CSR&D Research Career Scientist Award Application

企业社会责任

• 批准号: 9551820
• 负责人: ERIN A. HAZLETT
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9551820
• 关键词: Accounting; Affect; Alleles; Anisotropy; Antipsychotic Agents; Area; Award; Biological Factors; Biological Markers; Brain; Caring; Cause of Death; Chronic; Clinical; Clinical Research; Cost Measures; Data; Diffusion Magnetic Resonance Imaging; Disease; Emotional; Emotions; Exhibits; Feeling suicidal; Fiber; Funding; Genetic; Genetic Predisposition to Disease; Genotype; Goals; Health Care Costs; Health Personnel; Hospitalization; Impaired cognition; Individual; Internet; Intervention; Journals; MRI Scans; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Mediator of activation protein; Mentors; Military Personnel; Modeling; Morphologic artifacts; NRG1 gene; Neurobiology; Neurosciences Research; Paper; Participant; Pathologic; Patients; Pattern; Peer Review; Phenotype; Population; Psychiatry; Psychological Factors; Psychophysiology; Psychotic Disorders; Public Health; Publications; Publishing; Regulation; Research; Schizophrenia; Schizotypal Personality Disorder; Science; Scientist; Severities; Suicide; Suicide prevention; Susceptibility Gene; Symptoms; Time; Translating; United States; Variant; Veterans; Visit; Work; affective modulation of startle; brain circuitry; career; cognitive neuroscience; emotion dysregulation; follow-up; functional MRI scan; high risk; medical schools; multidisciplinary; neural correlate; neuroimaging; novel; pre-clinical; programs; prospective; psychologic; service member; showing emotion; suicidal; suicidal behavior; suicidal risk; suicide attempter; tractography; white matter

Schizophrenia spectrum disorders and suicidal behavior are major public health problems affecting Veterans. Each year, the VA provides care to approximately 100,000 schizophrenia patients, accounting for nearly 12% of the VA’s total healthcare costs. At the same time, recent studies indicate that Veterans exhibit higher suicide risk compared with the general U.S. population. The PI’s ongoing clinical cognitive neuroscience research at the VA uses neuroimaging and psychophysiological approaches and primarily focuses on these two areas: elucidating the neurobiology of schizophrenia and suicidal behavior. Identification of promising new targets for intervention in schizophrenia and suicide prevention are critically important goals of the VA. The PI’s track record of federal funding and peer-reviewed publications in these two areas has helped advance the field. The PI’s new VA CSR&D Merit Award aims to identify the neural correlates and psychophysiology of normal emotional reactivity and regulation in healthy control Veterans and pathological severity of emotion dysregulation in Veterans with major depressive disorder (MDD) at low (non-suicidal psychiatric controls) and high-risk (suicidal ideators and suicide attempters) for suicide. Participants receive baseline functional MRI scans and a psychophysiological paradigm that provides a reliable, non-verbal, low-cost measure of emotion processing (i.e. affective startle modulation). The psychophysiology session is repeated at a 6-month follow-up; clinical symptom assessments are done at baseline, 6-, and 12-month follow-up. Understanding brain circuitry anomalies underlying dysregulated emotional expression and psychological mediators that give rise to and predict suicidal behavior and distinguish between ideators and attempters has clear public health importance. This newly-funded VA Merit study promises to help uncover the mechanisms by which biological and psychological factors give rise to suicidal behavior and may aid in prospectively identifying Veterans at greatest risk for suicide. The goal of the PI’s current schizophrenia-spectrum research (funded by her previous VA CSR&D Merit Award) is to begin to translate pre-clinical scientific research in schizophrenia into the clinical arena. In order to identify promising new targets for intervention in schizophrenia, a better understanding of its pathological circuitry and underlying genetic susceptibilities is required. Her work uses diffusion tensor imaging (DTI) and structural MRI to characterize white matter abnormalities in frontal-temporal regions. DTI fiber tractography allows quantification of the integrity of white matter connectivity in the brain. Various susceptibility genes are implicated in white matter abnormalities and schizophrenia (e.g., NRG1 and ERBB4). Together with her multidisciplinary VA-Icahn School of Medicine at Mount Sinai (ISMMS) colleagues who bring expertise in genetics, the PI’s work investigates a model of white matter disorganization in schizophrenia. Data are currently being analyzed and published from her recent VA Merit study of 60 individuals with schizotypal personality disorder (SPD) and 60 healthy controls who received MRI and were genotyped. This work evaluates white matter organization and examines the relationship between white matter connectivity (fractional anisotropy and tractography DTI measures), white matter volume (structural MRI), allelic variation in two underlying susceptibility genes (NRG1 and ERBB4), and cognitive impairment/deficit symptoms across the spectrum. SPD participants are studied as our choice of phenotype as they represent a form of schizophrenia without the confounding artifacts of chronic antipsychotic treatment, long-term psychosis, and hospitalization. Impact: This Research Career Scientist Award will allow the PI to augment her highly collaborative VA research and mentoring of promising VA MIRECC fellows and clinician-scientists. The PI’s current VA Merit is the first study at the JJPVAMC to conduct research 3T MRI scans. The PI’s goal is to further expand her MRI research program in schizophrenia and suicidal behavior at the JJPVAMC.

