural basis of schizophrenia through cognitive impairment of the brain, which prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as hallucinations, delusions, and loss of volition.