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， 强调有必要调查青少年自杀的两个最突出的危险因素。 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 然而，超过 80% 有自杀倾向的青少年的自杀风险增加了 10 至 30 倍。 在尝试时出现抑郁症状，只有 30% 的抑郁青少年会尝试 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。 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。 我们提出的模型是：（1）快感缺失。 (2) 正价（PVS）缺陷（奖励 预期、达到、正预测误差）和负价（NVS）多动（负预测 错误、回避疼痛）会导致抑郁青少年的快感缺失和自杀行为；(3) 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。 对疼痛和损失的反应；(4) 高分辨率 MRI 的最新进展解决了先前的技术限制 研究血红蛋白等小结构现在使我们能够研究潜在的神经回路。 PVS 和 NVS 在神经解剖学严格的框架中作为支持，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 同样，我们发现快感缺失和受困都与自杀独立相关。 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 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 在我们的工作的基础上，我们提出了一个紧密联系的成人和有精神症状的青少年。 综合研究检验 PVS 缺乏和 NVS 过度活跃是自杀倾向的总体假设 我们将研究 30 名有自杀倾向和 30 名未自杀的抑郁青少年，年龄为 12-17 岁。 年龄、性别和利手习惯相匹配的小组所有人都将进行全面的临床评估（诊断、 行为测量、计算机奖励任务）。神经影像研究将包括结构 MRI、静息态。 和任务 fMRI（RFT、RPET、热疼痛）将用于检查哪些 PVS/NVS。 过程预测抑郁青少年的自杀行为。