Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.
Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
Transl Psychiatry. 2023 Jun 15;13(1):208. doi: 10.1038/s41398-023-02506-2.
Variants within the monoamine oxidase A (MAO-A, MAOA) and tryptophan hydroxylase 2 (TPH2) genes, the main enzymes in cerebral serotonin (5-HT) turnover, affect risk for depression. Depressed cohorts show increased cerebral MAO-A in positron emission tomography (PET) studies. TPH2 polymorphisms might also influence brain MAO-A because availability of substrates (i.e. monoamine concentrations) were shown to affect MAO-A levels. We assessed the effect of MAOA (rs1137070, rs2064070, rs6323) and TPH2 (rs1386494, rs4570625) variants associated with risk for depression and related clinical phenomena on global MAO-A distribution volume (V) using [C]harmine PET in 51 participants (21 individuals with seasonal affective disorder (SAD) and 30 healthy individuals (HI)). Statistical analyses comprised general linear models with global MAO-A V as dependent variable, genotype as independent variable and age, sex, group (individuals with SAD, HI) and season as covariates. rs1386494 genotype significantly affected global MAO-A V after correction for age, group and sex (p < 0.05, corr.), with CC homozygotes showing 26% higher MAO-A levels. The role of rs1386494 on TPH2 function or expression is poorly understood. Our results suggest rs1386494 might have an effect on either, assuming that TPH2 and MAO-A levels are linked by their common product/substrate, 5-HT. Alternatively, rs1386494 might influence MAO-A levels via another mechanism, such as co-inheritance of other genetic variants. Our results provide insight into how genetic variants within serotonin turnover translate to the cerebral serotonin system. Clinicaltrials.gov Identifier: NCT02582398. EUDAMED Number: CIV-AT-13-01-009583.
单胺氧化酶 A（MAOA，MAOA）和色氨酸羟化酶 2（TPH2）基因内的变体是大脑 5-羟色胺（5-HT）代谢的主要酶，它们会影响抑郁的风险。正电子发射断层扫描（PET）研究表明，抑郁队列的大脑 MAOA 增加。TPH2 多态性也可能影响大脑 MAOA，因为底物（即单胺浓度）的可用性被证明会影响 MAOA 水平。我们评估了与抑郁风险和相关临床现象相关的 MAOA（rs1137070、rs2064070、rs6323）和 TPH2（rs1386494、rs4570625）变体对全球 MAO-A 分布容积（V）的影响，使用 [C]harmine PET 在 51 名参与者（21 名季节性情感障碍（SAD）患者和 30 名健康个体（HI））中进行了评估。统计分析包括以全球 MAO-A V 为因变量、基因型为自变量、年龄、性别、组（SAD 患者、HI）和季节为协变量的一般线性模型。rs1386494 基因型在校正年龄、组和性别后显著影响全球 MAO-A V（p < 0.05，校正），CC 纯合子的 MAO-A 水平升高 26%。rs1386494 对 TPH2 功能或表达的作用知之甚少。我们的结果表明，rs1386494 可能会对 TPH2 产生影响，因为 TPH2 和 MAO-A 水平可能通过其共同产物/底物 5-HT 相关联。或者，rs1386494 可能通过另一种机制（例如其他遗传变异的共同遗传）影响 MAO-A 水平。我们的结果提供了关于色氨酸代谢过程中的遗传变异如何转化为大脑 5-羟色胺系统的见解。临床试验.gov 标识符：NCT02582398。EUDAMED 编号：CIV-AT-13-01-009583。
