Effect of tryptophan hydroxylase-2 gene variants on amygdalar and hippocampal volumes
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- 作者：Hideyuki Inoue ; Hidenori Yamasue ; Mamoru Tochigi ; Kunio Takei ; Motomu Suga ; Osamu Abe ; Haruyasu Yamada ; Mark A. Rogers ; Shigeki Aoki ; Tsukasa Sasaki ; Kiyoto Kasai
- 关键词：Tryptophan hydroxylase 2 (TPH2) ; Amygdala ; Hippocampus ; Endophenotype ; Manual tracing ; Temperament and Character Inventory (TCI)
- 刊名：Brain Research
- 出版年：2010
- 出版时间：17 May 2010
- 年：2010
- 卷：1331
- 期：Complete
- 页码：51-57
- 全文大小：241 K
文摘
Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin (5-HT). Genetic variations in human TPH2, a newly identified isoform of TPH, have been shown to impact on enzymatic activity of TPH and to be associated with emotion-related personality traits and mood/anxiety disorders. Identification of an intermediate phenotype that bridges the relationship between genes and behavior may be of great importance in the further clarification of how hTPH2 contributes to emotional regulation. Previous studies have shown that a polymorphism in the upstream regulatory region of hTPH2 (SNP G-703T, rs4570625) correlates functional MRI response of the amygdala. In this study, we examined the effect of this genotype on amygdalar and hippocampal volumes in 208 mentally healthy individuals. To measure volumes of amygdala and hippocampus, gray matter regions of interest were outlined manually on three-dimensional MRI data obtained using a 1.5-T scanner. Additionally, personality traits were evaluated using the Temperament and Character Inventory (TCI). Those subjects with T allele carriers were associated with significantly smaller volumes in bilateral amygdala and hippocampus and higher reward dependence than those with G allele homozygotes. These results suggest that amygdalar and hippocampal volumes assessed using MRI may be a useful intermediate phenotype that will uncover the biological pathway linking 5-HT synthesis and emotional behaviors and affective disorders.