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: 9886839
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9886839
• 关键词: Accounting; Adult; Age; Aggressive behavior; Area; Behavioral; Behavioral Paradigm; Bipolar Disorder; Brain region; Chlorpromazine; Clinical; Clinical assessments; Cognitive; Complement; Emotional; Exanthema; Fiber; Functional Magnetic Resonance Imaging; Future; Healthcare; Image; Impulsive Behavior; Impulsivity; Individual; Inferior frontal gyrus; Interruption; Left; Lithium; Machine Learning; Major Depressive Disorder; Measures; Medical Records; Mental Health; Mental disorders; Modeling; Moods; Motor; Neurites; Neurobiology; Neurocognitive; Neuropsychology; Outcome Measure; Patient Self-Report; Patients; Persons; Phenotype; Post-Traumatic Stress Disorders; Psychotic Disorders; Recording of previous events; Rewards; Risk; Schizophrenia; Severities; Signal Transduction; Suicide; Suicide attempt; Testing; Ventral Striatum; Veterans; Work; base; 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; 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.

项目摘要 研究研究了资深人士的精神病与自杀之间关系的研究 事务表明，患有躁郁症的人的自杀率最高，这甚至更大 与创伤后应激障碍，精神分裂症和严重抑郁症相比。当未治疗时，双极 疾病自杀的死亡风险为5-15％，使其成为退伍军人精神卫生保健的重中之重。 双相情感障碍的人冲动地行为 - 即使在整齐时期 冲动性与双相情感障碍中自杀行为之间的关系可能有助于识别 未来自杀企图的风险最大的人。理解这种关系的进展一直是 然而，由于不同的冲动度度量的融合而显着阻碍了。冲动可以 使用自我报告措施或通过该状态测量作为相对稳定的特征测量 使用对不断变化的环境偶然性敏感的行为范式的使用。国家冲动模式 专注于（1）“快速响应抑制”，涉及困难的抑制反应 改变环境状况的背景和（2）“选择冲动”被定义为无法延迟 满足更大的奖励。这些模型与大脑区域的重叠较弱，但密切相关 在躁郁症的神经生物学中实施。我们提出调查状态和特征的措施 40名具有躁郁症（BD）和自杀企业历史（BD+S）的正式退伍军人的冲动性，40 具有躁郁症和无自杀尝试史（BD-S）和40个健康对照（HC）的福特退伍军人（HC）。 这项研究中的主要自杀结果指标将是使用哥伦比亚的自杀企图 自杀严重性评级量表和病历审查。这将通过使用 基于5种类型的自杀行为中的任何一种，更广泛的综合自杀结果指标 包括：（1）自杀死亡； （2）自杀企图； （3）自杀企图中断； （4）自杀未遂； 或（5）制备自杀行为。遵循全面的基线临床，神经心理学和 神经影像学评估所有退伍军人随后将完成6个月和12个月的亲身随访 情绪和自杀行为的临床评估。在这项研究中，对性状冲动的新颖测量将包括 紧迫性和冲动/有预谋的侵略性。我们将评估冲动激进的关系 BD+s中的社会认知，功能残疾和神经认知功能。我们将进一步调查 两个神经元电路利用快速响应抑制的状态测量（使用GO/No-Go任务）和选择 冲动性（分别使用延迟折现任务），使用功能磁共振成像和 神经取向分散和密度成像，这将提供纤维排列的新颖测量和 连接灰质区域的区域中的神经密度。动态因果建模将用于经验 测试因果模型，分别涉及完成这两个电路的大脑区域的相互作用。 机器学习将用于整合基线特征和冲动性的状态测量 预测一年内的自杀行为。这项研究的具体目的是：（1）调查关系 在患有躁郁症的退伍军人的冲动性和自杀企图历史之间的特质量度之间； （2）至 研究两种状态冲动模型的神经回路及其与自杀的关系 尝试患有躁郁症的退伍军人的历史； （3）确定冲动性措施的组合 在基线时间点将BD+S与BD-S和HC区分开，可用于预测自杀行为 纵向1年。