Predicting Suicidal Behavior in Veterans with Bipolar Disorder using Behavioral and Neuroimaging Based Impulsivity Phenotypes

使用基于行为和神经影像的冲动表型预测患有双相情感障碍的退伍军人的自杀行为

• 批准号: 10704555
• 负责人: PHILIP R SZESZKO
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10704555
• 关键词: Accounting; Adult; Age; Aggressive behavior; Area; Behavioral; Behavioral Paradigm; Bipolar Disorder; Brain region; Chlorpromazine; Clinical; Clinical assessments; Complement; Emotional; Exanthema; Fiber; Functional Magnetic Resonance Imaging; Future; Image; Impaired cognition; Impulsive Behavior; Impulsivity; Individual; Inferior frontal gyrus; Interruption; Left; Lithium; Machine Learning; Major Depressive Disorder; Measures; Medical Records; Meditation; Mental Health Services; Mental disorders; Modeling; Moods; Motor; Neurites; Neurobiology; Neurocognitive; Neuropsychology; Outcome Measure; Patient Self-Report; Patients; Persons; Phenotype; Population; Post-Traumatic Stress Disorders; Psychoses; Recording of previous events; Rewards; Risk; Schizophrenia; Severities; Signal Transduction; Suicide; Suicide attempt; Testing; United States Department of Veterans Affairs; Ventral Striatum; Veterans; Work; blood oxygen level dependent; causal model; density; discounting; environmental change; experience; follow-up; frontal lobe; functional disability; gray matter; mortality risk; negative affect; neural circuit; neuroimaging; novel; response; sex; social; social cognition; suicidal act; suicidal behavior; suicidal morbidity; suicide rate; trait; trait impulsivity; white matter

Project Summary Studies examining the relationship between psychiatric illness and suicide from the Department of Veterans Affairs indicate that individuals with bipolar disorder have the highest rate of suicide, which is even greater compared to post-traumatic stress disorder, schizophrenia and major depression. When left untreated, bipolar disorder has a 5-15% risk of death by suicide, making it a top priority for Veterans' mental health care. Individuals with bipolar disorder behave impulsively – even during euthymic periods and understanding the relationship between impulsivity and suicidal behavior in bipolar disorder may assist in the identification of individuals at greatest risk for a future suicide attempt. Progress in understanding this relationship has been significantly hampered, however, by the conflation of different measures of impulsivity. Impulsivity can be measured as a relatively stable trait using self-report measures or as a state measure assessed through the use of behavioral paradigms sensitive to changing environmental contingencies. Models of state impulsivity have focused on (1) “rapid-response inhibition” involving difficulty inhibiting responses that are prepotent in the context of changing environmental situations and (2) “choice impulsivity” defined as the inability to delay gratification for a larger reward. These models correlate weakly, but strongly overlap with brain regions implicated in the neurobiology of bipolar disorder. We propose investigating measures of state and trait impulsivity in 40 euthymic Veterans with bipolar disorder (BD) and a suicide attempt history (BD+S), 40 euthymic Veterans with bipolar disorder and no suicide attempt history (BD-S) and 40 healthy controls (HC). The primary suicide outcome measure in this study will be suicide attempts assessed using the Columbia Suicide Severity Rating Scale and medical record review. This will be complemented through the use of a broader composite suicide outcome measure based on the occurrence of any of 5 types of suicidal behavior including: (1) death by suicide; (2) suicide attempt; (3) interrupted suicide attempt; (4) aborted suicide attempt; or (5) preparatory suicidal acts. Following comprehensive baseline clinical, neuropsychological and neuroimaging assessments all Veterans will subsequently complete 6- and 12-month in-person follow-up clinical assessments of mood and suicidal behavior. Novel measures of trait impulsivity in this study will include urgency and impulsive/premeditated aggression. We will assess the relationship between impulsive aggression and social cognition, functional disability and neurocognitive functioning in BD+S. We will further investigate two neural circuits tapping state measures of rapid response inhibition (using a go/no-go task) and choice impulsivity (using a delay discounting task), respectively, using functional magnetic resonance imaging and neurite orientation dispersion and density imaging, which will provide novel measures of fiber arrangement and neurite density in tracts connecting gray matter regions. Dynamic causal modeling will be used to empirically test causal models regarding the interaction of brain regions comprising these two circuits respectively. Machine learning will be used to integrate baseline trait and state measures of impulsivity to longitudinally predict suicidal behavior over one year. The specific aims of this study are: (1) to investigate the relationship between trait measures of impulsivity and suicide attempt history in Veterans with bipolar disorder; (2) to investigate the neural circuitry underlying two models of state impulsivity and their relationship to suicide attempt history in Veterans with bipolar disorder; and (3) to identify which combination of impulsivity measures differentiates BD+S from BD-S and HC at a baseline timepoint and can be used to predict suicidal behavior longitudinally over 1 year.

