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

灵长类动物成年过渡期间不良社会情绪行为的起源和出现

• 批准号: 10256803
• 负责人: Andrew S Fox
• 金额: $ 73.08万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-09 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10256803
• 关键词: 5 year old; Adolescence; Adolescent; Adolescent and Young Adult; Adult; Age; Amygdaloid structure; Animals; Anterior; Anxiety; Anxiety Disorders; Behavior; Behavior assessment; Behavioral; Behavioral inhibition; Brain; Brain imaging; Brothers; California; Cell Nucleus; Clinical Psychology; Code; Complement; Complex; Computer Vision Systems; Coupled; Data; Depressive disorder; Development; Disease; E-learning; Environment; Exposure to; Failure; Family; Female; Foundations; Foxes; Freezing; Functional Magnetic Resonance Imaging; Generations; Genetic; Geography; Heritability; Housing; Human; Individual; Infant; Infant Behavior; Inherited; Insula of Reil; Intervention; Lead; Life; Life Stress; Link; Longitudinal prospective study; Magnetic Resonance Imaging; Measures; Mediating; Mental Depression; Mental disorders; Metabolism; Modeling; Monitor; Network-based; Neurobiology; Pathway interactions; Phenotype; Physiological; Plant Roots; Prefrontal Cortex; Prevalence; Prevention; Primates; Psychiatry; Psychopathology; Puberty; Records; Research; Resources; Rest; Risk; Risk Factors; Sex Differences; Social Behavior; Social Environment; Stress; Structure; Structure of terminal stria nuclei of preoptic region; System; Techniques; Technology; Temperament; Testing; Variant; Work; anxiety symptoms; anxiety-like behavior; anxious temperament; behavioral pharmacology; biobehavior; boys; brain circuitry; child depression; comorbidity; deep learning; deep neural network; depressive symptoms; emerging adult; emotional behavior; fluorodeoxyglucose positron emission tomography; genetic pedigree; girls; imaging study; innovation; insight; longitudinal design; mature animal; midbrain central gray substance; multimodality; neural circuit; neural network; neuroimaging; nonhuman primate; novel; preadolescence; prevent; prospective; relating to nervous system; response; sex; symptomatology; tool; young adult

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.

具体目的：焦虑和抑郁障碍是常见的，共病的，具有挑战性的