THE ROLE OF TESTOSTERONE IN MODULATING NEURAL RESPONSE TO THREAT CUES AND DURING EMOTION REGULATION IN POSTTRAUMATIC STRESS DISORDER

睾酮在调节对威胁线索的神经反应和创伤后应激障碍情绪调节中的作用

• 批准号: 9899114
• 负责人: Stuart F. White
• 金额: $ 11.09万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899114
• 关键词: Address; Adolescent; Adult; Affect; Aggressive behavior; American; Amygdaloid structure; Applications Grants; Attention; Behavior; Biological; Biological Markers; Brain; Childhood; Clinical Research; Competence; Cues; Data; Development; Disease; Economics; Endocrine; Endocrine system; Endocrinology; Failure; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Gender; Goals; Hormonal; Hormones; Human; Hydrocortisone; Individual; Intervention; Iowa; Link; Measures; Mental disorders; Methodology; Methods; Mission; Modality; National Institute of Mental Health; Neurophysiology - biologic function; Neurosecretory Systems; Participant; Patients; Positioning Attribute; Post-Traumatic Stress Disorders; Process; Psychopathology; Reporting; Research; Research Personnel; Residential Treatment; Role; Salivary; Scanning; Sex Differences; Site; Stimulus; Symptoms; System; Techniques; Testing; Testosterone; Time; Training; Trauma; United States National Institutes of Health; Woman; Work; Youth; adolescent patient; aged; attentional control; base; behavior influence; biomarker identification; boys; cost; design; emotion regulation; emotional stimulus; experience; externalizing behavior; gender difference; improved; male; novel; programs; recruit; relating to nervous system; response; social; trauma exposure; treatment program; treatment strategy

PROJECT SUMMARY/ABSTRACT The applicant's long-term objective is to develop a research program focusing on understanding biological mechanisms underpinning externalizing behaviors, including those associated with PTSD, in order to facilitate the development of improved strategies to reduce these behaviors. This is consistent with the NIMH's mission to reduce the burden of mental illness. The applicant's medium-term objective is to become an independent, NIH-funded investigator and a recognized expert in neural and endocrine mechanisms implicated in trauma and aggression. The applicant will accomplish this by i) deepening an existing competency in fMRI with advanced functional connectivity methods; ii) broadening an existing competency in conducting clinical research by gaining experience working in a residential treatment facility and by acquiring training in PTSD assessment techniques; and iii) gaining new competency in endocrinology research. PTSD effects an estimated > 21 million Americans and >30% of PTSD patients do not respond to treatment. PTSD may manifest in the brain as increased neural response to threat cues and disrupted neural responses during emotion regulation. Evidence of PTSD may also present in the body; i.e., as high levels of testosterone. The link between testosterone, neural responses and PTSD is poorly understood. A better understanding of the biological mechanisms underpinning PTSD would likely facilitate the development of improved interventions. Thus, this proposal aims to (i) determine the extent to which testosterone responsiveness modulates response to threat cues in youth with PTSD and (ii) determine the extent to which testosterone responsiveness modulates emotion regulation deficits in youth with PTSD. The applicant proposes to accomplish these aims by recruiting 38 adolescent patients with PTSD and 38 comparison adolescents (aged 14-17; half male; controlling for pubertal status) from a large residential treatment program. A counter-balanced repeated-measures design will be employed where participants will complete an fMRI paradigm designed to assess response to threat and emotion regulation following a testosterone manipulation. Pilot data indicates that a testosterone response can be non-invasively elicited by a social challenge paradigm. Participants will complete the fMRI task following this challenge paradigm or following a paradigm designed to reduce T levels. It is anticipated that the proposed study will show the extent to which an increase in T is associated with an increased responsiveness to emotional stimuli and reduced emotion regulation in youth with PTSD. As current intervention strategies for pediatric PTSD do not consider the role of T, these data will be important in the development of novel treatment modalities. The proposed research would take place at Boys Town, Omaha, NE and Iowa State Univ. Participants will be drawn from the approximately 500 youth in residential treatment at Boys Town and scanned using the on- site dedicated research scanner, while the endocrine research would take place at Iowa State.

