Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Ellernholzstraße 1-2, 17475, Greifswald, Germany.
Molecular Systems Physiology Group, National University of Ireland, Galway, Ireland.
Sci Rep. 2020 Dec 28;10(1):22394. doi: 10.1038/s41598-020-79388-7.
A complex interplay between genetic and environmental factors determines the individual risk of depressive disorders. Vitamin D has been shown to stimulate the expression of the tryptophan hydroxylase 2 (TPH2) gene, which is the rate-limiting enzyme for serotonin production in the brain. Therefore, we investigate the hypothesis that serum vitamin D levels moderate the interaction between the serotonin transporter promotor gene polymorphism (5-HTTLPR) and childhood abuse in depressive disorders. Two independent samples from the Study of Health in Pomerania (SHIP-LEGEND: n = 1 997; SHIP-TREND-0: n = 2 939) were used. Depressive disorders were assessed using questionnaires (BDI-II, PHQ-9) and interview procedures (DSM-IV). Besides serum vitamin D levels (25(OH)D), a functional polymorphism (rs4588) of the vitamin D-binding protein is used as a proxy for 25(OH)D. S-allele carriers with childhood abuse and low 25(OH)D levels have a higher mean BDI-II score (13.25) than those with a higher 25(OH)D level (9.56), which was not observed in abused LL-carriers. This significant three-way interaction was replicated in individuals with lifetime major depressive disorders when using the rs4588 instead of 25(OH)D (p = 0.0076 in the combined sample). We conclude that vitamin D relevantly moderates the interaction between childhood abuse and the serotonergic system, thereby impacting vulnerability to depressive disorders.
遗传和环境因素的复杂相互作用决定了个体患抑郁障碍的风险。维生素 D 已被证明可刺激色氨酸羟化酶 2（TPH2）基因的表达，该基因是大脑中 5-羟色胺产生的限速酶。因此，我们假设血清维生素 D 水平可以调节 5-羟色胺转运体启动子基因多态性（5-HTTLPR）与儿童期虐待在抑郁障碍中的相互作用。使用来自波罗的海健康研究（SHIP-LEGEND：n=1997；SHIP-TREND-0：n=2939）的两个独立样本。使用问卷（BDI-II、PHQ-9）和访谈程序（DSM-IV）评估抑郁障碍。除了血清维生素 D 水平（25（OH）D）外，维生素 D 结合蛋白的功能多态性（rs4588）也被用作 25（OH）D 的替代物。携带 S 等位基因且有儿童期虐待和低 25（OH）D 水平的个体的 BDI-II 评分（13.25）高于那些有较高 25（OH）D 水平的个体（9.56），但在有儿童期虐待的 LL 携带者中未观察到这种情况。当使用 rs4588 而不是 25（OH）D 时，这种显著的三向相互作用在有终生重性抑郁障碍的个体中得到了复制（在合并样本中 p=0.0076）。我们得出结论，维生素 D 可显著调节儿童期虐待与 5-羟色胺能系统之间的相互作用，从而影响抑郁障碍的易感性。
