Neurobiological markers of risk and resilience for psychopathology in youth at familial risk for mood disorders

具有情绪障碍家族风险的青少年精神病理学风险和复原力的神经生物学标记

• 批准号: 10534068
• 负责人: Bailey Holt-Gosselin
• 金额: $ 4.68万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10534068
• 关键词: Adolescence; Adolescent; Amygdaloid structure; Anterior; Base of the Brain; Biological; Biological Markers; Bipolar Disorder; Brain; Brain region; Categories; Child; Clinical; Corpus striatum structure; Data; Detection; Development; Dimensions; Disease; Dorsal; Early Diagnosis; Early Intervention; Emotions; Exhibits; Family history of; Funding; Human; Intervention; Investigation; Knowledge; Lateral; Major Depressive Disorder; Measurement; Medial; Mental Health; Mental disorders; Mentorship; Modeling; Mood Disorders; National Research Service Awards; Neurobiology; Outcome; Pattern; Prefrontal Cortex; Psychopathology; Recording of previous events; Research; Rest; Rewards; Risk; Risk Marker; Sample Size; Seeds; Severities; Statistical Models; Symptoms; Time; Training; United States National Institutes of Health; Ventral Striatum; Youth; base; career; clinical diagnosis; cognitive development; design; disability; disorder risk; early onset; improved; ineffective therapies; insight; interest; intervention program; longitudinal course; longitudinal dataset; multidisciplinary; neural circuit; neurobiological mechanism; neuroimaging; neuromechanism; predictive marker; psychiatric symptom; recruit; relating to nervous system; resilience; suicidal risk

Among youth, major depressive disorder (MDD) and bipolar disorder (BD) represent two of the top ten causes of disability and confer heightened risk of suicide. Since BD often initially presents as a MDD episode, youth with BD are frequently misdiagnosed and thus receive ineffective treatment. Family history of mood disorders is a robust predictor of early-onset MDD and BD as well as other psychiatric disorders. Prior studies have identified neurobiological differences between healthy youth at high familial risk for BD or MDD relative to low familial risk, and one study has identified neural circuit differences between youth at high familial risk for BD versus MDD. Relatedly, there is preliminary evidence for neural markers that predict later onset of psychopathology among youth at high familial risk for BD and MDD. These studies suggest that there are markers of vulnerability that can be detected in the brain, prior to symptom onset, which may further increase risk for poor mental health outcomes among these susceptible youth. However, extant research has been limited by small sample sizes and a lack of multiple longitudinal symptom measurements over time, which have hindered the identification of robust biomarkers that distinguish risk profiles among youth with a family history of BD versus MDD. The identification of brain-based signatures of BD and MDD risk in youth would advance understanding of distinct mechanisms underlying heightened vulnerability, which may ultimately inform approaches for earlier and more accurate identification of these disorders. The present study aims to uncover unique neurobiological profiles of high familial risk for BD and MDD among healthy youth, and to investigate whether these biomarkers predict the subsequent onset and longitudinal course of psychopathology across adolescence. This study will include healthy youth at low (LR, n=3,915) or high familial risk for MDD (HR-MDD, n=1,564) or BD (HR-BD, n=407) with longitudinal data up to 3 years, derived from the landmark Adolescent Brain Cognitive Development (ABCD) Study. Aim 1 will examine dissociable patterns of resting-state functional connectivity (FC) in emotion- and reward-related networks at baseline between healthy HR-BD, HR-MDD, and LR youth, using a whole-brain seed- to-voxel approach with the amygdala, ventral striatum, and dorsal striatum as seed regions of interest. Aim 2 will ascertain longitudinal trajectories of dimensional psychiatric symptoms across adolescence over 3 years in high familial risk youth using group-based trajectory modeling. Aim 3 will investigate whether alterations in baseline FC within emotion- and reward-related networks predicts the presence of a clinical diagnosis in later adolescence and/or a more severe longitudinal course of dimensional symptoms across adolescence. This research will reveal critical insight into the mechanisms that contribute to risk versus resilience in vulnerable youth, potentially serving as key biological targets for interventions. This knowledge may also potentially inform early detection and intervention programs, which will help to alleviate the immense burden of BD and MDD.

在年轻人中，主要抑郁症（MDD）和躁郁症（BD）代表了十大原因中的两个 残疾和自杀风险增加。由于BD最初经常以MDD的形式出现，因此 BD经常被误诊，因此接受无效治疗。情绪障碍的家族史是 早期发作的MDD和BD以及其他精神疾病的强大预测指标。先前的研究已经确定 相对于低家族风险，健康的青年在高家族风险或MDD的高家族风险的健康青年之间存在神经生物学差异， 一项研究确定了BD与MDD高家族风险的青年之间的神经回路差异。 相关的是，有初步证据证明神经标记物可以预测以后的心理病理学发作 BD和MDD的家族风险高的年轻人。这些研究表明，有一些脆弱性的标志 可以在症状发作之前在大脑中检测到，这可能会进一步增加心理健康不良的风险 这些易感青年的结果。但是，现有的研究受到小样本量的限制 并且随着时间的流逝缺乏多次纵向症状测量，这阻碍了识别 强大的生物标志物，区分BD与MDD家族史的年轻人之间的风险概况。这 在青年中识别BD和MDD风险的基于大脑的签名将提高对不同的理解 脆弱性增强的机制，这可能最终为早期的方法提供信息 这些疾病的准确识别。本研究旨在发现独特的神经生物学特征 健康青年中BD和MDD的高家族风险，并调查这些生物标志物是否预测 随后在青春期的心理病理学的发作和纵向过程。这项研究将包括 MDD（HR-MDD，n = 1,564）或BD（HR-BD，hr-bd，n = 407）的健康青年（LR，n = 3,915）或高家族风险 纵向数据长达3年，源自具有里程碑意义的青少年脑认知发展（ABCD） 学习。 AIM 1将检查情感和情感 - 和 使用全脑种子 - 与杏仁核，腹侧纹状体和背侧纹状体作为感兴趣的种子区域的木毒物接近。目标2 将在3年内确定整个青春期的纵向精神症状的纵向轨迹 使用基于群体的轨迹建模的高家族风险青年。 AIM 3将调查是否改变 情绪和奖励相关的网络中的基线FC预测稍后的临床诊断 青春期和/或更严重的纵向纵向症状的纵向症状。这 研究将揭示对有助于风险与弹性弹性的机制的关键见解 青年，可能是干预措施的关键生物学靶标。这些知识也可能会告知 早期检测和干预计划将有助于减轻BD和MDD的巨大负担。