Biological Risk Factors for the Prospective Development of Alcohol Use Disorders in Young Adults with Bipolar Disorder and Typically Developing Young Adults

患有躁郁症的年轻人和典型发育的年轻人未来发生酒精使用障碍的生物危险因素

• 批准号: 10583360
• 负责人: Elizabeth Thomas Cox Lippard
• 金额: $ 57.2万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-10 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583360
• 关键词: Acute; Address; Adolescence; Affect; Alcohol abuse; Alcohol consumption; Alcohols; Amygdaloid structure; Back; Biological; Bipolar Disorder; Child Abuse and Neglect; Clinical; Clinical Research; Cognitive deficits; Corpus striatum structure; Coupling; Data; Development; Diagnosis; Disease; Enrollment; Exclusion; Exposure to; Female; Fibrinogen; Funding; General Population; Goals; Human; Impulsivity; Individual; Insula of Reil; Intervention; Longitudinal Studies; Mentored Research Scientist Development Award; Methodology; Modeling; Moods; Outcome; Placebo Effect; Placebos; Population; Predictive Factor; Prevention; Procedures; Reporting; Research; Research Personnel; Research Project Grants; Risk; Risk Factors; Risk Marker; Risk Taking; Role; Stress; Structural Models; Structure; Substance Use Disorder; Symptoms; Testing; Time; Translating; Variant; Work; Youth; acute stress; aged; alcohol effect; alcohol misuse; alcohol response; alcohol risk; alcohol sensitivity; alcohol use disorder; clinical phenotype; clinical prognosis; comorbidity; early life stress; follow-up; functional MRI scan; functional loss; gray matter; improved; improved outcome; interest; multidisciplinary; multimodal neuroimaging; neural; neurodevelopment; neuroimaging; neurophysiology; novel; participant enrollment; preclinical study; predictive modeling; prospective; response; reward processing; stressor; suicide rate; white matter; young adult

Alcohol use disorders (AUDs) affect up to 60% of individuals with bipolar disorder during their lifetime and is associated with worse illness outcomes, yet few studies have been performed to clarify the causes of this comorbidity. Understanding biological risk factors that associate with and predict the development of AUDs in bipolar disorder could inform interventions and prevention efforts to reduce the rate of this comorbidity and improve outcomes of both disorders. Identifying predictors of risk requires longitudinal studies in bipolar disorder aimed at capturing the mechanisms leading to the emergence of AUDs. Previous work in AUDs suggest that subjective responses to alcohol and stress-related mechanisms may contribute to the development of AUDs. In bipolar disorder, altered developmental trajectory of critical ventral prefrontal networks that modulate mood and reward processing may alter responses to alcohol and stressors; consequently, the disruption in typical neurodevelopment may be an underlying factor for the high rates of comorbidity. No longitudinal data exist investigating if this developmental hypothesis is correct. To address this gap, we will use a multimodal neuroimaging approach, modeling structural and functional neural trajectories of corticolimbic networks over young adulthood, incorporating alcohol administration procedures, clinical phenotyping, and investigating effects of acute stress exposure and early life stress. Research aims are to identify biological risk factors—i.e., changes in subjective response to alcohol and associated neural trajectories—that are associated with the development of alcohol misuse and symptoms of AUDs over a two-year longitudinal period in young adults with bipolar disorder and typical developing young adults. Longitudinal data will be collected on 160 young adults (50% with bipolar disorder, 50% female; aged 21-26). This study is a natural extension of the PI's K01 award. How acute exposure to stress and childhood maltreatment affects subjective response to alcohol and risk for prospective alcohol misuse and symptoms of AUDs will be investigated. We will test our hypothesis that developmental differences in bipolar disorder versus typical developing individuals disrupt corticolimbic networks during young adulthood, increase sensitivity to stress, and lead to changes in subjective response to alcohol and placebo response increasing risk for developing AUDs. This research project will be conducted by a multidisciplinary team of investigators with expertise in bipolar disorder, AUDs, substance use disorders, stress, longitudinal modeling, neuroimaging, and alcohol administration methodology. Essential to successfully improving clinical prognosis in bipolar disorder are research results that enable better prediction, diagnosis, and treatment based on the individual. There is a paucity of human clinical research investigating interactions between subjective response to alcohol/placebo, corticolimbic development during the young adult epoch, and acute exposure to stress and childhood maltreatment. Findings may inform intervention efforts that are more specific and may serve as a model for improving life-long outcomes in bipolar disorder and typical developing youth.

酒精使用障碍（AUDs）影响高达60%的双相情感障碍患者， 与更糟糕的疾病结果相关，但很少有研究来阐明其原因。 科摩罗。了解与AUDs发展相关并预测AUDs发展的生物学风险因素， 双相情感障碍可以为干预和预防工作提供信息，以降低这种合并症的发生率， 改善这两种疾病的结果。确定风险预测因子需要双相情感障碍的纵向研究 旨在捕捉导致AUD出现的机制。以前在AUD方面的工作表明， 对酒精和压力相关机制的主观反应可能有助于AUD的发展。在 双相情感障碍，改变了调节情绪的关键腹侧前额叶网络的发展轨迹， 奖励处理可能会改变对酒精和压力的反应;因此，典型的 神经发育可能是高并发症发生率的潜在因素。无纵向数据 研究这个发展假说是否正确为了解决这个问题，我们将使用多模式 神经影像学方法，模拟皮质边缘网络的结构和功能神经轨迹， 青年期，包括酒精管理程序，临床表型，并调查影响 急性压力暴露和早期生活压力。研究的目的是确定生物风险因素，即，变化 在对酒精的主观反应和相关的神经冲动中， 年轻成人双相情感障碍患者两年纵向期间的酒精滥用和AUD症状 典型的发育中的年轻人。将收集160名年轻人的纵向数据（50%， 双相情感障碍，50%女性;年龄21-26岁）。本研究是PI K 01奖的自然延伸。有多敏锐 暴露于压力和儿童期虐待会影响对酒精的主观反应和未来的风险 将研究酒精滥用和AUD症状。我们将测试我们的假设， 双相情感障碍与典型发育个体的差异在年轻时破坏了皮质边缘网络 成年后，增加对压力的敏感性，并导致对酒精和安慰剂的主观反应发生变化 反应增加发展AUD的风险。该研究项目将由多学科 一组在双相情感障碍、AUD、物质使用障碍、压力、纵向 建模、神经成像和酒精给药方法学。成功改善临床 双相情感障碍预后的研究结果，使更好的预测，诊断和治疗的基础上， 对个人的影响缺乏人类临床研究，调查主观因素之间的相互作用。 对酒精/安慰剂的反应，年轻成人时期的皮质边缘发育，以及急性暴露于 压力和童年虐待。调查结果可以为更具体的干预措施提供信息， 作为改善双相情感障碍和典型发育中青年的终身结局的模型。