Institute of Psychological Research (IIP), University of Costa Rica (UCR), 2060 San José, Costa Rica; Institute for Health Research (INISA), University of Costa Rica (UCR), 2060 San José, Costa Rica.
Institute of Evolutionary Biology (IBE), Barcelona Biomedical Research Park (PRBB), E-08003 Barcelona, Spain.
Psychiatry Res. 2016 Oct 30;244:71-7. doi: 10.1016/j.psychres.2016.07.032. Epub 2016 Jul 20.
Alterations in the monoaminergic neurotransmission systems are suspected to be involved in the etiology of neuropsychiatric disorders, including depression. The role of these pathways in the risk of developing depressive symptoms during childhood or adolescence is still not completely clear. This study sought to identify putative genetic factors in genes of serotonergic and dopaminergic systems modulating the level of manifestation of depressive symptoms in children and adolescents. We analyzed 170 single nucleotide polymorphisms (SNPs) in 21 candidate dopaminergic and serotonergic genes in a non-clinical sample of 410 Costa Rican participants of ages between 7 and 18 years, assessing the severity of depressive symptoms through the Child Depression Inventory (CDI). Genotypic and haplotypic associations, as well as epistatic effects, were examined. A significant interaction effect was detected between rs1039089 in conjunction with rs877138 located upstream of the dopamine D1 receptor (DRD1) and the dopamine D2 receptor (DRD2) genes respectively, although no evidence was found for any single variant or haplotype related to a differential liability. This newly described genetic interaction among putative regulatory regions of dopamine receptors could affect the level of manifestation of depressive symptoms through an imbalance of D1-D2 heteromers and modulation of cognitive processes.
单胺能神经递质系统的改变被怀疑与神经精神疾病的病因有关，包括抑郁症。这些途径在儿童或青少年时期发展为抑郁症状的风险中的作用尚不完全清楚。本研究旨在确定调节儿童和青少年抑郁症状表现水平的 5-羟色胺能和多巴胺能系统基因中的假定遗传因素。我们在一个非临床样本中分析了 21 个候选多巴胺能和 5-羟色胺能基因中的 170 个单核苷酸多态性（SNP），该样本由来自哥斯达黎加的 410 名年龄在 7 至 18 岁之间的参与者组成，通过儿童抑郁量表（CDI）评估抑郁症状的严重程度。检查了基因型和单倍型关联以及上位效应。尽管没有发现与差异易感性相关的任何单一变体或单倍型的证据，但在多巴胺 D1 受体（DRD1）和多巴胺 D2 受体（DRD2）基因的上游分别位于 rs1039089 与 rs877138 之间检测到了显著的相互作用效应。这种新描述的多巴胺受体假定调节区域之间的遗传相互作用可能通过 D1-D2 异源二聚体的失衡和认知过程的调节来影响抑郁症状的表现水平。
