Neurobiological Underpinnings of Two Suicidal Subtypes

两种自杀亚型的神经生物学基础

• 批准号: 9272942
• 负责人: Maria A Oquendo
• 金额: $ 48.81万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-15 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9272942
• 关键词: Affect; Aggressive behavior; Agonist; American; Antidepressive Agents; Behavioral; Biological; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chronic; Clinical; Clinical assessments; Cognitive; Complex; Cost Savings; Cross-Sectional Studies; Data; Data Set; Depressed mood; Ecological momentary assessment; Emotional; Enrollment; Event; Feeling suicidal; Functional Magnetic Resonance Imaging; Future; General Population; Hydrocortisone; Image; Impulsivity; Individual; Intervention; Laboratories; Life; Link; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Mediating; Mental Depression; Mental disorders; Methods; Modality; Modeling; National Institute of Mental Health; Neurobiology; Neurocognitive; Outcome; Outcome Measure; Pattern; Pharmacology; Phenotype; Positron-Emission Tomography; Prefrontal Cortex; Prospective Studies; Psychosocial Stress; Recording of previous events; Recruitment Activity; Regulation; Reporting; Research; Risk; Risk Factors; Sampling; Savings; Strategic Planning; Stress; Subgroup; Suicide; Suicide attempt; Task Performances; Testing; Time; Trauma; Trier Social Stress Test; Violence; biological adaptation to stress; clinical risk; cognitive control; cohort; depressed patient; design; dorsal raphe nucleus; emotion regulation; environmental stressor; experience; follow up assessment; follow-up; high risk; improved; innovation; multimodality; pediatric trauma; prospective; psychologic; public health relevance; response; stressor; suicidal; suicidal behavior; suicidal morbidity; suicide attempter; suicide rate

 DESCRIPTION (provided by applicant): In 2011, 41,146 Americans died by suicide, surpassing the alarming 2010 toll of 38,364. Suicidal behavior (SB) (deaths/attempts) is linked to neurobiological, neurocognitive and behavioral factors, but integrative, multimodal studies are rare. Often, prospective studies, crucial to understanding future risk, have focused on single predictors and a single outcome, implying that SB is homogeneous. Yet, SB is complex and heterogeneous: it can be impulsive or methodically planned; violent or not, reactive to life events or occur despite no obvious stressors suggesting different subtypes. As a first step towards disentangling these subtypes, our model, supported by our pilot data, posits 2 putative phenotypes of SB associated with different patterns of suicidal ideation (SI). We have identified a variable pattern of suicidal ideation typically occurring in individuals with a trauma history wh react to environmental stressors with aggression, pronounced cortisol response and variable SI, in part due to difficulty engaging prefrontal regions in affect regulation. In contrast, we posit tat when SI is elevated but with little fluctuation, it is linked to blunted serotonergic function, and greater cognitive control leading to more planned and lethal SB. The Conte Center (CC) P50-MH090964, conducts cross-sectional studies of SB in Major Depression. We seek to follow this cohort and a newly enrolled sample of depressed patients for 2 years, the highest risk period. Baseline CC assessments mean significant cost savings and maximize use of a rich dataset including: Point-Subtraction Aggression Paradigm for RA, PET imaging with our new agonist, [11C]CUMI-101 to quantify 5-HT1A BPF, and a cognitive emotion regulation task in the MRI scanner. We will administer Stroop and Continuous Performance Tasks to assess cognitive control and prospectively quantify SI and SB, life events and depression using clinical and Ecological Momentary Assessments (EMA). Key innovations are: (1) prospective, multi-modal design to (2) delineate 2 distinct SB subtypes, which may yield more robust predictors; (3) assessment of emotion regulation which may predict SI and SB; (4) use of EMA to delineate origins of SI in real time; (5) Laboratory assessments to characterize trajectories of suicidal subgroups. Impact: In large general population samples, most suicide attempters report SI (NESARC [94.2%]; NLAES [86.8%]), yet >50% of suicides had no prior SB. Thus, prior SB is limited as a predictor of future SB, especially suicide death, so better understanding of SI is crucial to improving prediction and understanding of SB. Critically, if variable SI is a harbinger f impulsive suicide attempts, then delineation of distinct biological and clinical features associate with it or not, may help delineate different risk patterns. Ultimately, it may aid in prospectively identifying those at risk for different expressions/phenotypes of SB. Moreover, future studies could examine the merits of pharmacologic or psychological interventions targeting affect regulation for variable SI, versus antidepressants or cognitive treatments for sustained SI.

 2011年，41，146名美国人死于自杀，超过了2010年令人震惊的38，364人。自杀行为（SB）（死亡/企图）与神经生物学、神经认知和行为因素有关，但综合性、多模式研究很少。通常情况下，前瞻性研究，了解未来的风险至关重要，集中在单一的预测因素和单一的结果，这意味着SB是同质的。然而，SB是复杂和异质的：它可以是冲动的或有条不紊的计划;暴力或不暴力，对生活事件的反应 或者在没有明显压力源的情况下发生，表明不同的亚型。作为解开这些亚型的第一步，我们的模型，由我们的试点数据支持，假定2个推定的SB表型与不同模式的自杀意念（SI）。我们已经确定了一种可变的自杀意念模式，通常发生在有创伤史的个体中，这些个体对环境压力源的反应包括攻击性、明显的皮质醇反应和可变的SI，部分原因是难以使前额区参与情感调节。相反，我们认为当SI升高但波动很小时，它与β-肾上腺素能功能减弱有关， 更大的认知控制导致更多的计划和致命的SB。康特中心（CC）P50-MH 090964，进行了严重抑郁症SB的横断面研究。我们试图跟踪这个队列和一个新入组的抑郁症患者样本2年，这是最高风险期。基线CC评估意味着显著的成本节约和最大限度地利用丰富的数据集，包括：RA的点减攻击范式，使用我们的新激动剂的PET成像，[11 C] TBI-101量化5-HT 1A BPF，以及MRI扫描仪中的认知情绪调节任务。我们将管理Stroop和持续表现任务，以评估认知控制，并使用临床和生态瞬时评估（EMA）前瞻性量化SI和SB，生活事件和抑郁。主要创新包括：（1）前瞻性多模态设计，以（2）描述2种不同的SB亚型，这可能产生更可靠的预测因子;（3）评估情绪调节，这可能预测SI和SB;（4）使用EMA描述真实的时间SI的起源;（5）实验室评估，以表征自杀亚组的轨迹。影响：在大量的一般人群样本中，大多数自杀者报告SI（NESARC [94.2%]; NLAES [86.8%]），但>50%的自杀者没有先前的SB。因此，先前的SB作为未来SB，特别是自杀死亡的预测因子是有限的，因此更好地理解SI对于提高SB的预测和理解至关重要。那么描述与之相关或不相关的不同的生物学和临床特征可能有助于描述不同的风险模式。最终，它可能有助于未来 此外，未来的研究可以检查药理学或心理干预的优点，针对变量SI的影响调节，与抗抑郁药或认知治疗持续SI。