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

项目总结/摘要 申请人的长期目标是发展一个研究计划，重点是了解生物学 支持外化行为的机制，包括与PTSD相关的机制，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 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资助的研究者和公认的创伤神经和内分泌机制专家 和侵略性。申请人将通过以下方式实现这一点：i）深化现有的功能磁共振成像能力， 先进的功能连接方法; ii）扩大现有的能力，在进行临床 通过获得在住院治疗机构工作的经验和获得创伤后应激障碍的培训来进行研究 评估技术;和iii）获得内分泌学研究的新能力。 PTSD影响估计超过2100万美国人，超过30%的PTSD患者对 治疗PTSD在大脑中表现为对威胁线索的神经反应增加， 情绪调节时的反应。PTSD的证据也可能存在于体内;即，作为高水平的 睾酮.睾丸激素、神经反应和PTSD之间的联系尚不清楚。更好的 了解PTSD的生物学机制可能会促进 改善干预措施。因此，该建议旨在（i）确定睾丸激素在多大程度上 反应性调节PTSD青年对威胁线索的反应;（ii）确定 睾酮反应性调节PTSD青少年的情绪调节缺陷。 申请人建议通过招募38名患有创伤后应激障碍的青少年患者和38名 比较青少年（14-17岁;一半男性;控制青春期状态）从一个大的住宅 治疗方案将采用一种平衡的重复测量设计，参与者将 完成一个功能磁共振成像范例，旨在评估对威胁的反应和情绪调节， 睾丸激素操控初步数据表明，睾酮反应可以通过非侵入性地引发， 社会挑战范例。参与者将按照这种挑战模式完成fMRI任务，或者 这是一个旨在降低T水平的范例。预计拟议的研究将显示 T的增加与对情绪刺激的反应性增加有关， 青少年PTSD患者的情绪调节由于目前对儿童创伤后应激障碍的干预策略没有考虑到 T的作用，这些数据将是重要的，在新的治疗方式的发展。 拟议的研究将在男孩镇，奥马哈，东北和爱荷华州州立大学举行。 从男孩镇住院治疗的大约500名青年中抽取，并使用 内分泌研究将在爱荷华州进行。

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.