Development of Adolescent Depression: Genes, Temperament and Gender Differences

描述(申请人提供)：抑郁症是与疾病相关的残疾的主要原因，并对身心健康造成重大后果。纵向研究表明，抑郁症在青春期急剧增加，尤其是对女孩来说。这项研究将利用威斯康星州家庭和工作研究(WSFW)的数据，这是一项对400名儿童及其家庭进行的纵向研究，以测试抑郁症发生和出现性别差异的遗传和气质模型。模型将使用适用于纵向数据集的统计技术进行分析，包括潜在增长曲线模型。具体目标是：1)检验5-HTTLPR的短等位基因和MAOA-uVNTR的三重复等位基因是否与负性生活事件相互作用，预测青春期更多的抑郁症状和障碍；2)检验较高的负性情感是否与负性生活事件相互作用，预测青春期更多的抑郁症状和障碍；3)检验基因变异对抑郁的影响是否通过负性情感中介，负性情感反过来与负性生活事件相互作用，预测抑郁；以及4)评估抑郁症中出现性别差异的可能原因：a)在X连锁的MAOA-uVNTR的情况下，如果风险等位基因是显性的或共显性的，女孩可能更容易患抑郁症；b)气质上存在性别差异，导致女孩的气质比男孩更容易患抑郁症；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)显著的性别互动表明女孩和男孩患抑郁症的途径不同。与NIH关注的了解精神障碍的原因相对应，本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，以告知和改进抑郁症的预防和治疗。公共卫生相关性：这项研究的目标是更好地了解青春期抑郁症的发展过程，特别是女性比男性更有可能经历抑郁症的原因。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