Extensive White Matter Abnormalities and Clinical Symptoms in Drug-Naive Patients With First-Episode Schizophrenia: A Voxel-Based Diffusion Tensor Imaging Study

Background: Increasing evidence shows that disruption of connectivity has been implicated as a central abnormality in schizophrenia, and the alterations in white matter may be the core basis for this disconnection. Diffusion tensor imaging (DTI) has shown white matter abnormalities in first-episode schizophrenia. However, few studies have examined the correlation between clinical symptoms and white matter abnormalities in drug-naive patients with first-episode schizophrenia.

Method: The white matter fractional anisotropy (FA) values of the whole-brain were determined by using voxel-based DTI in 39 drug-naive patients with first-episode schizophrenia (diagnosed according to DSM-IV) and 30 healthy controls matched for age and gender. The psychopathology of schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). The study was conducted from April 2009 to March 2010.

Results: The patients showed widespread FA reduction in several brain regions, including corpus callosum, brainstem, internal capsule, cingulate, and cerebellum in patients with first-episode schizophrenia when compared to healthy controls (all P values < .01 after adjusting for gender, age, and education). The correlation analysis showed a significant negative correlation between the FA value in the left cerebellum and positive symptoms (r38 = −0.32, P < .05) and a significant positive correlation between the FA values in the corpus callosum and both the PANSS general psychopathology subscore (r38 = 0.39, P < .01) and the PANSS total score (r38 = 0.33, P < .05).

Conclusions: Our results indicate that widespread disruption of white matter integrity occurs in an early stage of schizophrenic onset, suggesting an important role in pathogenesis and symptomatology of schizophrenia.