FAAH, SLC6A4, and BDNF variants are not associated with psychosocial stress and mental health outcomes in a population of Syrian refugee youth

The developmental origins of health and disease (DOHaD) hypothesis posits that early childhood stressors disproportionately impact adult health. Numerous studies have found adult mental health to be associated with childhood adversities and genetic variants, particularly in genes related to neurochemistry. However, few studies have examined the way interactive effects may manifest over time and fewer still include protective factors, like resilience. Our group has previously found associations between the monoamine oxidase A gene, MAOA, and a contextually-specific measure of resilience with a measure of perceived psychosocial stress over time in Syrian refugee youth. In this study, we work with the same sample of adolescents to test genetic variants in three additional candidate genes (FAAH, the 5-HTTLPR region of SLC6A4, and BDNF) for associations with six psychosocial stress and mental health outcomes. Using multi-level modeling, we find no association between variants in these candidate genes and psychosocial stress or mental health outcomes. Our analysis included tests for both direct genetic effects and interactions with lifetime trauma and resilience. Negative results, such as the lack of genetic associations with outcome measures, provides a more complete framework in which to better understand positive results and associations.

健康与疾病的发育起源（developmental origins of health and disease, DOHaD）假说提出，儿童早期应激会对成年健康产生不成比例的影响。已有大量研究表明，成年心理健康与童年逆境及遗传变异存在关联，尤其在与神经化学相关的基因中更为显著。然而，鲜有研究探讨交互效应随时间的表现形式，且纳入心理韧性（resilience）这类保护因素的研究更是少之又少。本团队此前的研究发现，在叙利亚难民青少年群体中，单胺氧化酶A（monoamine oxidase A, MAOA）基因、情境特异性心理韧性测量量表与随时间变化的感知社会心理压力测量结果之间存在关联。本次研究沿用同一青少年队列，对另外三个候选基因（FAAH、SLC6A4基因的5-HTTLPR区域以及BDNF）的遗传变异与6项社会心理压力及心理健康结局指标的关联进行检验。本研究采用多层模型分析，未发现上述候选基因的变异与社会心理压力或心理健康结局之间存在关联。本次分析同时检验了直接遗传效应，以及与终生创伤、心理韧性的交互效应。阴性结果（如未发现遗传变异与结局指标间的关联）为更好地理解阳性结果及关联关系提供了更为完整的研究框架。