A single-nucleotide polymorphism influences brain morphology in drug-näve patients with major depressive disorder

Asuka Katsuki, Shingo Kakeda, Keita Watanabe, Ryohei Igata, Yuka Otsuka, Taro Kishi, Le Hoa Nguyen, Issei Ueda, Nakao Iwata, Yukunori Korogi, Reiji Yoshimura

Research output: Contribution to journalArticle

Abstract

Objective: Recently, a genome-wide association study successfully identified genetic variants associated with major depressive disorder (MDD). The study identified 17 independent single-nucleotide polymorphisms (SNPs) significantly associated with diagnosis of MDD. These SNPs were predicted to be enriched in genes that are expressed in the central nervous system and function in transcriptional regulation associated with neurodevelopment. The study aimed to investigate associations between 17 SNPs and brain morphometry using magnetic resonance imaging (MRI) in drug-näve patients with MDD and healthy controls (HCs). Methods: Forty-seven patients with MDD and 42 HCs were included. All participants underwent T1-weighted structural MRI and genotyping. The genotype-diagnosis interactions associated with regional cortical thicknesses were evaluated using voxel-based morphometry for the 17 SNPs. Results: Regarding rs301806, an SNP in the RERE genomic regions, we found a significant difference in a genotype effect in the right-lateral orbitofrontal and postcentral lobes between diagnosis groups. After testing every possible diagnostic comparison, the genotype-diagnosis interaction in these areas revealed that the cortical thickness reductions in the MDD group relative to those in the HC group were significantly larger in T/T individuals than in C-carrier ones. For the other SNPs, no brain area was noted where a genotype effect significantly differed between the two groups. Conclusions: We found that a RERE gene SNP was associated with cortical thickness reductions in the right-lateral orbitofrontal and postcentral lobes in drug-näve patients with MDD. The effects of RERE gene polymorphism and gene-environment interactions may exist in brain structures of patients with MDD.

Original languageEnglish
Pages (from-to)2425-2432
Number of pages8
JournalNeuropsychiatric Disease and Treatment
Volume15
DOIs
Publication statusPublished - 01-01-2019

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Major Depressive Disorder
Single Nucleotide Polymorphism
Brain
Pharmaceutical Preparations
Genotype
Magnetic Resonance Imaging
Genes
Gene-Environment Interaction
Genome-Wide Association Study
Central Nervous System
Control Groups

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Katsuki, Asuka ; Kakeda, Shingo ; Watanabe, Keita ; Igata, Ryohei ; Otsuka, Yuka ; Kishi, Taro ; Nguyen, Le Hoa ; Ueda, Issei ; Iwata, Nakao ; Korogi, Yukunori ; Yoshimura, Reiji. / A single-nucleotide polymorphism influences brain morphology in drug-näve patients with major depressive disorder. In: Neuropsychiatric Disease and Treatment. 2019 ; Vol. 15. pp. 2425-2432.
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abstract = "Objective: Recently, a genome-wide association study successfully identified genetic variants associated with major depressive disorder (MDD). The study identified 17 independent single-nucleotide polymorphisms (SNPs) significantly associated with diagnosis of MDD. These SNPs were predicted to be enriched in genes that are expressed in the central nervous system and function in transcriptional regulation associated with neurodevelopment. The study aimed to investigate associations between 17 SNPs and brain morphometry using magnetic resonance imaging (MRI) in drug-n{\"a}ve patients with MDD and healthy controls (HCs). Methods: Forty-seven patients with MDD and 42 HCs were included. All participants underwent T1-weighted structural MRI and genotyping. The genotype-diagnosis interactions associated with regional cortical thicknesses were evaluated using voxel-based morphometry for the 17 SNPs. Results: Regarding rs301806, an SNP in the RERE genomic regions, we found a significant difference in a genotype effect in the right-lateral orbitofrontal and postcentral lobes between diagnosis groups. After testing every possible diagnostic comparison, the genotype-diagnosis interaction in these areas revealed that the cortical thickness reductions in the MDD group relative to those in the HC group were significantly larger in T/T individuals than in C-carrier ones. For the other SNPs, no brain area was noted where a genotype effect significantly differed between the two groups. Conclusions: We found that a RERE gene SNP was associated with cortical thickness reductions in the right-lateral orbitofrontal and postcentral lobes in drug-n{\"a}ve patients with MDD. The effects of RERE gene polymorphism and gene-environment interactions may exist in brain structures of patients with MDD.",
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Katsuki, A, Kakeda, S, Watanabe, K, Igata, R, Otsuka, Y, Kishi, T, Nguyen, LH, Ueda, I, Iwata, N, Korogi, Y & Yoshimura, R 2019, 'A single-nucleotide polymorphism influences brain morphology in drug-näve patients with major depressive disorder', Neuropsychiatric Disease and Treatment, vol. 15, pp. 2425-2432. https://doi.org/10.2147/NDT.S204461

