2/2-Neurodevelopmental and Clinical Trajectories of Youth at Risk for Bipolar Disorder

2/2-双相情感障碍风险青少年的神经发育和临床轨迹

• 批准号: 10459628
• 负责人: Melissa P Delbello
• 金额: $ 71.83万
• 依托单位: UNIVERSITY OF CINCINNATI
• 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/10459628
• 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; Persons; Phenotype; Prefrontal Cortex; Recording of previous events; Recurrence; Reporting; Rewards; Risk; Risk Factors; Site; 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; psychosocial; recruit; relating to nervous system; response; reward processing; substance misuse; suicidal behavior; young adult

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.

摘要 尽管双相I型障碍是一种动态疾病，表达了广泛的情感、认知和情感， 神经植物性症状，它的定义是躁狂症的发生。躁狂症通常首先出现在 青春期和青年期，它是一个强预测表型。此外，早期课程 I型双相情感障碍是进行性的，因为心境正常期随时间缩短。此外，双相I型障碍是 遗传率接近85%。双相I型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 超敏反应总之，这些特征表明双相I型障碍是遗传性的， 在青春期未能发展健康的神经系统，调节情绪和行为激活。 使遗传风险复杂化的是，有双相情感障碍家族史的人也报告了更高的发病率 比一般人更容易遭受早期生活的不幸早期生活中的逆境与终身的提升有关 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，具有双相I型障碍家族风险的个体可能暴露于 双重风险，即遗传的脆弱性和早年环境压力。这些风险如何相互影响 这些人的大脑发育和随后的结果尚不清楚。 情绪和风险-回报行为由交叉的腹侧前额叶网络管理。这些 网络在从青春期到青年期的过渡中经历了实质性的发展（当 出现双相I型障碍），其中前额叶网络的成熟导致适应性成人情绪 监管和风险回报处理。在这些网络中的abbands通常在两个 双相情感障碍和对早期生活逆境的反应，有许多共同的特征。与这些 考虑到这些因素，我们假设双相I型障碍的遗传性与早期生活逆境相互作用 在青春期协同破坏健康的腹侧前额叶网络发育， 躁狂症和其他在双相家族中更常见的疾病的累积风险增加。到 为了验证这一假设，我们将在四年的时间间隔内评估腹侧前额叶网络的轨迹 与没有这种风险的年轻人相比，有双相I型障碍家族风险的年轻人的连接性， 与或不与早期生活创伤的相互作用，以确定这些风险是否累积导致增加 出现：1）情绪症状和综合征，2）物质滥用，3）自杀行为，以及4） 接近动机超敏反应。这些结果可以为未来预防疾病发作的方法提供信息 以及处于双相情感障碍风险中或处于双相情感障碍早期过程中的个体的进展。