Biomarkers of Suicide Risk in Adolescents and Young Adults: Factors that Con

描述（由申请人提供）：本申请涉及广泛的挑战领域（03）生物标志物发现和验证以及特定的挑战主题，03-MH-101：精神疾病中的生物标志物，标题为：青少年和年轻人自杀风险的生物标志物：导致双相情感障碍高风险的因素。这项拟议的研究解决了可能对自杀预防进展产生重大影响的知识方面的一个关键空白：确定青少年和年轻人自杀倾向的神经回路生物标志物以及有助于其发展的生物和环境因素。每年，全世界有超过100万人死于自杀，其中包括32，000多名美国人。对于青少年和年轻人来说，自杀是第三大死亡原因。自杀是可以预防的。其预防的关键问题是早期识别和解决其风险因素;然而，尚未确定青少年和年轻人自杀的生物标志物。青少年和年轻人自杀生物标志物的发展尤其重要，因为它不仅有助于预防这一年龄组的自杀，而且有证据表明，在儿童和青少年时期存在自杀的前因，在此期间，生物和环境因素改变了神经回路的发展，导致自杀脆弱性终身增加。这项拟议的研究汇集了一个新的多学科研究小组，专注于识别青少年和年轻人自杀倾向的神经回路生物标志物。这包括具有基础分子神经科学，遗传，发育，儿童和成人精神病学，神经心理学和神经影像学研究专业知识的研究人员。将有自杀企图史的双相情感障碍（BD）青少年和年轻人与无自杀企图史的BD青少年和年轻人以及无精神疾病的青少年和年轻人进行比较。BD的自杀将是该项目的重点，启动青少年/年轻人自杀研究的新项目，因为BD与精神疾病中自杀率最高的疾病之一相关，并且与青少年和年轻人的高自杀率相关。因此，对BD自杀发展的研究可能会导致与自杀高风险相关的生物标志物的发展，并有助于制定针对这一高危人群的预防策略。参与本研究的青少年和年轻人将完成对精神病诊断、病程特征和症状、认知测试和多模态磁共振成像脑部扫描（包括功能性磁共振成像（fMRI）和弥散张量成像（DTI））的综合评估。研究小组的初步发现涉及情绪和冲动调节的大脑回路。将使用最先进的大脑扫描图像分析方法深入研究这种大脑回路。将对特定的遗传变异进行研究，并收集有关心理社会和环境因素的综合信息，包括早期压力和药物滥用史，以研究可能影响自杀风险的遗传和环境因素。该项目将启动这项研究计划，重点是确定青少年和年轻人自杀的原因和生物标志物。该计划的长期目标包括开发早期发现自杀风险的新方法和有效的预防方法。相关性：每年，全世界有超过100万人死于自杀，其中包括32，000多名美国人，自杀是青少年和年轻人死亡的第三大原因。它是可以预防的;然而，为了发现谁有自杀的危险，并制定有效的预防方法，需要确定青年自杀倾向的脑回路生物标志物，以及促进这种回路发展的因素。这项研究将是第一个调查，利用全面和深入的方法来阐明青少年和年轻人自杀的脑回路生物标志物，并研究他们的遗传和环境原因，与青少年自杀风险最高的疾病之一，双相情感障碍。 公共卫生相关性：每年，全世界有超过100万人死于自杀，其中包括32，000多名美国人，自杀是青少年和年轻人死亡的第三大原因。它是可以预防的;然而，为了发现谁有自杀的危险，并制定有效的预防方法，需要确定青年自杀倾向的脑回路生物标志物，以及促进这种回路发展的因素。这项研究将是第一个调查，利用全面和深入的方法来阐明青少年和年轻人自杀的脑回路生物标志物，并研究他们的遗传和环境原因，与青少年自杀风险最高的疾病之一，双相情感障碍。

DESCRIPTION (provided by applicant): This application addresses the broad Challenge Area (03) Biomarker Discovery and Validation and specific Challenge topic, 03-MH-101: Biomarkers in Mental Disorders and is entitled: Biomarkers of Suicide Risk in Adolescents and Young Adults: Factors that Contribute to High Risk in Bipolar Disorder. The proposed study addresses a critical gap in knowledge that could have a major impact on progress in suicide prevention: identification of neural circuitry biomarkers of adolescent and young adult suicidality and the biological and environmental factors that contribute to their development. Each year, over one million individuals lose their lives to suicide worldwide, including more than 32,000 Americans. For adolescents and young adults, suicide is the 3rd leading cause of mortality. Suicide is preventable. The critical issues in its prevention are its early identification and addressing its risk factors; however, biomarkers for adolescent and young adult suicidality have not been identified. The development of biomarkers of suicide in adolescents and young adults is especially critical, as it could contribute not only to prevention of suicide in this age group, but evidence suggests that antecedents to suicide through adulthood are present in childhood and adolescence during which biological and environmental factors alter the development of neural circuitry leading to lifelong increases in suicide vulnerability. The proposed study brings together a new multidisciplinary team of investigators to focus on the identification of neural circuitry biomarkers of adolescent and young adult suicidality. This includes investigators with expertise that spans basic molecular neuroscience, genetic, development, child and adult psychiatry, neuropsychology and neuroimaging study. Adolescents and young adults with bipolar disorder (BD) with a history of suicide attempts will be compared to adolescents and