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Extensive brain structural network abnormality in first-episode treatment-naive patients with schizophrenia: morphometrical and covariation study

  • Z. Chen (a1) (a2) (a3), W. Deng (a1) (a2), Q. Gong (a4), C. Huang (a1) (a2), L. Jiang (a1) (a2), M. Li (a1) (a2), Z. He (a1) (a2), Q. Wang (a1) (a2), X. Ma (a1) (a2), Y. Wang (a1) (a2), S. E. Chua (a5), G. M. McAlonan (a5), P. C. Sham (a5), D. A. Collier (a6), P. McGuire (a7) (a8) and T. Li (a1) (a2)...



Alterations in gray matter (GM) are commonly observed in schizophrenia. Accumulating studies suggest that the brain changes associated with schizophrenia are distributed rather than focal, involving interconnected networks of areas as opposed to single regions. In the current study we aimed to explore GM volume (GMV) changes in a relatively large sample of treatment-naive first-episode schizophrenia (FES) patients using optimized voxel-based morphometry (VBM) and covariation analysis.


High-resolution T1-weighted images were obtained using 3.0-T magnetic resonance imaging (MRI) from 86 first-episode drug-naive patients with schizophrenia and 86 age- and gender-matched healthy volunteers. Symptom severity was evaluated using the Positive and Negative Syndrome Scale (PANSS). GMV was assessed using optimized VBM and in 16 regions of interest (ROIs), selected on the basis of a previous meta-analysis. The relationships between GMVs in the ROIs were examined using an analysis of covariance (ANCOVA).


The VBM analysis revealed that first-episode patients showed reduced GMV in the hippocampus bilaterally. The ROI analysis identified reductions in GMV in the left inferior frontal gyrus, bilateral hippocampus and right thalamus. The ANCOVA revealed different patterns of regional GMV correlations in patients and controls, including of inter- and intra-insula, inter-amygdala and insula–postcentral gyrus connections.


Schizophrenia involves regional reductions in GMV and changes in GMV covariance in the insula, amygdala and postcentral gyrus. These findings were evident at the onset of the disorder, before treatment, and therefore cannot be attributable to the effects of chronic illness progression or medication.


Corresponding author

* Address for correspondence: Professor T. Li, M.D., Ph.D., Mental Health Center and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China. (Email:


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