ORIGINS AND EMERGENCE OF MALADAPTIVE SOCIOEMOTIONAL BEHAVIOR DURING THE TRANSITION TO ADULTHOOD IN PRIMATES

具体目标：焦虑和抑郁障碍是常见的，共病，并具有挑战性， 治疗，将其列为人类痛苦的最大贡献者之一。早期生活的极端 压抑或焦虑的气质，以行为压抑和极端为特征 对新的和/或潜在的威胁性环境的生理反应，是最强的之一 焦虑和抑郁症后期发展的预测因子。了解 这种早期生命风险的神经生物学将确定治疗目标，并提供一个独特的机会， 开发有科学依据的行为和药理干预措施， 预防压力相关的精神病理学在这里，我们提出了一个前瞻性的纵向研究， 非人灵长类动物（NHP）了解先天风险因素和早期生活抑制如何导致 青少年和成年早期的焦虑和适应不良的社会行为。我们会这样做 通过利用加州国家灵长类动物研究中心（CNPRC）的资源， 包括以前对行为抑制的早期评估，一个多代同堂的家庭， 血统，和大型户外住房，以及尖端的工具和分析技术， 包括多模式神经成像和基于神经网络的动物跟踪和行为 分析。我们将采用前瞻性纵向设计，并选择176个NHP（88 F 从CNPRC的大型，多代， 家族血统为了研究类似焦虑和抑郁的精神病学的出现， 国家卫生保健中心将是“青少年”，一半将是“青年人”。我们将在实验室内进行行为 和神经影像学评估，以及纵向大规模监测动物导航， 整个社会地理环境。首先，我们将研究遗传风险和早期- 在生态有效的环境中，生活抑制会导致不适应的社会情绪行为 在青春期和成年早期（目标1）。从青春期开始，焦虑症的风险 对女孩来说比男孩大。因此，我们还旨在展示青少年和成年人 焦虑和抑郁样行为的性别差异（目标2）。为了了解这些 这些因素是由相关脑回路的改变介导的，包括杏仁核的延伸， 每只动物将经历多模式结构和功能神经成像评估。使用 这些数据，我们将测试特定的假设，在何种程度上延伸杏仁核 回路将早期生活抑制与焦虑和抑郁样行为的进展联系起来（Aim 3）。这种方法的结合有望为神经系统提供前所未有的洞察力。 适应不良的社会情绪行为的基质在过渡到成年。

Specific Aims: Anxiety and depressive disorders are common, comorbid, and challenging to treat, ranking them among the greatest contributors to human suffering. An early-life extreme inhibited or anxious temperament, characterized by behavioral inhibition and extreme physiological responses to novel and/or potentially threatening contexts, is among the strongest predictors of the later development of anxiety and depressive disorders. Understanding the neurobiology of this early-life risk will identify treatment targets and provide a unique opportunity to develop scientifically founded behavioral and pharmacological interventions to treat and prevent stress-related psychopathology. Here, we propose a prospective longitudinal study in nonhuman primates (NHPs) to understand how inborn risk-factors and early-life inhibition lead to anxiety and maladaptive social behavior during adolescence and early adulthood. We will do this by leveraging the resources at the California National Primate Research Center (CNPRC), including previous early-life assessments of behavioral inhibition, a multi-generational family pedigree, and large outdoor housing, alongside cutting-edge tools and analysis techniques, including multimodal neuroimaging and neural network-based animal tracking and behavioral analyses. We will use a prospective longitudinal design, and select 176 NHPs (88 F) previously phenotyped for early-life inhibition (3-4 months old) from the CNPRC’s large, multi-generational family pedigree. To study the emergence of anxiety- and depression-like symptomatology, half of the NHPs will be "adolescents" and half will be "young adults". We will perform in-lab behavioral and neuroimaging assessments, and longitudinal large-scale monitoring as animals navigate the entirety of their socio-geographic environment. First, we will examine how heritable-risk and early- life inhibition contribute to maladaptive socio-emotional behaviors in ecologically-valid contexts during adolescence and early adulthood (Aim 1). Starting in puberty, the risk for anxiety disorders is greater for girls than boys. Therefore, we also aim to demonstrate adolescent and young-adult sex differences in anxiety- and depression-like behaviors (Aim 2). To understand how these factors are mediated by alterations in relevant brain circuitry, including the extended amygdala, each animal will undergo multimodal structural and functional neuroimaging assessments. Using these data, we will test specific hypotheses regarding the extent to which extended amygdala circuits link early-life inhibition to the progression of anxiety- and depression-like behaviors (Aim 3). This combination of approaches promises to provide unprecedented insight into the neural substrates of maladaptive socio-emotional behavior during the transition to adulthood.