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Genetic effects on white matter integrity in drug-naive patients with major depressive disorder: a diffusion tensor imaging study of 17 genetic loci associated with depressive symptoms

Authors Kakeda S, Watanabe K, Katsuki A, Sugimoto K, Ueda I, Igata N, Kishi T, Iwata N, Abe O, Yoshimura R, Korogi Y

Received 9 October 2018

Accepted for publication 10 January 2019

Published 29 January 2019 Volume 2019:15 Pages 375—383

DOI https://doi.org/10.2147/NDT.S190268

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Roger Pinder


Shingo Kakeda,1 Keita Watanabe,1 Asuka Katsuki,2 Koichiro Sugimoto,1 Issei Ueda,1 Natsuki Igata,1 Taro Kishi,3 Nakao Iwata,3 Osamu Abe,4 Reiji Yoshimura,2 Yukunori Korogi1

1Department of Radiology, University of Occupational and Environmental Health, Kitakyushu, Japan; 2Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Psychiatry, Fujita Health University, School of Medicine, Toyoake, Japan; 4Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Background: A genome-wide association study using megadata identified 17 single-nucleotide polymorphisms (SNPs) in candidate genes for major depressive disorder (MDD). These MDD susceptibility polymorphisms may affect white matter (WM) integrity. This study aimed to investigate the relationship between WM alterations and 17 SNPs in candidate genes for MDD in the first depressive episode of drug-naive MDD patients using a tract-based spatial statistics (TBSS) method.
Methods: Thirty-five drug-naive MDD patients with a first depressive episode and 47 age- and sex-matched healthy subjects underwent diffusion tensor imaging scans and genotyping. The genotype–diagnosis interactions related to WM integrity were evaluated using TBSS for the 17 SNPs.
Results: For the anterior thalamic radiation, cingulum, corticospinal tract, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, uncinate fasciculus, forceps major, and forceps minor, the genotype effect significantly differed between diagnosis groups (P<0.05, family-wise error corrected) in only one SNP, rs301806, in the arginine–glutamic acid dipeptide (RE) repeats (RERE) gene.
Conclusion: The RERE polymorphism was associated with WM alterations in first-episode and drug-naive MDD patients, which may be at least partially related to the manifestation of MDD. Future studies are needed to explore the gene–environment interactions with regard to individual WM integrity.

Keywords: depressive disorder, single-nucleotide polymorphism, MRI, fractional anisotropy, tract-based spatial statistics, arginine–glutamic acid dipeptide repeats gene

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