Development of Adolescent Depression: Genes, Temperament and Gender Differences

描述（由申请人提供）：抑郁症是疾病相关残疾的主要原因，并对身心健康产生重大影响。纵向研究表明，抑郁症在青春期急剧增加，特别是女孩。本研究将利用来自威斯康星州家庭与工作研究（WSFW）的数据，对400名儿童及其家庭进行纵向研究，以测试抑郁症发展的遗传和气质模型以及抑郁症的性别差异。将使用适用于纵向数据集的统计技术分析模型，包括潜在生长曲线模型。具体目标是：1）检测5-HTTLPR的短等位基因和MAOA-uVNTR的三重复等位基因与负性生活事件的相互作用是否预测青春期更多的抑郁症状和障碍; 2）检测更高的负性情感与负性生活事件的相互作用是否预测青春期更多的抑郁症状和障碍; 3）检查遗传变异对抑郁症的影响是否由消极情感介导，消极情感反过来与消极生活事件相互作用以预测抑郁症;和4）评估抑郁症性别差异出现的可能解释：a）在MAOA-uVNTR的情况下，这是X连锁的，如果风险等位基因是显性或共显性的，女孩可能具有更大的遗传易感性抑郁症; B）存在气质的性别差异，导致更多的女孩比男孩具有赋予抑郁症易感性的气质; c）从青春期开始，女孩比男孩经历更多的负面生活事件;或d）由显著的性别互动所表明的复杂性别差异表明女孩和男孩抑郁的不同途径。与NIH关注了解精神障碍的原因相对应，这项研究将有助于了解抑郁症的发展，特别是抑郁症中出现的性别差异，以告知和改善抑郁症的预防和治疗。公共卫生相关性：这项研究的目的是更好地了解抑郁症在青春期发展的过程，特别是为什么女性比男性更容易患上抑郁症。这些知识将有助于研究人员和临床医生制定预防措施和治疗计划

DESCRIPTION (provided by applicant): Depression is a major cause of disease-related disability and confers substantial consequences to physical and psychological health. Longitudinal research indicates that depression increases dramatically in adolescence, particularly for girls. The present study will draw upon data from the Wisconsin Study of Families and Work (WSFW), a longitudinal study of 400 children and their families, to test genetic and temperament models of the development of depression and emergence of a gender difference in depression. Models will be analyzed using statistical techniques appropriate for longitudinal data sets, including latent growth curve models. Specific aims are: 1) Examine whether the short allele of 5-HTTLPR and the three-repeat allele of MAOA- uVNTR, in interaction with negative life events, predict more depressive symptoms and disorders in adolescence; 2) Examine whether higher negative affectivity, in interaction with negative life events, predicts more depressive symptoms and disorders in adolescence; 3) Examine whether the effects of genetic variation on depression are mediated by negative affectivity, which in turn interacts with negative life events to predict depression; and 4) Evaluate possible explanations for the emergence of a gender difference in depression: a) in the case of MAOA-uVNTR, which is X-linked, girls may have greater genetic vulnerability to depression if the risk allele is dominant or co-dominant; b) there exist gender differences in temperament that result in more girls than boys having a temperament that confers vulnerability to depression; c) beginning in adolescence, girls experience more negative life events than do boys; or d) complex gender differences indicated by significant gender interactions signal different pathways to depression for girls and boys. Corresponding to NIH concerns to understand the causes of mental disorders, this research will aid understandings of the development of depression, and in particular the emergence of a gender difference in depression, to inform and improve prevention and treatment of depression. PUBLIC HEALTH RELEVANCE: The goal of this research is to better understand the processes through which depression develops in adolescence, and in particular, the reasons why females are more likely than males to experience depression. This knowledge will aid researchers and clinicians in their development of prevention efforts and treatment plans