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

社交退缩是一种跨诊断表型，与有害的身体和精神疾病密切相关 一生中的心理健康结果。如使用个体社会的结构特征进行量化 在社交网络中，社交退缩会导致死亡率增加60%-70%，自杀率增加三倍 风险。最近的发现记录了创伤相关的精神病理学和社会变化之间的联系 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(16-20岁)是社会网络、精神病理学形式的快速扩张期 在这一发展阶段，产生社会退缩可能会带来特别的风险，导致不良结果。 因此，成年期是创伤中社会退缩演变的关键发展时期-- 暴露的人群。最近的文献表明，社交奖励处理可能会推动社交网络的规模 和复杂性，但扰乱的社会奖励功能在推动渐进性社会退缩中的作用 创伤暴露后，人们对此知之甚少。使用创新的纵向设计，包括数字 社交行为的表型，这项拟议的研究将调查大脑区域内的活动和连接 这种双向编码用于社交接近和回避，包括基底外侧杏仁核(BLA)， 腹内侧额前皮质(VMPFC)和伏隔核(NAcc)。假设是BLA-VMPFC- NACC功能连接将预测在过渡到 在人际关系创伤暴露后的成年期。我们将招募120名创伤暴露的参与者(16岁- 20)支持创伤后和/或抑郁症状的人，以及60名健康对照。创伤--暴露 参与者将根据基线自我报告的社交快感缺乏症进行分层。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 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 测量BLA-VMPFC-NAcc的连接性，然后使用Active和NAcc进行一年的数字表型 衡量社交退缩的被动数据。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连接将前瞻性地预测在12- 一个月的随访；(3)包括BLA-VMPFC-NAcc连接的社交退缩预测模型将 表现优于其他型号。建议的综合方法(功能磁共振成像、数字表型) 将确定具体的 在向成年过渡的过程中，与渐进性社会退缩相关的回路，并将发展 基于BLA内的基线连接性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)，并可能将研究领域转向社交退缩的奖励电路账户。

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.