Psychological Medicine

Original Articles

A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia

V. Cheunga1, C. Cheunga1, G. M. McAlonana1a2, Y. Denga1, J. G. Wonga1, L. Yipa3, K. S. Taia3, P. L. Khonga2a3, P. Shama1a2 and S. E. Chuaa1a2 c1

a1 Department of Psychiatry, The University of Hong Kong, Pokfulam, S.A.R. China

a2 State Key Laboratory for Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, S.A.R. China

a3 Department of Radiology, Queen Mary Hospital, Pokfulam, S.A.R. China


Background Diffusion tensor imaging (DTI) can be used to investigate cerebral structural connectivity in never-medicated individuals with first-episode schizophrenia.

Method Subjects with first-episode schizophrenia according to DSM-IV-R who had never been exposed to antipsychotic medication (n=25) and healthy controls (n=26) were recruited. Groups were matched for age, gender, best parental socio-economic status and ethnicity. All subjects underwent DTI and structural magnetic resonance imaging (MRI) scans. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values differed significantly between groups. A confirmatory region-of-interest (ROI) analysis of FA scores was performed in which regions were placed blind to group membership.

Results In patients, FA values significantly lower than those in healthy controls were located in the left fronto-occipital fasciculus, left inferior longitudinal fasciculus, white matter adjacent to right precuneus, splenium of corpus callosum, right posterior limb of internal capsule, white matter adjacent to right substantia nigra, and left cerebral peduncle. ROI analysis of the corpus callosum confirmed that the patient group had significantly lower mean FA values than the controls in the splenium but not in the genu. The intra-class correlation coefficient (ICC) for independent ROI measurements was 0.90 (genu) and 0.90 (splenium). There were no regions where FA values were significantly higher in the patients than in the healthy controls.

Conclusions Widespread structural dysconnectivity, including the subcortical region, is already present in neuroleptic-naive patients in their first episode of illness.

(Received April 20 2007)

(Revised July 26 2007)

(Accepted August 14 2007)

(Online publication October 22 2007)


c1 Address for correspondence: Dr Siew-eng Chua, Department of Psychiatry Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong. (Email: