Roles of 5,10-Methylenetetrahydrofolate Reductase C677T Polymorphisms in First-Episode, Drug-Naive Adult Patients With Depression

Zhuoqing Li; Bo He; Jian Xu; Nan Dai; Liangliang Ping; Cong Zhou; Zonglin Shen; Xiufeng Xu; Yuqi Cheng

doi:10.3389/fpsyt.2020.531959

Roles of 5,10-Methylenetetrahydrofolate Reductase C677T Polymorphisms in First-Episode, Drug-Naive Adult Patients With Depression

Front Psychiatry. 2020 Dec 7:11:531959. doi: 10.3389/fpsyt.2020.531959. eCollection 2020.

Authors

Zhuoqing Li¹, Bo He², Jian Xu³, Nan Dai¹, Liangliang Ping⁴, Cong Zhou¹, Zonglin Shen¹, Xiufeng Xu¹, Yuqi Cheng¹

Affiliations

¹ Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.
² Department of Medical Imaging, First Affiliated Hospital of Kunming Medical University, Kunming, China.
³ Department of Internal Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, China.
⁴ Department of Psychiatry, Xianyue Hospital, Xiamen, China.

Abstract

5,10-Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is considered as a predisposition and promising genetic candidate to major depressive disorder (MDD), as it is associated with impaired one-carbon cycles, which may be involved in the pathogenesis of depression. Cortical thickness (CT) and subcortical structure volumes have been extensively studied in MDD and have been proposed as one of the phenotypes for MDD. We intend to discuss the association between CT, subcortical structure volume, and MTHFR C677T polymorphism in first-episode, treatment-naive patients with MDD. In this study, 127 adult patients with MDD and 101 age- and gender-matched healthy controls (HCs) were included. All subjects underwent T1-weighted MRI, MTHFR C677T genotyping, and FreeSurfer software-based morphological analysis. MDD patients have been detected to have significantly decreased volumes in the left nucleus accumbens (P < 0.001). The MTHFR 677 T allele carriers manifested with thinner CT in the left caudal anterior cingulate cortex (cACC, P = 0.009) compared with CC genotype. There were significant genotype-by-diagnosis interactions for the CT in the left cACC (P = 0.009), isthmus cingulate (P = 0.002), medial orbitofrontal lobe (P = 0.012), posterior cingulate (P = 0.030), and the right lateral orbitofrontal lobe (P = 0.012). We also found a trend in the interaction effect on the volume of the left putamen (P = 0.050). Our results revealed that MTHFR C677T polymorphism may be involved in the dysfunction of limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuits mediating emotion processing, which may contribute to pathogenesis of MDD.

Keywords: MTHFR C677T; anterior cingulate cortex; cortical thickness; major depressive disorder; subcortical structure volume.