1/2 Neurodevelopmental and clinical trajectories of youth at risk for bipolar I disorder

1/2 有 I 型双相情感障碍风险的青少年的神经发育和临床轨迹

• 批准号: 10175841
• 负责人: Jorge R C Almeida
• 金额: $ 73.11万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10175841
• 关键词: 21 year old; Adolescence; Adult; Affective; Amygdaloid structure; Anxiety; Anxiety Disorders; Attention deficit hyperactivity disorder; Behavior; Behavioral; Bipolar Disorder; Bipolar I; Brain; Brain region; Characteristics; Child Abuse and Neglect; Clinical; Cognitive; Computer Models; Corpus striatum structure; Data; Development; Diffusion Magnetic Resonance Imaging; Disease; Early-life trauma; Emotional; Event; Exposure to; Failure; Family; Family history of; Feedback; Functional Magnetic Resonance Imaging; Funding; Future; General Population; Globus Pallidus; Goals; Heritability; Hypersensitivity; Image; Impairment; Individual; Inherited; Lead; Link; Longitudinal Studies; Machine Learning; Manic; Maps; Measures; Mediating; Mental Depression; Mental disorders; Mind; Moods; Motivation; Onset of illness; Outcome; Pathway interactions; Phenotype; Prefrontal Cortex; Principal Investigator; Recording of previous events; Recurrence; Reporting; Rewards; Risk; Risk Factors; Site; Structure; Subgroup; Substance Use Disorder; Suicide; Symptoms; Syndrome; System; Testing; Thalamic structure; Time; Unipolar Depression; Youth; austin; early life adversity; early life stress; emotion dysregulation; emotion regulation; experience; follow-up; mood symptom; prevent; programs; psychosocial; recruit; relating to nervous system; response; reward processing; substance misuse; suicidal behavior; young adult

Program Director/Principal Investigator (Last, First, Middle): Strakowski, Stephen M. ABSTRACT Although bipolar I disorder is a dynamic condition expressing a wide range of affective, cognitive and neurovegetative symptoms, it is defined by the occurrence of mania. Mania typically first emerges in adolescence and young adulthood, and it is a strongly predictive phenotype. Moreover, the early course of bipolar I disorder is progressive, as euthymic periods shorten over time. Additionally, bipolar I disorder is strongly familial with heritability rates approaching 85%. A family history of bipolar I disorder increases risk for mania as well as a number of other psychiatric conditions, including suicidal behaviors and reward hypersensitivity. Together, these characteristics suggest that bipolar I disorder results from an inherited failure during adolescence to develop healthy neural systems that modulate mood and behavioral activation. Complicating the inherited risk is that people with a family history of bipolar disorder also report higher rates of early life adversity than the general population. Early life adversity is associated with lifelong elevated rates of depression, anxiety and substance use disorders, impaired risk-reward processing, and suicide. Consequently, during development individuals with a familial risk for bipolar I disorder may be exposed to a dual risk, i.e. an inherited vulnerability and environmental early-life stress. How these risks interact to impact brain development and subsequent outcomes in these individuals is not known. Mood and risk-reward behaviors are managed by intersecting ventral prefrontal networks. These networks undergo substantial development in the transition from adolescence to young adulthood (when bipolar I disorder emerges) in which maturation of prefrontal networks leads to adaptive adult emotional regulation and risk-reward processing. Abnormalities in these networks are commonly described in both bipolar disorder and in response to early life adversity, with many shared characteristics. With these considerations in mind, we hypothesize that heritability for bipolar I disorder interacts with early life adversity to synergistically disrupt healthy ventral prefrontal network development during adolescence, underlying a cumulative increased risk for developing mania and other conditions more common in bipolar families. To test this hypothesis, over a four-year interval we will assess trajectories in ventral prefrontal network connectivity in youth at-familial-risk for bipolar I disorder compared to those without this risk, and the interaction with or without early life trauma, to determine whether these risks cumulatively lead to increasing emergence of: 1) mood symptoms and syndromes, 2) substance misuse, 3) suicidal behaviors, and 4) approach motivation hypersensitivity. These results can inform future approaches to prevent illness onset and progression in individuals at risk for or early in the course of bipolar disorder. OMB No. 0925-0001/0002 (Rev. 03/16 Approved Through 10/31/2018) Page Continuation Format Page

项目主任/首席调查员(最后、第一、中间)：斯特拉科夫斯基，斯蒂芬·M。 摘要 尽管双相I型障碍是一种动态状态，表现出广泛的情感、认知和 神经植物性症状，它的定义是躁狂的发生。躁狂症通常最先出现在 青春期和青春期，这是一个很强的预测性表型。此外，早期的过程中， 双相I型障碍是进行性的，因为欣快期随着时间的推移而缩短。此外，双相I型障碍 有很强的家族性，遗传率接近85%。I型双相情感障碍家族史增加风险 躁狂症以及其他一些精神疾病，包括自杀行为和奖励 过敏症。总而言之，这些特征表明双相I型障碍是由遗传性的 在青春期未能发展出调节情绪和行为激活的健康神经系统。 使遗传风险复杂化的是，有双相情感障碍家族史的人报告的发病率也更高 比一般人更容易遭受早年生活中的不幸。早年的逆境与终生的兴奋有关 抑郁、焦虑和物质使用障碍、风险回报处理受损和自杀的比率。 因此，在发育过程中，有双相情感障碍家族风险的个人可能会接触到 双重风险，即遗传脆弱性和环境早期应激。这些风险如何相互作用产生影响 这些人的大脑发育和随后的结果尚不清楚。 情绪和风险奖励行为是通过交叉的前额叶腹侧网络来管理的。这些 网络在从青春期到青壮年的过渡中经历了实质性的发展(当 出现双相I型障碍)，额叶前部网络成熟导致成人情绪适应 监管和风险回报处理。这些网络中的异常通常在这两个文件中描述 双相情感障碍和对早年逆境的反应，具有许多共同特征。有了这些 考虑到这一点，我们假设双相i型障碍的遗传性与早期的生活逆境相互作用。 协同干扰青春期健康的前额叶腹侧网络发育，潜在的 患躁狂症和其他在双相情感障碍家庭中更常见的疾病的累积风险增加。至 验证这一假设，我们将在四年的时间间隔内评估腹侧前额叶网络的轨迹 与没有这种风险的青少年相比，家庭中的青少年患双相情感障碍的风险更高， 有或没有早期生活创伤的相互作用，以确定这些风险是否累积导致 出现：1)情绪症状和症状，2)药物滥用，3)自杀行为，4) 接近动机过敏症。这些结果可以为未来预防疾病发作的方法提供参考 以及处于双相情感障碍风险中或病程早期的个体的进展。 OMB编号0925-0001/0002(03/16修订版批准至2018年10月31日)页面续格式页面