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; 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的主要公共卫生问题 退伍军人。每年，VA为大约100,000名精神分裂症患者提供护理 弗吉尼亚州总医疗保健总成本的近12％。同时，最近的研究表明退伍军人表现出 与美国普通人口相比，自杀风险更高。 PI正在进行的临床认知神经科学 VA的研究采用神经影像学和心理生理学方法，主要关注这些方法 两个领域：阐明精神分裂症和自杀行为的神经生物学。诺言新的识别 干预精神分裂症和预防自杀的目标是VA的至关重要的目标。 PI的 在这两个领域的联邦资金和同行评审出版物的记录有助于进步。 PI的新VA CSR＆D优异奖旨在确定正常的神经相关性和心理生理学 健康控制退伍军人的情绪反应性和调节性和情绪的病理严重程度 低抑郁症（MDD）的退伍军人失调（非杀伤性精神病对照）和 自杀的高风险（自杀构想者和自杀式意见）。参与者获得基线功能性MRI 扫描和心理生理范式，可提供可靠的，非语言，低成本的情感测量 处理（即情感惊吓调制）。心理生理学会议在6个月的随访中重复； 临床症状评估是在基线，6个月和12个月的随访中进行的。了解脑电路 引起和 预测自杀行为并区分思想和思想，明显的公共健康重要性。 这项新资助的VA功绩研究有望帮助揭示生物学和生物学的机制 心理因素会引起自杀行为，并可能有助于前瞻性地确定退伍军人 自杀的风险。 PI目前的精神分裂症 - 光谱研究的目标（由她以前的VA CSR和D的优点资助 奖项）将开始将精神分裂症前临床前科学研究转化为临床领域。为了 确定对精神分裂症干预的新目标，对其病理的更好理解 需要电路和潜在的遗传敏感性。她的工作使用扩散张量成像（DTI）和 结构性MRI表征前颞区域中的白质异常。 DTI纤维拖拉机 允许大脑中白质连通性的完整性数量。各种敏感性基因是 以白质异常和精神分裂症实施（例如NRG1和ERBB4）。和她一起 西奈山（ISMMS）同事的多学科VA-ICAHN医学院，他们带来了专业知识 遗传学，PI的工作研究了精神分裂症中白质混乱的模型。数据是 目前正在从她最近对60名Schizotypal的人的VA优点研究中进行分析和发表 人格障碍（SPD）和60种接受MRI并进行基因分型的健康对照。这项工作 评估白质组织并检查白质连接性之间的关系 （分数各向异性和拖拉术DTI测量值），白质体积（结构MRI），等位基因变化 两个潜在的敏感性基因（NRG1和ERBB4），以及跨整个的认知障碍/赤字符号 光谱。 SPD参与者被研究为我们对表型的选择，因为它们代表了一种精神分裂症的形式 没有慢性抗精神病药物，长期精神病和住院治疗的混淆。 影响：这项研究职业科学家奖将使PI能够增强她高度协作的VA 承诺的VA Mirecc研究员和临床科学家的研究和心理。 Pi当前的VA功绩是 在JJPVAMC进行研究3T MRI扫描的第一项研究。 PI的目标是进一步扩展她的MRI JJPVAMC的精神分裂症和自杀行为的研究计划。