Serotonergic multilocus genetic variation moderates the association between interpersonal relationship and adolescent depressive symptoms

Abstract

BackgroundResearch suggests that genetic variants linked to serotonin functioning moderate the association between environmental stressors and depressive symptoms, but examining gene–environment interactions with single polymorphisms limits power. MethodsA multilocus genetic profile score (MGPS) approach to measuring serotonergic multilocus genetic variation and examined interactions with interpersonal relationship, insomnia with depressive symptoms as outcomes in an adolescent sample (average age = 14.15 ± 0.63 years since first measurement; range: 13 to 15). Results(1) interpersonal relationship predicted adolescent depressive symptoms; (2) insomnia mediated the effect of interpersonal relationships on adolescent depressive symptoms; (3) the THP2 gene rs4570625 polymorphism G allele was a key risk factor for depressive symptom, and the MGPS moderated the effects of teacher-student relationship and insomnia on adolescent depressive symptom. Specifically, as the MGPS increased, the effects of insomnia on adolescent depressive symptom were enhanced; further, when the MGPS score increased, the effect of teacher-student relationship on depression showed a similar phenomenon with an increased slope and enhanced prediction; and (4) the results of sensitivity analysis showed that multilocus genetic interaction with the environment had a better explanatory power and stability for depression than single polymorphism studies. ConclusionMGPS provides substantial power to examine gene–environmental interactions linked to affective outcomes among adolescents.