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Su Lui, MD, PhD; Tao Li, MD, PhD; Wei Deng, MD, PhD; Lijun Jiang, MM; Qizhu Wu, PhD; Hehan Tang, MM; Qiang Yue, MD; Xiaoqi Huang, MD, PhD; Raymond C. Chan, PhD; David A. Collier, PhD; Shashwath A. Meda, MS; Godfrey Pearlson, MD; Andrea Mechelli, PhD; John A. Sweeney, PhD; Qiyong Gong, MD, PhD

Arch Gen Psychiatry. 2010;67(8):783-792. doi:10.1001/archgenpsychiatry.2010.84

Context  Most of what we know about antipsychotic drug effects is at the receptor level, distal from the neural system effects that mediate their clinical efficacy. Studying cerebral function in antipsychotic-naive patients with schizophrenia before and after pharmacotherapy can enhance understanding of the therapeutic mechanisms of these clinically effective treatments.

Objective  To examine alterations of regional and neural network function in antipsychotic-naive patients with first-episode schizophrenia before and after treatment with second-generation antipsychotic medication.

Design  Case-control study.

Setting  Huaxi MR Research Center and Mental Health Centre of the West China Hospital.

Participants  Thirty-four antipsychotic-naive patients with first-episode schizophrenia were scanned using gradient-echo echo-planar imaging while in a resting state. After 6 weeks of antipsychotic treatment, patients were rescanned. Thirty-four matched healthy control subjects were studied at baseline for comparison purposes.

Main Outcome Measures  The amplitude of low-frequency fluctuations (ALFF) of blood oxygen level–dependent signals, believed to reflect spontaneous neural activity, was used to characterize regional cerebral function. Functional connectivity across brain regions was evaluated using a seed voxel correlation approach and an independent component analysis. Changes in these measures after treatment were examined to characterize effects of antipsychotic drugs on regional function and functional integration.

Results  After short-term treatment with second-generation antipsychotic medications, patients showed increased ALFF, particularly in the bilateral prefrontal and parietal cortex, left superior temporal cortex, and right caudate nucleus. Increased regional ALFF was associated with a reduction of clinical symptoms, and a widespread attenuation in functional connectivity was observed that was correlated with increased regional ALFF.

Conclusions  We demonstrate for the first time, to our knowledge, that widespread increased regional synchronous neural activity occurs after antipsychotic therapy, accompanied by decreased integration of function across widely distributed neural networks. These findings contribute to the understanding of the complex systems-level effects of antipsychotic drugs.

Author Affiliations: Huaxi MR Research Center, Department of Radiology (Drs Lui, Wu, Tang, Yue, Huang, and Gong), and Department of Psychiatry and Psychiatric Laboratory (Drs Li, Deng, and Jiang), State Key Lab of Biotherapy, West China Hospital of Sichuan University, Chengdu, and Neuropsychology and Applied Cognitive Neuroscience Laboratory, Institute of Psychology, Chinese Academy of Sciences, Beijing (Prof Chan); Center for Cognitive Medicine, University of Illinois at Chicago, Chicago (Prof Sweeney); Olin Neuropsychiatry Research Center, Institute of Living, Hartford (Mr Meda and Prof Pearlson), and Department of Psychiatry, Yale University School of Medicine, New Haven (Prof Pearlson), Connecticut; and Section of Neuroimaging, Division of Psychological Medicine, Institute of Psychiatry King's College London, London, England (Drs Li and Mechelli and Prof Collier).

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