Positive and Negative Valence Systems Underlying Suicide in Youth

青少年自杀背后的正价和负价系统

• 批准号: 9892475
• 负责人: Vilma Gabbay
• 金额: $ 46.14万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-10 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892475
• 关键词: Acute; Address; Adolescent; Adult; Age; Anatomy; Anhedonia; Anxiety; Biological Markers; Brain; Cause of Death; Cessation of life; Clinical; Cohort Studies; Corpus striatum structure; Data; Depressed mood; Diagnosis; Disease; Dorsal; Exhibits; Functional Magnetic Resonance Imaging; Future; Gambling; Goals; Habenula; Handedness; Hyperactive behavior; Individual; Insula of Reil; Knowledge; Link; Magnetic Resonance Imaging; Maps; Matched Group; Measurable; Mental Depression; Modeling; Negative Valence; Neurobiology; Nucleus Accumbens; Outcome; Pain; Play; Positive Valence; Process; Public Health; Recording of previous events; Resolution; Rest; Rewards; Risk; Risk Factors; Role; Signal Transduction; Structure; Subgroup; Suicide; Suicide attempt; Symptoms; System; Testing; Time; Ventral Tegmental Area; Work; Youth; accomplished suicide; age group; behavior measurement; behavioral construct; biobehavior; child depression; cohort; computerized; depressive symptoms; experience; indexing; machine learning algorithm; mortality; neuroimaging; neuronal circuitry; novel; pleasure; psychiatric symptom; relating to nervous system; research clinical testing; response; reward anticipation; reward circuitry; reward expectancy; sensory cortex; sex; suicidal; suicidal adolescent; suicidal behavior; suicidal risk; suicide rate

PROJECT SUMMARY/ABSTRACT Suicide is a major public health concern in adolescents and the second leading cause of death in this age group, highlighting the need to investigate suicide in adolescents. The two most prominent risk factors for completed suicide in youth are a past suicide attempt and a diagnosis of a depressive episode, each independently representing a 10- to 30-fold increased risk for completed suicide. However, while over 80% of suicidal youth present with depressive symptoms at the time of the attempt, only 30% of depressed youth will ever attempt suicide. These data suggest that depressed adolescents with prior suicide attempts represent a distinct neurobiological subgroup. However, at present, we have no biomarkers to identify those depressed youth who will engage in suicidal behavior. This proposal addresses this concern. Our proposed model is: (1) anhedonia is associated with heightened suicidal risk in depressed youth; (2) both positive valence (PVS) deficits (reward expectancy, attainment, positive prediction error) and negative valence (NVS) hyperactivity (negative prediction error, pain avoidance) contribute to anhedonia and underlie suicidal behavior in depressed youth; (3) the habenula (Hb), a small limbic hub, plays a key role in PVS/NVS processes by inhibiting reward signaling in response to pain and loss; and (4) recent advances in high-resolution MRI address prior technical constraints in studying small structures such as the Hb. These advances now allow us to study the neuronal circuitry underlying PVS and NVS in a neuroanatomically rigorous framework. In support, we documented that of adolescent depression’s core symptoms, only anhedonia, not irritability, was associated with suicidality among depressed youth. Similarly, we found that both anhedonia and entrapment were independently associated with suicidality in acutely suicidal hospitalized individuals. We also developed the reward flanker (RFT) and reward prediction error (RPET) fMRI tasks and identified brain function during reward anticipation, attainment, and positive and negative prediction errors. Notably, both RPET and a thermal pain task elicited measurable Hb activation. Additionally, utilizing an optimized segmentation and seeding approach, we mapped Hb intrinsic functional connectivity in adults and in adolescents with psychiatric symptoms. Building upon our work, we propose a tightly integrative study to test the overall hypothesis that both PVS deficiency and NVS hyperactivity underlie suicidal behavior in depressed youth. We will study 30 suicidal and 30 non-suicidal depressed adolescents, ages 12-17, group matched for age, sex, and handedness. All will have comprehensive clinical evaluations (diagnoses, behavioral measures, computerized reward task). Neuroimaging studies will include structural MRI, resting-state and task fMRI (RFT, RPET, thermal pain). Machine learning algorithms will be used to examine which PVS/NVS processes predict suicidal behavior in depressed youth.

项目概要/摘要 自杀是青少年的一个主要公共卫生问题，也是该年龄段的第二大死因， 强调调查青少年自杀的必要性。完成任务的两个最突出的风险因素 青少年自杀是过去的自杀企图和抑郁发作的诊断，两者都是独立的 意味着完成自杀的风险增加 10 至 30 倍。然而，虽然超过 80% 有自杀倾向的青少年 在尝试时出现抑郁症状，只有 30% 的抑郁青少年会尝试 自杀。这些数据表明，有过自杀企图的抑郁青少年代表了一个独特的群体。 神经生物学亚组。然而，目前我们还没有生物标志物来识别那些患有抑郁症的青少年。 会出现自杀行为。该提案解决了这一问题。我们提出的模型是： (1) 快感缺乏是 与抑郁青少年的自杀风险增加有关； (2) 正价（PVS）缺陷（奖励 预期、达到、正预测误差）和负价 (NVS) 过度活跃（负预测 错误、回避疼痛）会导致快感缺乏，并成为抑郁青少年自杀行为的基础； (3) 的 缰核 (Hb) 是一个小的边缘中枢，通过抑制 PVS/NVS 过程中的奖赏信号，在 PVS/NVS 过程中发挥关键作用。 对痛苦和失落的反应； (4) 高分辨率 MRI 的最新进展解决了先前的技术限制 研究诸如 Hb 之类的小结构。这些进展现在使我们能够研究潜在的神经元电路 PVS 和 NVS 处于严格的神经解剖学框架中。作为支持，我们记录了青少年的情况 抑郁症的核心症状，只有快感缺乏，而不是易怒，与抑郁症患者的自杀有关 青年。同样，我们发现快感缺乏和受困都与自杀独立相关 在急性自杀住院患者中。我们还开发了奖励侧卫（RFT）和奖励预测 误差 (RPET) fMRI 任务并识别奖励预期、获得以及积极和积极过程中的大脑功能 负预测错误。值得注意的是，RPET 和热痛任务均引发了可测量的 Hb 激活。 此外，利用优化的分割和播种方法，我们映射了 Hb 内在功能 成人和有精神症状的青少年的连通性。在我们工作的基础上，我们提出了一个严格的 综合研究检验 PVS 缺乏和 NVS 过度活跃导致自杀的总体假设 抑郁青少年的行为。我们将研究 30 名有自杀倾向和 30 名非自杀倾向的抑郁青少年，年龄为 12-17 岁， 年龄、性别和用手习惯相匹配的群体。所有人都将进行全面的临床评估（诊断、 行为测量，计算机化奖励任务）。神经影像学研究将包括结构 MRI、静息态 和任务功能磁共振成像（RFT、RPET、热痛）。机器学习算法将用于检查哪些 PVS/NVS 过程预测抑郁青少年的自杀行为。