Vitamin D moderates the interaction between 5-HTTLPR and childhood abuse in depressive disorders

• Published in: Scientific reports Vol. 10; no. 1; pp. 22394 - 9
• Main Authors: Bonk, Sarah, Hertel, Johannes, Zacharias, Helena U., Terock, Jan, Janowitz, Deborah, Homuth, Georg, Nauck, Matthias, Völzke, Henry, Meyer zu Schwabedissen, Henriette, Van der Auwera, Sandra, Grabe, Hans Jörgen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.12.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114/2415; 631/208; 692/499; 692/53; 692/699/476/1414; Abuse; Adult; Child; Child Abuse; Child abuse & neglect; Children; Depressive Disorder, Major - blood; Depressive Disorder, Major - etiology; Depressive Disorder, Major - genetics; Environmental factors; Female; Gene polymorphism; Humanities and Social Sciences; Humans; Male; Mental depression; Mental disorders; Middle Aged; multidisciplinary; Polymorphism; Polymorphism, Genetic; Science; Science (multidisciplinary); Serotonin; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin transporter; Tryptophan; Tryptophan hydroxylase; Vitamin D; Vitamin D - blood; Vitamin D-binding protein; Vitamin D-Binding Protein - genetics
• ISSN: 2045-2322; 2045-2322
• 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.