CSR&D Research Career Scientist Award Application

企业社会责任

• 批准号: 10426091
• 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/10426091
• 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; 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; Psychoses; 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; schizophrenia-spectrum disorder; 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。退伍军人管理局每年为大约 100,000 名精神分裂症患者提供护理，占 占 VA 总医疗费用的近 12%。与此同时，最近的研究表明，退伍军人表现出 与美国普通人群相比，自杀风险更高。 PI 正在进行的临床认知神经科学 VA 的研究使用神经影像学和心理生理学方法，主要集中在这些方面 两个领域：阐明精神分裂症和自杀行为的神经生物学。识别有前途的新产品 精神分裂症干预和自杀预防的目标是 VA 的极其重要的目标。 PI 的 这两个领域的联邦资助和同行评审出版物的跟踪记录有助于推动该领域的发展。 PI 的新 VA CSR&D 优异奖旨在确定正常人的神经相关性和心理生理学 健康控制中的情绪反应和调节退伍军人和情绪的病理严重程度 患有重度抑郁症 (MDD) 的退伍军人的失调程度较低（非自杀性精神控制）和 自杀的高风险（自杀意念者和自杀企图者）。参与者接受基线功能 MRI 扫描和心理生理学范式提供可靠、非语言、低成本的情绪测量 处理（即情感惊吓调制）。心理生理学课程在 6 个月的随访中重复进行； 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 情绪表达失调和心理调节因素的异常，导致和 预测自杀行为并区分自杀者和自杀者对于公共卫生具有明显的重要性。 这项新资助的 VA Merit 研究有望帮助揭示生物和 心理因素会引起自杀行为，最多可能有助于前瞻性地识别退伍军人 自杀的风险。 PI 当前精神分裂症谱系研究的目标（由她之前的 VA CSR&D Merit 资助） 奖）的目的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 确定有希望的精神分裂症干预新目标，更好地了解其病理学 需要电路和潜在的遗传易感性。她的工作使用扩散张量成像 (DTI) 和 结构 MRI 来表征额颞区白质异常。 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 与白质异常和精神分裂症有关（例如 NRG1 和 ERBB4）。和她一起 西奈山 VA-伊坎医学院 (ISMMS) 的多学科同事带来了以下方面的专业知识： 在遗传学方面，PI 的工作研究了精神分裂症中白质紊乱的模型。数据是 目前正在分析并发表她最近对 60 名精神分裂症患者进行的 VA Merit 研究 人格障碍 (SPD) 和 60 名接受 MRI 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之间的关系 （分数各向异性和纤维束成像 DTI 测量）、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），以及整个认知障碍/缺陷症状 光谱。 SPD 参与者作为我们选择的表型进行研究，因为他们代表了精神分裂症的一种形式 没有长期抗精神病药物治疗、长期精神病和住院治疗的混杂因素。 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 对有前途的 VA MIRECC 研究员和临床医生科学家进行研究和指导。 PI 目前的 VA 优点是 JJPVAMC 进行的第一项研究 3T MRI 扫描。 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研究项目。

项目成果

Short communication: Diffusion tensor anisotropy in the cingulate in borderline and schizotypal personality disorder.

简短的交流：边缘型人格障碍和精神分裂型人格障碍中扣带皮层的扩散张量各向异性。

• DOI: 10.1016/j.psychres.2019.05.016
• 发表时间: 2019
• 期刊: Psychiatry research
• 影响因子: 11.3
• 作者: Goldstein,KimE;Haznedar,MMehmet;Alloy,LaurenB;Drabick,DeborahAG;McClure,MargaretM;New,AntoniaS;Chu,King-Wai;Vaccaro,Daniel;Tang,CheukY;Meyerson,David;Hazlett,ErinA
• 通讯作者: Hazlett,ErinA

Amphetamine-induced striatal dopamine release in schizotypal personality disorder.

安非他明诱导精神分裂型人格障碍纹状体多巴胺释放。

• DOI: 10.1007/s00213-020-05561-5
• 发表时间: 2020
• 期刊: Psychopharmacology
• 影响因子: 3.4
• 作者: Thompson,JudyL;Rosell,DanielR;Slifstein,Mark;Xu,Xiaoyan;Rothstein,EthanG;Modiano,YosefaA;Kegeles,LawrenceS;Koenigsberg,HaroldW;New,AntoniaS;Hazlett,ErinA;McClure,MargaretM;Perez-Rodriguez,MMercedes;Siever,LarryJ;Abi-Da
• 通讯作者: Abi-Da

Frontotemporal thalamic connectivity in schizophrenia and schizotypal personality disorder.

• DOI: 10.1016/j.pscychresns.2022.111463
• 发表时间: 2022-06
• 期刊: PSYCHIATRY RESEARCH-NEUROIMAGING
• 影响因子: 2.3
• 作者: Szeszko, Philip R.;Gohel, Suril;Vaccaro, Daniel H.;Chu, King-Wai;Tang, Cheuk Y.;Goldstein, Kim E.;New, Antonia S.;Siever, Larry J.;McClure, Margaret;Perez-Rodriguez, M. Mercedes;Haznedar, M. Mehmet;Byne, William;Hazlett, Erin A.
• 通讯作者: Hazlett, Erin A.

Anomalous Amygdala Habituation to Unpleasant Stimuli Among Unmedicated Individuals With Borderline Personality Disorder and a History of Self-Harming Behavior.

患有边缘性人格障碍和有自残行为史的未接受药物治疗的个体杏仁核对不愉快刺激的异常习惯。

• DOI: 10.1521/pedi_2020_34_495
• 发表时间: 2021
• 期刊: Journal of personality disorders
• 影响因子: 2.3
• 作者: Goldstein,KimE;Feinberg,Abigail;Corniquel,MorganB;Szeszko,JakeR;New,AntoniaS;Haznedar,MMehmet;Goodman,Marianne;Chu,King-Wai;Tang,CheukY;Hazlett,ErinA
• 通讯作者: Hazlett,ErinA

The structure of antagonism: A hierarchical model of self- and interview-rated psychopathology.

对抗的结构：自我评价和访谈评价的精神病理学的分层模型。

• DOI: 10.1037/per0000603
• 发表时间: 2023
• 期刊: Personality disorders
• 作者: Calabrese,WilliamR;MartinLopez,Maria;Koenigsberg,HaroldW;New,AntoniaS;Rosell,DanielR;Hazlett,ErinA;McClure,MargaretM;Perez-Rodriguez,MercedesM
• 通讯作者: Perez-Rodriguez,MercedesM