Childhood adversity and central visceral circuits: mechanisms of affective risk

描述（由申请人提供）：童年逆境是发展复发性和慢性情绪和焦虑症的风险因素。此外，童年逆境与失调的压力反应有关，这也是情绪和焦虑症的基础。然而，童年逆境塑造压力反应和赋予压力相关的情感障碍的脆弱性的机制尚不清楚。中枢内脏回路（CVC）包括一个候选的神经机制，可能是压力反应失调和情感障碍的基础。这些回路是脑-体连接的神经基础，负责情感和生理之间的相互关系以及压力反应的控制。CVC包括协调生理流出的下行前自主神经回路，以及将有关身体状态的信息从脑干传递到高阶脑区的上行内脏感觉回路。早期生活经历对CVC的结构和功能有不同的影响，这一点在大鼠中的研究中得到了证实。虽然童年的逆境与总的变化有关（例如，在人类与情绪相关的大脑区域和神经束中，关于童年逆境如何具体影响CVC，我们知之甚少。为了验证中心假设，即童年逆境通过CVC结构和功能的变化影响后来的压力反应和对情感障碍的脆弱性，将在120名年轻成年人的代表性社区样本中评估三个目标。这些参与者将被很好地描述为童年逆境（例如，情感和身体虐待或忽视，父母争吵）和情感障碍症状（即，抑郁和焦虑症状）。参与者将完成一个MRI扫描仪会议，以获得多模态神经成像数据，包括：1。高分辨率结构连通性（来自扩散光谱成像序列和随后的详细纤维束成像的措施），2。结构完整性（从扩散张量成像序列导出的测量值），以及3.应激诱发的功能连接（用血氧水平依赖性时间序列数据进行的心理生理学相互作用分析）。目的1测试的假设，童年逆境将与CVC的结构和功能的连接。目的2测试的假设，童年逆境将与压力反应（来自MRI扫描仪内获得的心理生理数据）和情感障碍症状。目的3（探索性）测试CVC结构/功能在多大程度上代表了童年逆境和压力反应或情感障碍症状之间的路径的一部分。重要性：发现CVC结构和功能的不良相关变化有可能提供早期检测情感障碍风险和评估干预措施治疗情感障碍的有效性的方法。

DESCRIPTION (provided by applicant): Childhood adversity is a risk factor for developing recurrent and chronic mood and anxiety disorders. Further, childhood adversity is associated with dysregulated stress reactivity, which also underlies mood and anxiety disorders. However, the mechanisms by which childhood adversity shapes stress reactivity and confers vulnerability to stress-related affective disorders are unclear. Central visceral circuits (CVCs) comprise a candidate neural mechanism that may underlie both dysregulated stress reactivity and affective disorders. These circuits are the neural basis of brain-body connections, and are responsible for the reciprocal relationship between affect and physiology and the control of stress responses. CVCs encompass descending preautonomic circuits that orchestrate physiological outflow, and ascending viscerosensory circuits that relay information regarding body state from the brainstem to higher order brain areas. Early life experience differentially influences the structure and function of CVCs, as evidenced by studies in rat. While childhood adversity is associated with gross variations (e.g., in volume) within emotion-related brain regions and tracts in humans, littl is known regarding how childhood adversity specifically influences CVCs. To test the central hypothesis that childhood adversity influences later stress reactivity and vulnerability to affectie disorders via changes in the structure and function of CVCs, three aims will be evaluated in a representative community sample of 120 young adults. These participants will be well characterized for childhood adversity (e.g., emotional and physical abuse or neglect, parental arguing) and affective disorder symptoms (i.e., depressive and anxious symptoms). Participants will complete one MRI scanner session in order to gain multimodal neuroimaging data, including: 1. High-resolution structural connectivity (measures derived from a diffusion spectrum imaging sequence and subsequent detailed tractography), 2. Structural integrity (measures derived from a diffusion tensor imaging sequence), and 3. Stressor-evoked functional connectivity (psychophysiological interaction analyses performed with blood-oxygen-level dependent time-series data). Aim 1 tests the hypothesis that childhood adversity will be associated with the structural and functional connectivity of CVCs. Aim 2 tests the hypothesis that childhood adversity will be associated with both stress reactivity (derived from psychophysiological data acquired within the MRI scanner) and affective disorder symptoms. Aim 3 (Exploratory) tests the extent to which CVC structure/function represents a part of the path between childhood adversity and stress reactivity or affective disorder symptoms. Significance: Uncovering adversity-related changes in the structure and function of CVCs has the potential to provide methods of early detection of risk for affective disorders and of assessing the effectiveness of interventions in treating affective disorders.