Visceral neural circuits linking childhood threat and deprivation with stress physiology and affective symptoms in a transdiagnostic sample using high-field personalized brain mapping

使用高场个性化大脑映射在跨诊断样本中将童年威胁和剥夺与应激生理学和情感症状联系起来的内脏神经回路

• 批准号: 9980497
• 负责人: Layla Banihashemi
• 金额: $ 43.74万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-19 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980497
• 关键词: Affective; Affective Symptoms; Age; Amygdaloid structure; Anterior; Anxiety; Brain; Brain Mapping; Brain Stem; Brain region; Catecholamines; Cell Nucleus; Child Abuse; Childhood; Chronic stress; Clinical; Communities; Data; Distal; Dropout; Emotional; Emotions; Face; Fright; Glucocorticoids; Hair; Hippocampus (Brain); Hydrocortisone; Hypothalamic structure; Individual; Individual Differences; Intervention; Link; Literature; Magnetic Resonance Imaging; Maps; Measures; Mediating; Mental Health; Mental disorders; Methodology; Modeling; Mood Disorders; Moods; National Institute of Mental Health; Neighborhoods; Noise; Nucleus solitarius; Outcome; Pathway interactions; Phase; Physiological; Physiology; Pre-Clinical Model; Prosencephalon; Psyche structure; Psychiatry; Psychopathology; Public Health; Research; Research Domain Criteria; Resolution; Rest; Risk Factors; Salivary; Sampling; Severities; Sexual abuse; Signal Transduction; Socioeconomic Status; Stimulus; Stress; Structure; Structure of terminal stria nuclei of preoptic region; Thinking; Translating; Trauma; Visceral; base; biological adaptation to stress; childhood adversity; cingulate cortex; connectome; deprivation; environmental stressor; excitotoxicity; experience; improved; interest; low socioeconomic status; multimodality; neural circuit; neuroimaging; novel; paraventricular nucleus; physical abuse; physical conditioning; recruit; relating to nervous system; response; stress reactivity; traumatic event; ultra high resolution; urinary; white matter; young adult

Project Summary/Abstract Childhood adversity was recently posited to be psychiatry's greatest public health challenge, as it is a major predictor of mood, anxiety and trauma-related (i.e., affective) disorders. Childhood adversity is also associated with dysregulated physiological stress reactivity, which individuals with affective disorders also display. While stress is thought to be a mechanism by which childhood adversity influences physical and mental health, few studies have considered stress-related brain regions beyond corticoamygdalar and hippocampal structures and little is known regarding how childhood adversity impacts specific, proximally stress-responsive neural circuits. Central visceral circuits (CVCs) are implicated in affective psychopathology and are critical in the control of stress responses. CVCs comprise visceromotor and viscerosensory pathways that reciprocally connect hypothalamic and limbic forebrain regions to brainstem nuclei. Preliminary data show significant links between: 1) childhood adversity and CVCs and 2) CVCs and affective symptoms. These results also suggest opposing influences of childhood “threat” vs. “deprivation” on CVCs. “Threat” experiences include abuse and other traumatic events, while “deprivation” comprises diminished environmental stimuli, such as low childhood socioeconomic status or neighborhood deprivation. Interestingly, evidence suggests that threat blunts, while deprivation heightens physiological stress reactivity (e.g., cortisol reactivity). Thus, we propose that threat and deprivation may have different effects on the CVCs most proximal to the control of stress responses, including understudied regions such as the brainstem nucleus of the solitary tract (NST), paraventricular nucleus of the hypothalamus (PVN) and bed nucleus of the stria terminalis (BST). In the proposed, limitations of lower field strength MRI are overcome with the improved signal-to-noise and unprecedented resolution of high-field MRI at 7 Tesla. Multimodal neuroimaging will acquire specialized structurals, and resting-state, mental stress and emotion-evoked, and white matter connectivity. Stress physiology measures will also be collected. Consistent with the RDoC initiative, we will recruit a continuous and transdiagnostic community sample of 220 young adults (ages 18-35) with a full range of childhood threat, deprivation and affective symptoms to examine: 1) the effects of childhood threat and deprivation on CVC connectivity, 2) the effects of childhood threat and deprivation on stress physiology and affective symptoms, and 3) the extent to which CVC connectivity mediates the relationship between threat and deprivation, and physiological and affective outcomes. Significance. Our proposal is congruent with NIMH Strategy 1.3, Map the connectomes for mental illnesses, focusing on CVCs as the “connectome” of interest. Elucidating how CVCs may link childhood threat and deprivation to stress physiology and affective symptoms using high-field personalized brain mapping may enhance our ability to translate findings from preclinical models and may guide clinical thinking by providing novel proximally stress-responsive targets and/or novel or integrative approaches for intervention.

项目总结/摘要 儿童期的逆境最近被认为是精神病学最大的公共卫生挑战，因为它是一个主要的 情绪、焦虑和创伤相关的预测因子（即，情感）障碍。童年的不幸也与 生理应激反应失调，情感障碍患者也表现出这种情况。而 压力被认为是童年逆境影响身心健康的一种机制， 研究认为，除了皮质杏仁核和海马结构之外， 关于童年逆境如何影响特定的近端压力反应神经元， 电路.中枢内脏回路（CVC）与情感性精神病理学有关，并且在情感性精神病理学中至关重要。 控制压力反应。CVC包括内脏和内脏感觉通路， 将下丘脑和边缘前脑区域连接到脑干核团。初步数据显示 1）童年逆境与CVC和2）CVC与情感症状之间的关系。这些结果还表明 儿童期“威胁”与“剥夺”对CVC的影响相反。“威胁”经历包括虐待和 其他创伤事件，而“剥夺”包括减少环境刺激，如低童年， 社会经济地位或邻里剥夺。有趣的是，有证据表明，威胁减弱，而 剥夺增强了生理应激反应（例如，皮质醇反应性）。因此，我们建议， 剥夺可能对最接近应激反应控制的CVC产生不同的影响，包括 研究不足的区域，如脑干孤束核（NST），室旁核， 下丘脑室旁核（PVN）和终纹床核（BST）。在建议中，低场的局限性 高场强MRI的信噪比提高，分辨率前所未有， 7特斯拉多模态神经成像将获得专门的结构，和休息状态，精神压力和 情绪诱发和白色物质连接。还将收集应激生理学指标。一致 通过RDoC倡议，我们将招募220名年轻人作为连续的跨诊断社区样本， 成年人（18-35岁）与全方位的儿童威胁，剥夺和情感症状检查：1） 儿童期威胁和剥夺对CVC连接的影响，2）儿童期威胁和剥夺对CVC连接的影响 剥夺对应激生理和情感症状的影响，以及3）CVC连接的程度 中介威胁和剥夺之间的关系，生理和情感的结果。 意义我们的建议与NIMH策略1.3一致，绘制精神疾病的连接体， 关注CVC作为感兴趣的“连接体”。阐明CVC如何将儿童期威胁与 使用高场个性化脑映射的压力生理和情感症状的剥夺可以 提高我们从临床前模型中转化发现的能力，并通过提供 新的近端应激反应靶点和/或新的或综合的干预方法。