A Combined Study of SLC6A15 Gene Polymorphism and the Resting-State Functional Magnetic Resonance Imaging in First-Episode Drug-Naive Major Depressive Disorder

Sep 16, 2017Genetic testing and molecular biomarkers

SLC6A15 Gene Variations and Resting Brain Activity in First-Time Untreated Major Depression

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Abstract

MDD patients with A+ genotypes show decreased resting-state brain activity in the medial cingulum compared to those with the GG genotype.

The SLC6A15 gene polymorphism rs1545843 is associated with changes in brain activity in major depressive disorder (MDD) patients.
Normal controls with A+ genotypes exhibited increased brain activity in several regions, while MDD patients with A+ genotypes showed decreased activity in the medial cingulum.
Differences in brain activity were observed in the frontal, parietal, and temporal lobes related to disease status.
No interaction was found between the rs1545843 genotypes and disease status.
Increased activity in the left corpus callosum correlated positively with depression severity, while the right middle temporal gyrus showed a negative correlation with retardation.

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AIMS: The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). However, the mechanism underlying the effects of how the SLC6A15 gene affects functional brain activity of patients with MDD remains unknown.

METHODS: In the present study, we investigated the effect of the SLC6A15 gene polymorphism, rs1545843, on resting-state brain function in MDD with the imaging genomic technology and the regional homogeneity (ReHo) method. Sixty-seven MDD patients and 44 healthy controls underwent functional magnetic resonance imaging scans and genotyping. The differences in ReHo between genotypes were initially tested using the student's t test. We then performed a 2 × 2 (genotypes × disease status) analysis of variance to identify the main effects of genotypes, disease status, and their interactions in MDD.

RESULTS: MDD patients with A+ genotypes showed decreased ReHo in the medial cingulum compared with MDD patients with the GG genotype. This was in contrast to normal controls with A+ genotypes who showed increased ReHo in the posterior cingulum and the frontal, temporal, and parietal lobes and decreased ReHo in the left corpus callosum, compared with controls with the GG genotypes. The main effect of disease was found in the frontal, parietal, and temporal lobes. The main effect of genotypes was found in the left corpus callosum and the frontal lobe. There was no interaction between rs1545843 genotypes and disease status. We found that the left corpus callosum ReHo was positively correlated with total scores of the Hamilton Depression Scale (HAMD) (p = 0.021), so as was the left inferior parietal gyrus ReHo with cognitive disorder (p = 0.02). In addition, the right middle temporal gyrus had a negative correlation with retardation (p = 0.049).

CONCLUSION: We observed an association between the SLC6A15 rs1545843 and resting-state brain function of the corpus callosum, cingulum and the frontal, parietal, and temporal lobes in MDD patients, which may be involved in the pathogenesis of MDD.

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A Combined Study of SLC6A15 Gene Polymorphism and the Resting-State Functional Magnetic Resonance Imaging in First-Episode Drug-Naive Major Depressive Disorder

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