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)生物标记物的发现和验证以及具体的挑战主题，03-MH-101：精神障碍中的生物标记物，标题为：青少年和青年自杀风险的生物标记物：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差距：确定青少年和年轻人自杀的神经回路生物标记物以及有助于其发展的生物和环境因素。每年，全世界有100多万人死于自杀，其中包括32,000多名美国人。对于青少年和年轻人来说，自杀是导致死亡的第三大原因。自杀是可以预防的。预防的关键问题是早期识别和解决其危险因素；然而，青少年和年轻人自杀的生物标志物尚未确定。青少年和青壮年自杀生物标志物的发展尤其关键，因为它不仅有助于预防这一年龄段的自杀，而且有证据表明，成年期自杀的先兆存在于儿童和青春期，在此期间，生物和环境因素改变了神经回路的发展，导致自杀易感性终生增加。这项拟议的研究汇集了一个新的多学科研究团队，专注于识别青少年和年轻人自杀的神经回路生物标记物。这包括拥有基础分子神经科学、遗传学、发育、儿童和成人精神病学、神经心理学和神经成像研究的专业知识的研究人员。有自杀未遂史的双相情感障碍(BD)青少年和年轻人将与没有自杀未遂史的BD青少年和年轻人以及没有精神障碍的青少年和年轻人进行比较。BD的自杀性将是本项目的重点，启动这一新的青少年/青年自杀研究计划，因为BD与精神障碍中自杀率最高的疾病之一有关，与青少年和年轻人的高自杀率有关。因此，对BD自杀发展的研究可能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群体的预防策略。参与这项研究的青少年和年轻人将完成对精神诊断、病程特征和症状、认知测试以及包括功能磁共振成像(FMRI)和弥散张量成像(DTI)在内的多模式磁共振成像脑扫描的全面评估。研究小组的初步发现表明，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对这种大脑回路进行深入研究。将对特定的遗传变异进行研究，并将收集有关心理社会和环境因素的全面信息，包括早期应激和药物滥用史，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记物。该方案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：全世界每年有100多万人死于自杀，其中包括32,000多名美国人，自杀是青少年和年轻人的第三大死因。自杀是可以预防的；然而，为了发现谁处于危险之中并开发有效的预防方法，需要确定青少年自杀的大脑回路生物标志物以及有助于这一回路发展的因素。这项研究将是第一批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记物，并研究其遗传和环境原因的研究之一，这种障碍与年轻人中自杀风险最高的疾病之一--双相情感障碍有关。 与公共卫生相关：全世界每年有100多万人死于自杀，其中包括32,000多名美国人，自杀是青少年和年轻人的第三大死因。自杀是可以预防的；然而，为了发现谁处于危险之中并开发有效的预防方法，需要确定青少年自杀的大脑回路生物标志物以及有助于这一回路发展的因素。这项研究将是第一批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记物，并研究其遗传和环境原因的研究之一，这种障碍与年轻人中自杀风险最高的疾病之一--双相情感障碍有关。

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.