young adults with BD without a history of suicide attempts, as well as adolescents and young adults who do not have a psychiatric disorder. Suicidality in BD will be the focus of this project, initiating this new program of research in adolescent/young adult suicide, as BD is associated with one of the highest rates of suicide from amongst psychiatric disorders and is associated with a high rate of suicide in adolescents and young adults. Thus, study of development of suicide in BD could lead to the development of biomarkers associated with high risk for suicide and aid the development of prevention strategies that could be targeted to this high-risk group. The adolescents and young adults participating in this study will complete comprehensive assessments of psychiatric diagnosis, illness course features and symptoms, cognitive testing, and multi-modality magnetic resonance imaging brain scanning including functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). Preliminary findings of the research team implicate the brain circuitry of emotion and impulse regulation. This brain circuitry will be investigated intensively using state-of-the-art brain scanning image analysis methods. Study of specific genetic variations will be performed and comprehensive information regarding psychosocial and environmental factors, including history of early stress and substance abuse, will be collected in order to study genetic and environmental factors that might influence risk for suicide. This project will initiate this program of research focused on identifying the causes and biomarkers for adolescent and young adult suicide. Long-term goals for this program include the development of new methods for early detection of risk for suicide and effective prevention methods. Relevance: Each year, over one million individuals lose their lives to suicide worldwide, including more than 32,000 Americans, and suicide is the 3rd leading cause of death in adolescents and young adults. It is preventable; however, in order to detect who is at risk and to develop effective prevention methods, identification of the brain circuitry biomarkers of suicidality in youth and the factors that contribute to the development of this circuitry are needed. This study would be one of the first investigations to utilize a comprehensive and intensive approach to elucidate brain circuitry biomarkers for suicide among adolescents and young adults and to study their genetic and environmental causes in a disorder associated with one of the highest risks for suicide among youths, bipolar disorder. PUBLIC HEALTH RELEVANCE: Each year, over one million individuals lose their lives to suicide worldwide, including more than 32,000 Americans, and suicide is the 3rd leading cause of death in adolescents and young adults. It is preventable; however, in order to detect who is at risk and to develop effective prevention methods, identification of the brain circuitry biomarkers of suicidality in youth and the factors that contribute to the development of this circuitry are needed. This study would be one of the first investigations to utilize a comprehensive and intensive approach to elucidate brain circuitry biomarkers for suicide among adolescents and young adults and to study their genetic and environmental causes in a disorder associated with one of the highest risks for suicide among youths, bipolar disorder.