Antecedents of Suicidal Behavior Related Neurobiology

自杀行为相关神经生物学的前因

• 批准号: 8476598
• 负责人: Joseph John Mann
• 金额: $ 201.48万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-19 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8476598
• 关键词: Address; Adolescent; Adult; Adult Children; Adverse event; Affect; Age; Aggressive behavior; Animals; Anterior; Anxiety; Apoptotic; Autopsy; Behavioral; Binding; Biological; Biological Assay; Biology; Brain; Brain imaging; Brain region; Brain-Derived Neurotrophic Factor; Candidate Disease Gene; Childhood; Clinical; Cognition; Cognitive; DNA Methylation; Data; Data Set; Development; Disease susceptibility; Emotions; Feeling suicidal; Functional Magnetic Resonance Imaging; Functional disorder; Gene Expression; Gene Expression Profile; Genes; Genetic; Glucocorticoid Receptor; Glucocorticoids; Growth; HDAC6 gene; HTR2A gene; Health; Hippocampus (Brain); Image; Individual; Knowledge; Lead; Life; Link; Literature; Major Depressive Disorder; Maternal Deprivation; Measures; Mental Depression; Methaqualone; Methods; Methylation; Modeling; Molds; Molecular; Monoamine Oxidase A; Moods; Morbidity - disease rate; Mus; Neurobiology; Neurons; Neurotransmitters; Other Genetics; Pathway interactions; Phenotype; Physiological; Positron-Emission Tomography; Prefrontal Cortex; Prevention; Probability; Psychopathology; Reporting; Risk; Role; Scanning; Serotonin; Stress; Suicide; Suicide attempt; System; Testing; Therapeutic Intervention; Time; Trier Social Stress Test; biological adaptation to stress; brain tissue; cingulate cortex; cognitive control; density; depressive symptoms; deprivation; emotion regulation; endophenotype; experience; healthy volunteer; heart rate variability; high risk; improved; indexing; interdisciplinary approach; interest; kappa opioid receptors; maternal separation; mood regulation; mortality; mouse model; novel; offspring; positive emotional state; psychologic; response; screening; stressor; suicidal behavior; suicide attempter; suicide brain; suicide rate; trait; transcriptome sequencing; young adult

DESCRIPTION (provided by applicant): Annually, the US has 30,000+ suicides and ten times as many suicide attempts. Unfortunately, mortality and morbidity have remained steady over the last two decades, suggesting that a paradigm shift in prevention is required. Such a shift hinges on improving our knowledge regarding the causes of suicidal behavior. The Conte Center will employ a multidisciplinary approach to study how reported childhood adversity can mold the diathesis for suicidal behavior. Project 1 (Arango) will use postmortem brain tissue from suicides with major depressive disorder (MDD) to examine the relationship of childhood adversity (psychological autopsy) to candidate gene expression in neurons from prefrontal cortex, anterior cingulate cortex and hippocampus, as well as growth and apoptotic factors, HPA axis indices and targets in terms of neuron and glial number and the serotonin system. Correlations with suicide and aggressive traits will be determined. Project 2 (Champagne) will use a maternal deprivation mouse model to examine effects on DNA methylation and expression of the same genes, and effects on the same brain biology and depression, anxiety and aggressive behaviors. Project 3 (Mann) and Project 4 (Ochsner) will study the same set of MDD suicide attempters, MDD nonattempters and healthy volunteers and quantify brain neurotransmitter indices and fMR responses to evaluate cognitive control of emotion, each relevant to major depression and suicidal behavior. They will evaluate the relationship of identified circuitry changes to reported childhood adversity. Project 5 (Stanley) will clinically characterize all the subjects in P3 and P4 and then determine the relationship of reported childhood adversity to aggressive traits (reactive and proactive aggression) and then relate aggression type to stress responsiveness and type of suicidal behavior. Aggression and stress responses will be measured by lab tests and by ecological momentary assessment in the real world. Findings in P5 and P3 are compared in exploratory aims (impaired serotonin function and greater aggression) and P4 (reactive individuals and weaker cognitive control over mood). Project 6 (Ogden) will use high dimensional brain imaging data to develop a novel method to measure risk for suicidal behavior. This method can then be applied to genetic and other high dimensional data sets. These projects will help elucidate how early adverse experiences affect gene expression and brain biology to increase risk of suicidal behavior later in life.

描述（由申请人提供）：每年，美国有30，000多人自杀，自杀企图是其十倍。不幸的是，死亡率和发病率在过去20年中保持稳定，这表明需要在预防方面进行模式转变。这种转变取决于我们对自杀行为原因的认识。孔蒂中心将采用多学科方法来研究报告的童年逆境如何塑造自杀行为的素质。项目1（Arango）将使用来自重度抑郁症（MDD）自杀者的死后脑组织来检查童年逆境（心理尸检）与前额叶皮层、前扣带皮层和海马神经元中候选基因表达的关系，以及生长和凋亡因子、HPA轴指数和神经元和胶质细胞数量以及5-羟色胺系统方面的目标。将确定自杀和攻击性特征的相关性。项目2（香槟）将使用母亲剥夺小鼠模型来检查对相同基因的DNA甲基化和表达的影响，以及对相同大脑生物学和抑郁、焦虑和攻击行为的影响。项目3（Mann）和项目4（Ochsner）将研究同一组MDD自杀者、MDD非自杀者和健康志愿者，并量化脑神经递质指数和fMR反应，以评估情绪的认知控制，每种情绪都与重度抑郁症和自杀行为相关。他们将评估已确定的电路变化与报告的童年逆境的关系。项目5（Stanley）将对P3和P4的所有受试者进行临床表征，然后确定报告的儿童期逆境与攻击性特征（反应性和主动性攻击）的关系，然后将攻击类型与压力反应和自杀行为类型联系起来。攻击性和压力反应将通过实验室测试和真实的世界中的生态瞬时评估来测量。P5和P3的发现在探索性目标（受损的血清素功能和更大的侵略性）和P4（反应性个体和对情绪的认知控制较弱）进行了比较。项目6（奥格登）将使用高维脑成像数据开发一种新的方法来衡量自杀行为的风险。该方法可以应用于遗传和其他高维数据集。这些项目将有助于阐明早期不良经历如何影响基因表达和大脑生物学，从而增加日后自杀行为的风险。