Department of Psychiatry, Korea University, Seoul, South Korea.
Behav Brain Res. 2012 May 16;231(1):105-10. doi: 10.1016/j.bbr.2012.03.001.
Genetic variation in human tryptophan hydroxylase 2 (TPH2) influences TPH enzymatic activity and is associated with emotion-related traits and mood disorders. The present study investigated the effect of the TPH2 G-703T polymorphism on regional brain volume, assessed using voxel-based morphometry (VBM), and anger traits in mentally healthy individuals. We examined 63 healthy subjects to investigate structural abnormalities using a 1.5-T magnetic resonance imaging system, which was normalized to a customized T1 template and segmented with VBM. The VBM data were analyzed using an analysis of covariance, with age as a covariate. All subjects were assessed with the state-trait anger expression inventory (STAXI) and genotyped for TPH2 G-703T. The subjects with G/G genotype had significantly higher anger control (AX-Con) anger scores than T allele carriers (G/T and T/T genotype). There was a negative correlation between the anger out (AX-Out) and trait anger (T-Ang) scores and gray matter concentration (GMC) in the inferior orbitofrontal cortex (OFC) and hippocampus. Compared to T allele carriers, subjects with the G/G genotype had significantly lower GMC in the inferior OFC. Our findings suggest that OFC is an intermediate phenotype that bridges serotonin synthesis and anger-related traits. The mechanism underlying the effect of the TPH2 gene on OFC abnormality, however, may be complex and may involve several processes related to anger expression.
人类色氨酸羟化酶 2（TPH2）的遗传变异影响 TPH 酶活性，并与情绪相关特征和情绪障碍有关。本研究通过体素形态计量学（VBM）调查了 TPH2 G-703T 多态性对区域脑容量的影响，并在心理健康个体中调查了愤怒特征。我们检查了 63 名健康受试者，使用 1.5-T 磁共振成像系统来研究结构异常，该系统使用 VBM 归一化为自定义 T1 模板并进行分割。使用协方差分析对 VBM 数据进行分析，年龄为协变量。所有受试者均使用状态特质愤怒表达量表（STAXI）进行评估，并对 TPH2 G-703T 进行基因分型。与 T 等位基因携带者（G/T 和 T/T 基因型）相比，具有 G/G 基因型的受试者具有明显更高的愤怒控制（AX-Con）愤怒评分。愤怒外显（AX-Out）和特质愤怒（T-Ang）评分与下眶额皮质（OFC）和海马体的灰质浓度（GMC）呈负相关。与 T 等位基因携带者相比，具有 G/G 基因型的受试者下 OFC 的 GMC 明显降低。我们的研究结果表明，OFC 是一种中介表型，它连接了 5-羟色胺合成和与愤怒相关的特征。然而，TPH2 基因对 OFC 异常的影响的机制可能很复杂，可能涉及与愤怒表达相关的几个过程。
