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

项目总监/首席研究员（最后，第一，中间）：Strakowski，Stephen M. 抽象的 尽管双极I障碍是一种动态状况，表达了广泛的情感，认知和 神经性症状，它是由躁狂症的发生来定义的。躁狂通常首先出现 青春期和成年年轻，这是一种强烈的预测表型。而且，早期的课程 随着时间的流逝，躁郁症疾病是渐进的，随着正常时期的缩短。此外，双相情感障碍是 遗传力率的强烈家族性接近85％。双相情感障碍的家族史增加了风险 对于躁狂以及许多其他精神病疾病，包括自杀行为和奖励 高敏性。这些特征共同表明，双极I障碍是由遗传的 青春期失败，无法开发健康的神经系统，以调节情绪和行为激活。 使继承的风险复杂化的是，患有躁郁症家族史的人也报告了更高的率 早期逆境比一般人群的逆境。早期逆境与终生升高有关 抑郁症，焦虑和药物使用障碍的率，风险奖励的处理受损和自杀。 因此，在发育过程中，患有躁郁症疾病的家族风险的人可能会暴露于 双重风险，即继承的脆弱性和环境早期压力。这些风险如何相互作用以影响 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相交腹前额叶网络来管理的。这些 网络在从青春期到成年的过渡中经历了重大发展（当 出现双极I障碍），其中前额叶网络的成熟导致适应性成人情绪 监管和风险奖励处理。这些网络中的异常都在两者中通常描述 双相情感障碍和对早期生命逆境的反应，具有许多共同特征。与这些 考虑到这一点，我们假设双相情感障碍的遗传力与早期逆境相互作用 在青春期中协同破坏健康的腹侧前额叶网络的发展 累积增加了躁狂和其他疾病在双极家庭中更常见的风险。到 检验该假设，在四年间，我们将评估腹侧前额叶网络中的轨迹 与没有这种风险的人相比 有或没有早期生命创伤的互动，以确定这些风险是否会导致增加 出现：1）情绪症状和综合征，2）滥用物质，3）自杀行为和4） 接近动机超敏反应。这些结果可以为预防疾病发作的未来方法提供信息 在双相情感障碍过程中有或早期有风险或早期的个体进展。 OMB编号0925-0001/0002（Rev. 03/16批准通过10/31/2018）页面延续格式页面