Effects of a Polymorphism of the Neuronal Amino Acid Transporter SLC6A15 Gene on Structural Integrity of White Matter Tracts in Major Depressive Disorder
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...
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| Published in | PLOS ONE Vol. 11; no. 10; p. e0164301 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science (PLoS)
10.10.2016
Public Library of Science |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1932-6203 1932-6203 |
| DOI | 10.1371/journal.pone.0164301 |
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| Abstract | 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. |
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| AbstractList | 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. Background 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. Methods 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. Results 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. Conclusions 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. 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. 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. Background 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. Methods 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. Results 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. Conclusions 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. |
| Audience | Academic |
| Author | Min Soo Lee Kyu Man Han Kyu Ri Son Byung Joo Ham June Kang Sunyoung Choi Su Jin Kim Hun Soo Chang Woo Suk Tae Eunsoo Won |
| AuthorAffiliation | 4 Department of Medical Bioscience, Graduate school, Soonchunhyang University, Bucheon, South Korea 5 Brain Convergence Research Center, Korea University Anam Hospital, Seoul, South Korea 1 Department of Brain and Cognitive Engineering, Korea University, Seoul, Republic of Korea 2 Department of Psychiatry, Korea University College of Medicine, Seoul, Republic of Korea University of Texas Health Science Center at San Antonio Cancer Therapy and Research Center at Houston, UNITED STATES 6 Department of Radiology, Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea 7 Department of Emergency Medicine, College of Medicine, Korea University, Seoul, Republic of Korea 3 Department of Biomedical Sciences, Korea University College of Medicine, Seoul, South Korea |
| AuthorAffiliation_xml | – name: 2 Department of Psychiatry, Korea University College of Medicine, Seoul, Republic of Korea – name: 1 Department of Brain and Cognitive Engineering, Korea University, Seoul, Republic of Korea – name: 5 Brain Convergence Research Center, Korea University Anam Hospital, Seoul, South Korea – name: 6 Department of Radiology, Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea – name: 4 Department of Medical Bioscience, Graduate school, Soonchunhyang University, Bucheon, South Korea – name: 3 Department of Biomedical Sciences, Korea University College of Medicine, Seoul, South Korea – name: University of Texas Health Science Center at San Antonio Cancer Therapy and Research Center at Houston, UNITED STATES – name: 7 Department of Emergency Medicine, College of Medicine, Korea University, Seoul, Republic of Korea |
| Author_xml | – sequence: 1 givenname: Sunyoung surname: Choi fullname: Choi, Sunyoung – sequence: 2 givenname: Kyu-Man surname: Han fullname: Han, Kyu-Man – sequence: 3 givenname: June surname: Kang fullname: Kang, June – sequence: 4 givenname: Eunsoo surname: Won fullname: Won, Eunsoo – sequence: 5 givenname: Hun Soo surname: Chang fullname: Chang, Hun Soo – sequence: 6 givenname: Woo Suk surname: Tae fullname: Tae, Woo Suk – sequence: 7 givenname: Kyu Ri surname: Son fullname: Son, Kyu Ri – sequence: 8 givenname: Su-Jin surname: Kim fullname: Kim, Su-Jin – sequence: 9 givenname: Min-Soo surname: Lee fullname: Lee, Min-Soo – sequence: 10 givenname: Byung-Joo surname: Ham fullname: Ham, Byung-Joo |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceptualization: BJH. Formal analysis: SC KMH EW HSC. Funding acquisition: BJH. Investigation: SC KMH SJK. Methodology: SC KMH JK KRS WST. Resources: BJH. Supervision: BJH MSL. Visualization: SC KMH. Writing – original draft: SC KMH. Writing – review & editing: SC KMH. Competing Interests: There is no conflict of interest to declare. |
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| Snippet | 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... Background The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). It is presumed to be involved in the... BACKGROUNDThe SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). It is presumed to be involved in the... Background The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). It is presumed to be involved in the... |
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| SubjectTerms | 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 |
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| Title | Effects of a Polymorphism of the Neuronal Amino Acid Transporter SLC6A15 Gene on Structural Integrity of White Matter Tracts in Major Depressive Disorder |
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