Progressive social withdrawal in trauma-exposed older adolescents and young adults: neurocircuitry predictors

遭受创伤的老年青少年和年轻人的渐进性社交退缩：神经回路预测因素

• 批准号: 10360875
• 负责人: ELIZABETH OLSON
• 金额: $ 50.54万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10360875
• 关键词: 20 year old; Accelerometer; Adolescent; Adolescent and Young Adult; Adult; Age; Alcohol consumption; Alcohol withdrawal syndrome; Amygdaloid structure; Anhedonia; Automobile Driving; Behavioral; Biological Markers; Brain region; Categories; Cellular Phone; Characteristics; Clinical; Code; Data; Data Collection; Development; Diagnostic; Ecological momentary assessment; Emotions; Enrollment; Evolution; Exposure to; Extinction (Psychology); Face; Frequencies; Fright; Functional Magnetic Resonance Imaging; Future; Health; Human; Immune response; Impairment; Incentives; Individual; Intervention; Interview; Lead; Literature; Location; Loneliness; Longevity; Machine Learning; Major Depressive Disorder; Measures; Mental Health; Mental disorders; Metadata; Modeling; National Institute of Mental Health; Neurobiology; Nucleus Accumbens; Outcome; Participant; Pathologic; Patient Self-Report; Phenotype; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Psychopathology; Recording of previous events; Research; Rest; Rewards; Risk; Risk Factors; Role; Sampling; Social Behavior; Social Interaction; Social Network; Specific qualifier value; Structure; Text; Time; Trauma; Well in self; Withdrawal; Work; base; cardiovascular risk factor; density; depressive symptoms; digital; disability; follow-up; functional MRI scan; innovation; learning strategy; longitudinal design; mortality; neural circuit; neurobiological mechanism; neurofeedback; neuroimaging; physical conditioning; post-traumatic symptoms; prediction algorithm; predictive modeling; prospective; rapid growth; response; reward circuitry; reward processing; social; social anxiety; social engagement; substance use; suicidal risk; therapy development; trauma exposure

Social withdrawal is a transdiagnostic phenotype that is strongly associated with detrimental physical and mental health outcomes across the lifespan. As quantified using structural features of individuals’ social networks, social withdrawal is associated with 60-70% increased mortality and a threefold increase in suicide risk. Recent findings document associations between trauma-related psychopathology and altered social network structural features, including size, density, diversity, and embeddedness. Critically, because the transition to adulthood (age 16-20) is a period of rapid expansion in social networks, forms of psychopathology that produce social withdrawal may confer particular risk for poor outcomes during this developmental stage. Thus, the transition to adulthood is a key developmental period for the evolution of social withdrawal in trauma- exposed populations. Recent literature indicates that social reward processing may drive social network size and complexity, but the role of disrupted social reward functioning in driving progressive social withdrawal following trauma exposure is poorly understood. Using an innovative longitudinal design including digital phenotyping of social behavior, the proposed study will investigate activity and connectivity within brain regions that bidirectionally code for social approach and avoidance, including the basolateral amygdala (BLA), ventromedial prefrontal cortex (VMPFC), and nucleus accumbens (NAcc). The hypothesis is that BLA-VMPFC- NAcc functional connectivity will prospectively predict progressive social withdrawal during the transition to adulthood following interpersonal trauma exposure. We will enroll 120 trauma-exposed participants (ages 16- 20) who endorse posttraumatic and/or depressive symptoms, and 60 healthy controls. Trauma-exposed participants will be stratified for baseline self-reported social anhedonia. We obtain baseline social withdrawal measures, including active self-reports of social interaction and passive smartphone based phenotyping of activity via accelerometer, GPS, and call/text metadata. Participants will complete an fMRI scan to obtain measures of BLA-VMPFC-NAcc connectivity, followed by one year of digital phenotyping using active and passive data to measure social withdrawal. Based on our extensive preliminary data, we hypothesize that: 1) baseline social withdrawal will be associated with baseline BLA-VMPFC-NAcc connectivity; (2) baseline BLA- VMPFC-NAcc connectivity will prospectively predict progressive social withdrawal over the course of a 12- month follow-up; (3) predictive models of social withdrawal that include BLA-VMPFC-NAcc connectivity will outperform alternate models. The proposed integrated approach (fMRI, digital phenotyping) will identify specific circuitry associated with progressive social withdrawal during the transition to adulthood, and will develop predictive algorithms that forecast social withdrawal trajectories based on baseline connectivity within BLA- VMPFC-NAcc circuitry. Ultimately this work could lead to the development of targeted interventions (e.g. neurofeedback), and may shift the field toward reward-circuitry accounts of social withdrawal.

社交退缩是一种转诊断表型，与有害的身体和行为密切相关。 心理健康的影响。使用个人社会结构特征进行量化 社交退缩与死亡率增加60-70%和自杀率增加三倍有关 风险最近的发现证明了创伤相关的精神病理学和改变的社会关系之间的联系。 网络结构特征，包括规模、密度、多样性和嵌入性。关键是，因为 过渡到成年期（16-20岁）是社交网络迅速扩张的时期， 在这一发展阶段，产生社会退缩可能会带来不良后果的特别风险。 因此，向成年的过渡是创伤中社会退缩演变的关键发展时期- 暴露人群。最近的文献表明，社会奖励处理可能会驱动社会网络的规模 和复杂性，但破坏社会奖励功能在推动渐进式社会退缩中的作用 创伤暴露后的情况知之甚少。采用创新的纵向设计， 社会行为的表型，拟议的研究将调查大脑区域内的活动和连接 包括基底外侧杏仁核（BLA）， 腹内侧前额叶皮质（VMPFC）和丘脑核（NAcc）。假设BLA-VMPFC- NAcc功能连接性将前瞻性地预测在过渡到 人际创伤暴露后的成年期我们将招募120名创伤暴露参与者（年龄16- 18岁）， 20)支持创伤后和/或抑郁症状的人，以及60名健康对照者。创伤暴露 参与者将根据基线自我报告的社交快感缺失进行分层。我们获得了基线社交退缩 措施，包括社会互动的主动自我报告和基于智能手机的被动表型分析， 通过加速度计、GPS和呼叫/文本元数据进行活动。参与者将完成fMRI扫描，以获得 BLA-VMPFC-NAcc连接性的测量，随后使用活性和 被动数据来衡量社交退缩。根据我们广泛的初步数据，我们假设：1） 基线社交退缩将与基线BLA-VMPFC-NAcc连接相关;（2）基线BLA- VMPFC-NAcc连接性将前瞻性地预测12- 14岁儿童的进行性社交退缩。 （3）包括BLA-VMPFC-NAcc连接的社交退缩预测模型将 优于其他型号。建议的综合方法（功能磁共振成像，数字表型） 将确定具体的 在向成年过渡期间，与渐进式社会退缩相关的电路，并将发展 基于BLA内的基线连接预测社交退缩轨迹的预测算法- VMPFC-NAcc电路。最终，这项工作可能导致制定有针对性的干预措施（例如， 神经反馈），并可能将该领域转向奖励电路帐户的社会退缩。