Adolescent trauma produces enduring disruptions in sleep architecture that lead to increased risk for adult mental illness

童年创伤是已知的最大的环境因素之一，可以增加广泛的风险。 成人精神疾病童年创伤的后果不仅会影响患精神疾病的风险， 但显著改变症状复杂性并预测诊断类别内的治疗抗性。它可以 有人认为，睡眠障碍是已知的最大的驱动力（其他是吃，喝，性）， 成人精神疾病风险增加。睡眠异常与几乎所有的精神疾病同时发生， 像青少年创伤一样，显著地改变了疾病的轨迹、严重性和复杂性。每个 睡眠结构的组成部分有助于认知，情绪和身体健康。例如， 运动睡眠（REM）在处理情感和情绪信息方面起着关键作用， 关键是参与“去增强”压力事件的情绪负荷，改善其自主神经功能。 唤醒负担最近的一份报告强烈表明，激活头内侧被盖核（RMTg）， 可以通过腹侧被盖区（VTA）的主要输出显著减少REM睡眠。这一发现 有趣的是，因为我们的实验室最近暗示RMTg激活介导的适应不良的成年后果， 青春期压力在青春期，RMTg的激活和随后的REM缺陷可能会导致戏剧性的 因为睡眠和昼夜节律过程有助于驱动和引导神经元发育。 我们将利用青少年暴露于行为学相关的压力（活的捕食者）来测试以下内容 假设：1）青少年暴露于行为学相关的压力导致成分的持久变化- 与成年期适应不良行为相关的特定睡眠结构，以及2）青少年压力- 诱导的RMTg功能变化是与适应不良相关的睡眠结构变化的基础。 成年后的行为特征AIM 1的目的是确定青少年的个人睡眠状况是否与青少年的睡眠状况有关。 在一组旨在评估抑郁和焦虑测试中，压力可以预测成年人的行为。我们将 描述青春期和成年期的睡眠结构，然后描述 成年我们希望青少年压力后睡眠结构的个体差异可以预测 正常的、适应不良的和抗压力的成年人行为特征。AIM 2的目标是测试功能角色 RMTg-VTA回路介导睡眠结构紊乱和/或青少年压力引起的 成年后的适应不良行为交叉化学遗传学（DREADD）方法将用于 专门抑制RMTg-VTA电路，以测试因果关系。青少年时期的创伤- 诱发的睡眠障碍可能是导致成人精神疾病的主要因素。调查 睡眠结构和潜在神经生物学的特定改变将有助于促进治疗发现 努力

Childhood trauma is one of the single greatest environmental factors known to increase risk for a broad range of adult psychiatric illnesses. The consequences of childhood trauma not only affect the risk for mental illness, but significantly alter symptom complexity and predict treatment resistance within a diagnostic category. It could be argued that sleep disturbance is the single greatest drive (others being eating, drinking, sex) known to increase risk for adult psychiatric illness. Sleep abnormalities co-occur with virtually all psychiatric illnesses and, like adolescent trauma, significantly worsens the trajectory, severity and complexity of the illness. Each component of sleep architecture contributes to cognitive, emotional and somatic health. For example, rapid-eye movement sleep (REM), plays a key role in processing affective, emotional information and is thought to be critically involved in ‘depotentiating’ the emotional charge of a stress event and ameliorating its autonomic arousal burden. A recent report strongly suggests that activation of the rostromedial tegmental nucleus (RMTg) can dramatically decrease REM sleep via its main output to the ventral tegmental area (VTA). This finding is intriguing since our lab recently implicated RMTg activation in mediating the maladaptive adult consequences of adolescent stress. RMTg activation and subsequent REM deficits during adolescence could have dramatic impact since sleep and circadian processes help drive and guide neuronal development. We will utilize adolescent exposure to an ethologically-relevant stress (live predator) to test the following hypotheses: 1) Adolescent exposure to ethologically-relevant stress results in enduring changes in component- specific sleep architecture that are associated with maladaptive behavior in adulthood, and 2) Adolescent stress- induced changes in RMTg function underly the changes in sleep architecture associated with maladaptive behavioral profiles in adulthood. The goal of AIM 1 is to determine if individual sleep profiles following adolescent stress are predictive of adult behavior in a panel of tests designed to assess depression and anxiety. We will characterize sleep architecture in adolescence and adulthood and then characterize behavior profiles in adulthood. We expect individual differences in sleep architecture following adolescent stress to be predictive of normal, maladaptive and stress-resilient adult behavioral profiles. The goal of AIM 2 is to test the functional role of the RMTg-VTA circuit in mediating disturbed sleep architecture and/or changes in adolescent stress-induced maladaptive behavior in adulthood. An intersectional chemogenetic (DREADD) approach will be used to specifically inhibit the RMTg-VTA circuit in order to test causal associations. Adolescent childhood trauma- induced sleep disturbance may be a primary factor in the trajectory towards adult mental illness. Investigating the specific alterations in sleep architecture and underlying neurobiology will help facilitate therapeutic discovery efforts.