Psychological Medicine

Original Articles

White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment

Q. Wanga1a2, C. Cheunga3, W. Denga1a2, M. Lia1, C. Huanga1, X. Maa1a2, Y. Wanga1a2, L. Jianga1, P. C. Shama3, D. A. Colliera4, Q. Gonga5, S. E. Chuaa3, G. M. McAlonana6 c1 and T. Lia1a2 c1

a1 Mental Health Centre and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China

a2 State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China

a3 Department of Psychiatry, University of Hong Kong, Pokfulam, SAR China

a4 MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK

a5 Huaxi MR Research Centre, Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

a6 Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College London, UK


Background It is not clear whether the progressive changes in brain microstructural deficits documented in previous longitudinal magnetic resonance imaging (MRI) studies might be due to the disease process or to other factors such as medication. It is important to explore the longitudinal alterations in white-matter (WM) microstructure in antipsychotic-naive patients with first-episode schizophrenia during the very early phase of treatment when relatively ‘free’ from chronicity.

Method Thirty-five patients with first-episode schizophrenia and 22 healthy volunteers were recruited. High-resolution diffusion tensor imaging (DTI) was obtained from participants at baseline and after 6 weeks of treatment. A ‘difference map’ for each individual was calculated from the 6-week follow-up fractional anisotropy (FA) of DTI minus the baseline FA. Differences in Positive and Negative Syndrome Scale (PANSS) scores and Global Assessment of Functioning (GAF) scores between baseline and 6 weeks were also evaluated and expressed as a 6-week/baseline ratio.

Results Compared to healthy controls, there was a significant decrease in absolute FA of WM around the bilateral anterior cingulate gyrus and the right anterior corona radiata of the frontal lobe in first-episode drug-naive patients with schizophrenia following 6 weeks of treatment. Clinical symptoms improved during this period but the change in FA did not correlate with the changes in clinical symptoms or the dose of antipsychotic medication.

Conclusions During the early phase of treatment, there is an acute reduction in WM FA that may be due to the effects of antipsychotic medications. However, it is not possible to entirely exclude the effects of underlying progression of illness.

(Received February 24 2012)

(Revised November 06 2012)

(Accepted January 24 2013)

(Online publication February 27 2013)

Key words

  • First episode;
  • longitudinal study;
  • microstructural deficits;
  • schizophrenia