精神分裂症谱系障碍和自杀行为是影响 退伍军人。每年，退伍军人管理局为大约10万名精神分裂症患者提供护理，占 几乎占退伍军人管理局总医疗费用的12%。与此同时，最近的研究表明，退伍军人表现出 与普通美国人相比，自杀风险更高。PI正在进行的临床认知神经科学 退伍军人管理局的研究使用神经成像和心理生理学方法，主要集中在以下几个方面 两个领域：阐明精神分裂症和自杀行为的神经生物学。有前途的新产品的识别 精神分裂症的干预目标和自杀预防是退伍军人管理局至关重要的目标。少年派的 这两个领域的联邦资助和同行评议出版物的记录帮助推动了这一领域的发展。 PI的新的VA CSR&D优秀奖旨在确定正常人的神经相关性和心理生理学 健康对照退伍军人情绪反应性与情绪病理严重度的关系 患有严重抑郁障碍(MDD)的退伍军人在低血压(非自杀精神对照)和 自杀高危人群(自杀意念者和自杀未遂者)。参与者接受基线功能磁共振成像 扫描和提供可靠的、非语言的、低成本的情绪测量的心理生理学范式 加工(即情感惊吓调制)。在6个月的随访中重复心理生理学课程； 临床症状评估在基线、6个月和12个月的随访中进行。了解大脑回路 潜在的情绪表达失调和心理调节异常导致和 预测自杀行为并区分理想者和未遂者具有明显的公共卫生重要性。 这项新资助的VA Merit研究承诺帮助揭示生物和 心理因素会导致自杀行为，并可能在最大程度上有助于前瞻性地识别退伍军人 有自杀的风险。 私家侦探目前精神分裂症谱研究的目标(由她之前的VA CSR&D功绩资助 奖)是开始将精神分裂症的临床前科学研究转化为临床领域。为了 为精神分裂症的干预找到有希望的新靶点，更好地了解其病理 电路和潜在的遗传易感性是必需的。她的工作使用了扩散张量成像(DTI)和 额颞区脑白质异常的结构磁共振特征。DTI纤维束成像 可以量化大脑中白质连接的完整性。各种易感基因有 与脑白质异常和精神分裂症有关(如NRG1和ERBB4)。和她一起 多学科弗吉尼亚-伊坎西奈山医学院(ISMMS)的同事们带来了专业知识 遗传学方面，PI的工作调查了精神分裂症中脑白质紊乱的模型。数据是 目前正在分析并发表在她最近对60名分裂类型患者进行的VA Merit研究中 人格障碍(SPD)患者和60例接受MRI检查并进行基因分型的健康对照。这部作品 评估白质组织并检查白质连接性之间的关系 (分数各向异性和纤维束成像DTI测量)，脑白质体积(结构MRI)，等位基因变异 两个潜在的易感基因(NRG1和ERBB4)和认知障碍/缺陷症状 频谱。SPD参与者被作为我们选择的表型进行研究，因为他们代表了一种精神分裂症 没有慢性抗精神病药物治疗、长期精神病和住院治疗的令人困惑的人工制品。 影响：这个研究职业科学家奖将允许PI增强她高度合作的退伍军人管理局 对有前途的退伍军人事务部研究员和临床科学家进行研究和指导。少年警卫队目前的退伍军人荣誉奖 在JJPVAMC进行的第一项研究是3T磁共振扫描。私家侦探的目标是进一步扩大她的核磁共振 JJPVAMC的精神分裂症和自杀行为研究项目。