Childhood Trauma in the Adrenergic and HPA-Axis Regulation and Symptoms of PMDD

肾上腺素和 HPA 轴调节中的儿童创伤以及经前抑郁症 (PMDD) 的症状

• 批准号: 7261025
• 负责人: SUSAN S. GIRDLER
• 金额: $ 45.64万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7261025
• 关键词: Absence of pain sensation; Adrenal Glands; Adrenergic Agents; Adrenergic Antagonists; Adrenergic Receptor; Adult; Age; Age-Years; Analgesics; Animals; Area; Battered Women; Biological; Biological Markers; Blood Pressure; Cardiac Output; Cardiovascular system; Child Abuse; Child Sexual Abuse; Childhood; Clinical; Condition; Control Groups; Corticotropin; Coupled; Daily; Data; Data Analyses; Development; Diagnosis; Disease regression; Dose; Double-Blind Method; Emotional; Endorphins; Event; Exhibits; Family history of; Female; Genetic Crossing Over; Heart Rate; Heating; Hydrocortisone; Hyperalgesia; Hypothalamic structure; Impedance Cardiography; Interview; Isoproterenol; Life; Link; Longitudinal Studies; Luteal Phase; Measures; Mediating; Mental Depression; Mental disorders; Moods; Nervous System Physiology; Norepinephrine; Output; Pain; Pain Threshold; Pathway interactions; Patients; Pattern; Perception; Phase; Physiological; Pilot Projects; Pituitary Gland; Placebo Control; Placebos; Plasma; Play; Post-Traumatic Stress Disorders; Principal Investigator; Procedures; Propranolol; Psyche structure; Questionnaires; Randomized; Rate; Receptor Activation; Recording of previous events; Recruitment Activity; Regulation; Relative (related person); Reporting; Research; Research Personnel; Rest; