Effects of a Polymorphism of the Neuronal Amino Acid Transporter SLC6A15 Gene on Structural Integrity of White Matter Tracts in Major Depressive Disorder

• Published in: PLOS ONE Vol. 11; no. 10; p. e0164301
• Main Authors: Choi, Sunyoung, Han, Kyu-Man, Kang, June, Won, Eunsoo, Chang, Hun Soo, Tae, Woo Suk, Son, Kyu Ri, Kim, Su-Jin, Lee, Min-Soo, Ham, Byung-Joo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science (PLoS) 10.10.2016; Public Library of Science
• Subjects: Adult; Alleles; Amino Acid Transport Systems, Neutral; Amino Acid Transport Systems, Neutral - genetics; Amino acids; Anisotropy; Biology and Life Sciences; Bipolar disorder; Brain; Brain research; Brain-derived neurotrophic factor; Cingulum; Corpus callosum; Depressive Disorder, Major; Depressive Disorder, Major - diagnostic imaging; Depressive Disorder, Major - enzymology; Diffusion; Diffusion Tensor Imaging; Female; Fornix; Gene polymorphism; Genes; Genetic aspects; Genetic polymorphisms; Genotypes; Glutamate; Homozygotes; Hospitals; Humans; Magnetic resonance; Magnetic resonance imaging; Major depressive disorder; Male; Medical imaging; Medicine; Medicine and Health Sciences; Mental depression; Middle Aged; Nerve Tissue Proteins; Nerve Tissue Proteins - genetics; Neural circuitry; Neural networks; Neuroimaging; Neurons; NMR; Nuclear magnetic resonance; Parahippocampal gyrus; Patients; Physical Sciences; Polymorphism; Polymorphism, Genetic; Psychiatry; Q; R; Research and Analysis Methods; Research Article; Science; Serotonin; Social Sciences; Stress; Structural integrity; Studies; Substantia alba; Transporter; Values; White Matter; White Matter - diagnostic imaging; White Matter - enzymology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0164301

The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). It is presumed to be involved in the pathophysiology of MDD through regulation of glutamate transmission in the brain. However, the involvement of this gene in microstructural changes in white matter (WM) tracts remains unclear. We aimed to investigate the influence of a polymorphism of this gene (rs1545853) on the structural integrity of WM tracts in the cortico-limbic network. Eighty-six patients with MDD and 64 healthy controls underwent T1-weighted structural magnetic resonance imaging, including diffusion tensor imaging (DTI), and genotype analysis. We selected the genu of the corpus callosum, the uncinate fasciculus, cingulum, and fornix as regions of interest, and extracted fractional anisotropy (FA) values using the FMRIB Diffusion Toolbox software. FA values for the left parahippocampal cingulum (PHC) was significantly reduced in the patients with MDD compared to healthy control participants (p = 0.004). We also found that MDD patients with the A allele showed reduced FA values for the left PHC than did healthy controls with the A allele (p = 0.012). There was no significant difference in the FA value of left PHC for the comparison between the G homozygotes of MDD and healthy control group. We observed an association between the risk allele of the SLC6A15 gene rs1545843 and the WM integrity of the PHC in MDD patients, which is known to play an important role in the neural circuit involved in emotion processing.