A single-nucleotide polymorphism influences brain morphology in drug-näve patients with major depressive disorder. / Katsuki, Asuka; Kakeda, Shingo; Watanabe, Keita; Igata, Ryohei; Otsuka, Yuka; Kishi, Taro; Nguyen, Le Hoa; Ueda, Issei; Iwata, Nakao; Korogi, Yukunori; Yoshimura, Reiji.

In: Neuropsychiatric Disease and Treatment, Vol. 15, 01.01.2019, p. 2425-2432.

Research output: Contribution to journalArticle

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T1 - A single-nucleotide polymorphism influences brain morphology in drug-näve patients with major depressive disorder

AU - Katsuki, Asuka

AU - Kakeda, Shingo

AU - Watanabe, Keita

AU - Igata, Ryohei

AU - Otsuka, Yuka

AU - Kishi, Taro

AU - Nguyen, Le Hoa

AU - Ueda, Issei

AU - Iwata, Nakao

AU - Korogi, Yukunori

AU - Yoshimura, Reiji

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: Recently, a genome-wide association study successfully identified genetic variants associated with major depressive disorder (MDD). The study identified 17 independent single-nucleotide polymorphisms (SNPs) significantly associated with diagnosis of MDD. These SNPs were predicted to be enriched in genes that are expressed in the central nervous system and function in transcriptional regulation associated with neurodevelopment. The study aimed to investigate associations between 17 SNPs and brain morphometry using magnetic resonance imaging (MRI) in drug-näve patients with MDD and healthy controls (HCs). Methods: Forty-seven patients with MDD and 42 HCs were included. All participants underwent T1-weighted structural MRI and genotyping. The genotype-diagnosis interactions associated with regional cortical thicknesses were evaluated using voxel-based morphometry for the 17 SNPs. Results: Regarding rs301806, an SNP in the RERE genomic regions, we found a significant difference in a genotype effect in the right-lateral orbitofrontal and postcentral lobes between diagnosis groups. After testing every possible diagnostic comparison, the genotype-diagnosis interaction in these areas revealed that the cortical thickness reductions in the MDD group relative to those in the HC group were significantly larger in T/T individuals than in C-carrier ones. For the other SNPs, no brain area was noted where a genotype effect significantly differed between the two groups. Conclusions: We found that a RERE gene SNP was associated with cortical thickness reductions in the right-lateral orbitofrontal and postcentral lobes in drug-näve patients with MDD. The effects of RERE gene polymorphism and gene-environment interactions may exist in brain structures of patients with MDD.

AB - Objective: Recently, a genome-wide association study successfully identified genetic variants associated with major depressive disorder (MDD). The study identified 17 independent single-nucleotide polymorphisms (SNPs) significantly associated with diagnosis of MDD. These SNPs were predicted to be enriched in genes that are expressed in the central nervous system and function in transcriptional regulation associated with neurodevelopment. The study aimed to investigate associations between 17 SNPs and brain morphometry using magnetic resonance imaging (MRI) in drug-näve patients with MDD and healthy controls (HCs). Methods: Forty-seven patients with MDD and 42 HCs were included. All participants underwent T1-weighted structural MRI and genotyping. The genotype-diagnosis interactions associated with regional cortical thicknesses were evaluated using voxel-based morphometry for the 17 SNPs. Results: Regarding rs301806, an SNP in the RERE genomic regions, we found a significant difference in a genotype effect in the right-lateral orbitofrontal and postcentral lobes between diagnosis groups. After testing every possible diagnostic comparison, the genotype-diagnosis interaction in these areas revealed that the cortical thickness reductions in the MDD group relative to those in the HC group were significantly larger in T/T individuals than in C-carrier ones. For the other SNPs, no brain area was noted where a genotype effect significantly differed between the two groups. Conclusions: We found that a RERE gene SNP was associated with cortical thickness reductions in the right-lateral orbitofrontal and postcentral lobes in drug-näve patients with MDD. The effects of RERE gene polymorphism and gene-environment interactions may exist in brain structures of patients with MDD.

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