Gray Matter Volume Reductions Were Associated with TPH1 Polymorphisms in Depressive Disorder Patients with Suicidal Attempts

Abstract

Objective: Structural changes of brain areas have been reported in depressive disorder and suicidal behavior (SB), in which TPH1 also has been known as a promising candidate gene. We investigated gray matter volume (GMV) differences, TPH1 rs1800532 and rs1799913 polymorphisms previously found to be associated with depressive disorder and SB, and the relationship between the two markers.

Methods: Thirteen depressive disorder patients with suicidal attempts (SA) and twenty healthy controls were included. We examined GMV differences using a voxel-based morphometry and regions of interest analysis. Direct sequencing was used for genotyping.

Results: The patients showed significant GMV reduction in left cerebral region including middle frontal gyrus, inferior frontal gyrus, and anterior cingulate cortex; in right middle temporal gyrus; in left cerebellar tonsil; and in right cerebral region including precentral gyrus and postcentral gyrus (corrected p<0.005). The right precentral and postcentral gyri GMV values of AA and CA genotypes patients were significantly decreased compared to those of CC genotype subjects (corrected p=0.040).

Conclusion: These findings show the possibility that both GMV reductions and TPH1 rs1800532/rs1799913 A allele may be involved in the pathogenesis of depressive disorder patients with SA.

Keywords: Depressive disorder; Gray matter volume; Suicidal attempt; TPH1 gene.

Figure 1.

Regions of interest (ROIs) to be shown as significant gray matter volume reduction in the patients compared to the controls. (A) is ROI 1 including left middle frontal gyrus (x=-28, y=48, z=-1), inferior frontal gyrus (x=-38, y=44, z=-7), and anterior cingulate cortex (x=-26, y=44, z=4); (B) is ROI 2, right middle temporal gyrus (x=63, y=-47, z=8); (C) is ROI 3, left cerebellar tonsil (x=-28, y=-57, z=-49); and (D) is ROI 4 including right precentral gyrus (x=37, y=-17, z=66) and postcentral gyrus (x=33, y=-23, z=70).

Figure 2.

Comparison of gray matter volume (GMV) values in the right precentral and postcentral gyri between A-carriers and CC genotype subjects in the patients. Differences were analyzed with t-test. ^*corrected p value by Bonferroni method is 0.040. GMV of region of interest 4 (ROI 4) is gray matter volume values of the right precentral and postcentral gyri; A-carrier, the subjects with AA and CA genotypes; CC, the subjects with CC genotype.