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.

在青少年中，重度抑郁障碍（MDD）和双相情感障碍（BD）占十大原因中的两个