Abstract
BackgroundThe 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.MethodsEighty-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.ResultsFA 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.ConclusionsWe 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.
Highlights
Major depressive disorder (MDD) is one of the leading causes of disability and poses a great socioeconomic burden worldwide [1, 2]
We found that major depressive disorder (MDD) patients with the A allele showed reduced fractional anisotropy (FA) values for the left parahippocampal cingulum (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
Summary
Major depressive disorder (MDD) is one of the leading causes of disability and poses a great socioeconomic burden worldwide [1, 2]. The gene-by-environment interaction is known to lead to biochemical disturbance, dysfunctional neural networks, and structural alteration of the brain in MDD patients [5]. Recent developments in techniques of neuroimaging analysis have encouraged novel methodological approaches using structural changes in the brain as an endophenotype in genetic studies of MDD [6]. Numerous studies have found that several candidate genetic polymorphisms, including serotonin transporterlined polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF) Val66Met, tryptophan hydroxylase-2 (TPH-2), catechol-o-methyltransferase (COMT) Val158Met, serotonin receptor 1A gene (HTR1A), and monoamine oxidase A gene (MAOA) modulate morphologic brain changes in MDD patients [6, 7]. The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). 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
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