项目概要/摘要 申请人的长期目标是开发一个专注于了解生物学的研究计划 支持外化行为的机制，包括与 PTSD 相关的行为，以促进 制定改进的策略来减少这些行为。这与 NIMH 的使命是一致的 以减轻精神疾病的负担。申请人的中期目标是成为一个独立的、 美国国立卫生研究院 (NIH) 资助的研究人员和创伤相关神经和内分泌机制领域公认的专家 和侵略性。申请人将通过以下方式实现这一目标：i) 深化 fMRI 的现有能力 先进的功能连接方法； ii）扩大现有的临床能力 通过获得在住院治疗机构工作的经验以及接受创伤后应激障碍（PTSD）培训来进行研究 评估技术； iii) 获得内分泌学研究的新能力。 据估计，PTSD 影响了超过 2100 万美国人，并且超过 30% 的 PTSD 患者对治疗没有反应 治疗。创伤后应激障碍（PTSD）可能在大脑中表现为对威胁线索的神经反应增加和神经元紊乱 情绪调节过程中的反应。 PTSD 的证据也可能存在于体内；即，随着高水平 睾酮。人们对睾酮、神经反应和创伤后应激障碍之间的联系知之甚少。更好的 了解创伤后应激障碍 (PTSD) 的生物学机制可能会促进 改进干预措施。因此，该提案的目的是 (i) 确定睾丸激素发挥作用的程度 反应能力调节患有创伤后应激障碍 (PTSD) 的青少年对威胁线索的反应，并且 (ii) 确定 睾酮反应可调节患有创伤后应激障碍 (PTSD) 的青少年的情绪调节缺陷。 申请人建议通过招募 38 名患有 PTSD 的青少年患者和 38 名患有 PTSD 的青少年患者来实现这些目标。 比较来自大型住宅区的青少年（14-17 岁；一半男性；控制青春期状态） 治疗方案。将采用平衡重复测量设计，参与者将 完成功能磁共振成像范式，旨在评估对威胁和情绪调节的反应 睾酮操纵。试验数据表明，睾酮反应可以通过非侵入性的方式引发 社会挑战范式。参与者将按照此挑战范式完成功能磁共振成像任务或 遵循旨在降低 T 水平的范例。预计拟议的研究将表明 T 的增加与对情绪刺激的反应性增加和减少有关 患有创伤后应激障碍 (PTSD) 的青少年的情绪调节。由于目前针对儿科 PTSD 的干预策略没有考虑 T 的作用，这些数据对于开发新的治疗方式非常重要。 拟议的研究将在内布拉斯加州奥马哈男孩镇和爱荷华州立大学进行。参与者将 从男孩镇住院治疗的约 500 名青少年中抽取，并使用在线扫描仪进行扫描 现场专用研究扫描仪，而内分泌研究将在爱荷华州进行。

项目成果

Adolescents show differential dysfunctions related to Alcohol and Cannabis Use Disorder severity in emotion and executive attention neuro-circuitries.

• DOI: 10.1016/j.nicl.2018.06.005
• 发表时间: 2018
• 期刊: NeuroImage. Clinical
• 作者: Aloi J;Blair KS;Crum KI;Meffert H;White SF;Tyler PM;Thornton LC;Mobley AM;Killanin AD;Adams KO;Filbey F;Pope K;Blair RJR
• 通讯作者: Blair RJR

Neural correlates of conventional and harm/welfare-based moral decision-making.

• DOI: 10.3758/s13415-017-0536-6
• 发表时间: 2017-12
• 期刊: Cognitive, affective & behavioral neuroscience
• 作者: White SF;Zhao H;Leong KK;Smetana JG;Nucci LP;Blair RJR
• 通讯作者: Blair RJR

Increases in Stressors Prior to-Versus During the COVID-19 Pandemic in the United States Are Associated With Depression Among Middle-Aged Mothers.

• DOI: 10.3389/fpsyg.2021.706120
• 发表时间: 2021
• 期刊: Frontiers in psychology
• 影响因子: 3.8
• 作者: Taylor BK;Frenzel MR;Johnson HJ;Willett MP;White SF;Badura-Brack AS;Wilson TW
• 通讯作者: Wilson TW

Moderation of prior exposure to trauma on the inverse relationship between callous-unemotional traits and amygdala responses to fearful expressions: an exploratory study.

• DOI: 10.1017/s0033291718000156
• 发表时间: 2018-11
• 期刊: Psychological medicine
• 影响因子: 6.9
• 作者: Meffert H;Thornton LC;Tyler PM;Botkin ML;Erway AK;Kolli V;Pope K;White SF;Blair RJR
• 通讯作者: Blair RJR

Changing role of the amygdala in affective and cognitive traits between early and late adulthood.

• DOI: 10.3389/fpsyt.2023.1033543
• 发表时间: 2023
• 期刊: FRONTIERS IN PSYCHIATRY
• 影响因子: 4.7
• 作者: Doucet, Gaelle E.;Kruse, Jordanna A.;Hamlin, Noah;Oleson, Jacob J.;White, Stuart F.
• 通讯作者: White, Stuart F.