Psychobiological Mechanisms Underlying the Association Between Early Life Stress and Depression Across Adolescence

摘要 青春期过渡的特点是症状和发病率显著增加， 萧条事实上，大多数MDD的首次发作发生在青春期。的四分之一 青少年在其青少年时期结束时经历严重抑郁症（MDD）的发作， 几乎一半的青少年抑郁症发作在三年内复发。在 研究人员试图找出导致青少年抑郁症高发的因素， 集中在童年时期或早期生活压力的负面影响 （ELS）。ELS，包括虐待，忽视，失去父母和人际压力，与一个显著的 增加后续抑郁症的风险。然而，我们还不了解 ELS助长了这一风险，从而阻碍了对青少年的有效预防和干预工作。的 拟议的项目旨在研究两个心理生物学机制的轨迹，可以解释 ELS如何增加青春期抑郁症的风险：增加的压力反应和迟钝的奖励 灵敏度这种对压力和奖励系统轨迹的关注在青春期尤为突出 鉴于这两个系统都在这一敏感时期经历了重大变化和重组， 发展我们建议纵向跟踪220名已经完成两个 全面评估（从9至12岁开始），间隔两年，评估他们对ELS的接触情况， 心理生物学功能（包括对压力的行为、认知、内分泌和神经评估 反应性和奖赏敏感性），以及MDD症状和诊断。我们将利用从中获得的数据， 一个大的和丰富的儿童样本，前瞻性地研究发展机制， ELS影响青春期抑郁症的发病和病程。具体来说，我们将整合数据 从参与者在儿童晚期和青少年早期完成的前两次评估中获得了新的数据， 我们建议在青少年中期和后期进行两次额外的评估， MDD发病率达到高峰的发育期。具体而言，我们将继续评估 临床特征、信息处理偏差、内分泌功能和脑功能、结构和 连通性。总的来说，这种方法将使我们能够分析ELS对轨道的影响， 从儿童期到青春期后期的心理生物学和临床功能，以及 这些结构的规范轨迹。该项目的调查结果将为制定个性化服务的努力提供参考 目标，以便为暴露于ELS的青少年制定预防和治疗计划 因此，这些人有患MDD的高风险。

ABSTRACT The transition through adolescence is characterized by a striking increase in symptoms and rates of depression. In fact, the majority of first episodes of MDD occur during adolescence. One-quarter of adolescents experience an episode of Major Depressive Disorder (MDD) by the end of their teenage years, and almost half of adolescents with a depressive episode experience a recurrence within three years. In attempting to identify factors that contribute to this high prevalence of depression in adolescence, investigators have focused on the adverse effects of exposure to stress occurring during childhood, or early life stress (ELS). ELS, including abuse, neglect, parental loss, and interpersonal stress, is associated with a marked increase in risk for subsequent depression. We do not yet understand, however, the mechanisms by which ELS contributes to this risk, thus hampering effective prevention and intervention efforts with adolescents. The proposed project is designed to examine trajectories of two psychobiological mechanisms that may explain how ELS increases risk for depression during adolescence: increased stress reactivity and blunted reward sensitivity. This focus on the trajectories of stress and reward systems is particularly salient in adolescence given that both of these systems undergo significant change and reorganization during this sensitive period of development. We propose to follow longitudinally 220 boys and girls who have already completed two comprehensive assessments (beginning at 9 to 12 years of age), two years apart, of their exposure to ELS, psychobiological functioning (including behavioral, cognitive, endocrine, and neural assessments of stress reactivity and reward sensitivity), and MDD symptoms and diagnosis. We will leverage data obtained from this large and richly-characterized sample of children to examine prospectively the developmental mechanisms by which ELS affects the onset and course of depression during adolescence. Specifically, we will integrate data from the participants’ first two assessments completed in late childhood and early adolescence with new data that we propose to obtain at two additional assessments conducted in mid and late adolescence, a developmental period during which the incidence of MDD peaks. Specifically, we will continue to assess clinical characteristics, information-processing biases, endocrine functioning, and brain function, structure, and connectivity. Collectively, this approach will allow us to analyze the effects of ELS on trajectories of psychobiological and clinical functioning from childhood through late adolescence, and on deviations from normative trajectories of these constructs. Findings from this project will inform efforts to generate personalized targets in order to tailor prevention and treatment programs to adolescents who have been exposed to ELS and who, consequently, are at high risk for developing MDD.