项目概要 退伍军人部研究精神疾病与自杀之间的关系 事务表明，双相情感障碍患者的自杀率最高，甚至更高 与创伤后应激障碍、精神分裂症和重度抑郁症相比。如果不及时治疗，就会出现双相情感障碍 该疾病有 5-15% 的自杀风险，使其成为退伍军人心理保健的首要任务。 患有双相情感障碍的人即使在情绪正常且理解情绪正常的时期也会表现出冲动行为。 双相情感障碍的冲动和自杀行为之间的关系可能有助于识别 未来自杀企图风险最大的个人。对这种关系的理解取得了进展 然而，不同的冲动衡量标准的合并严重阻碍了这一过程。冲动可以是 使用自我报告测量作为相对稳定的特征进行测量，或通过评估作为状态测量 使用对不断变化的环境突发事件敏感的行为范式。国家冲动模型 重点关注（1）“快速反应抑制”，涉及难以抑制在 不断变化的环境情况的背景和（2）“选择冲动”定义为无法延迟 为获得更大的回报而感到满足。这些模型与大脑区域相关性较弱，但有很强的重叠 与双相情感障碍的神经生物学有关。我们建议研究状态和特质的测量 40 名患有躁郁症 (BD) 和自杀未遂史 (BD+S) 的情绪正常退伍军人的冲动，40 患有双相情感障碍且无自杀企图史的情绪正常退伍军人 (BD-S) 和 40 名健康对照者 (HC)。 本研究中主要的自杀结果衡量标准是使用哥伦比亚自杀倾向评估 自杀严重程度评定量表和医疗记录审查。这将通过使用 基于 5 种自杀行为中任何一种的发生的更广泛的综合自杀结果测量 包括： （一）自杀死亡； (2) 自杀未遂； (3) 自杀未遂； (4) 自杀未遂； (5) 准备自杀行为。遵循全面的基线临床、神经心理学和 神经影像评估 所有退伍军人随后将完成 6 个月和 12 个月的现场随访 情绪和自杀行为的临床评估。本研究中测量特质冲动的新方法将包括 紧迫感和冲动/有预谋的攻击行为。我们将评估冲动攻击之间的关系 BD+S 中的社会认知、功能障碍和神经认知功能。我们将进一步调查 两个神经回路利用快速反应抑制的状态测量（使用进行/不进行任务）和选择 冲动性（使用延迟贴现任务），分别使用功能磁共振成像和 神经突定向色散和密度成像，这将为纤维排列和密度成像提供新的测量方法 连接灰质区域的神经突密度。动态因果模型将用于实证 测试关于分别包含这两个回路的大脑区域相互作用的因果模型。 机器学习将用于纵向整合冲动性的基线特征和状态测量 预测一年内的自杀行为。本研究的具体目的是：（1）探讨两者之间的关系 患有双相情感障碍的退伍军人的冲动性特征测量与自杀企图历史之间的关系； (2) 至 研究两种状态冲动模型背后的神经回路及其与自杀的关系 患有双相情感障碍的退伍军人的尝试史； (3) 确定冲动措施的组合 在基线时间点区分 BD+S 与 BD-S 和 HC，可用于预测自杀行为 纵向超过1年。