Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging

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J Psychiatry Neurosci 2017;42(3):150-163

Jing Jiang, MM;* You-Jin Zhao, MM;* Xin-Yu Hu, MD; Ming-Ying Du, MD; Zi-Qi Chen, MD; Min Wu, PhD; Kai-Ming Li, PhD; Hong-Yan Zhu, MD; Poornima Kumar, PhD; Qi-Yong Gong, MD, PhD

Abstract

Background: Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects.

Methods: We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size–signed differential mapping (AES-SDM). We used DTI query software for fibre tracking.

Results: Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle.

Limitations: The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data.

Conclusion: By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD.


*These authors contributed equally to this work.

Submitted Oct. 28, 2015; Revised Feb. 23, 2016; Revised Apr. 29, 2016; Revised July 7, 2016; Accepted July 12, 2016; Early-released Oct. 25, 2016

Acknowledgements: The authors thank all authors of the included studies and especially thank Dr. Joaquim Radua for his kind help and suggestions in using TBSS template of AES-SDM to combine VBA and TBSS studies in our meta-analysis. This study was supported by the National Natural Science Foundation (Grant Nos. 81000605, 81220108013 and 0040205401A59). Q. Gong also acknowledges his Visiting Professor appointment in the Department of Psychiatry at the Yale School of Medicine, Yale University, USA.

Affiliations: From the Huaxi MR Research Center (HMRRC), Department of Radiology, Psychoradiology and Psychiatry, West China Hospital and Schools of Clinical Medicine, Sichuan University, Chengdu, China (Jiang, Zhao, Hu, Du, Chen, Wu, Li, Zhu, Gong); the Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China (Zhu); the Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Mass., USA (Kumar); Department of Psychiatry, Harvard Medical School, Boston, Mass., USA (Kumar); the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn., USA (Gong).

Competing interests: None declared.

Contributors: J. Jiang, Y.-J. Zhao, K.-M. Li, H.-Y. Zhu, P. Kumar and Q.-Y. Gong designed the study. X.-Y. Hu, M.-Y. Du, Z.-Q. Chen and M. Wu acquired the data, which J. Jiang and Y.-J. Zhao analyzed. J. Jiang, Y.-J. Zhao, K.-M. Li and P. Kumar wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.150341

Correspondence to: H. Zhu or Q. Gong, Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, 610041, China; hyzhu_hmrrc@126.com or qiyonggong@hmrrc.org.cn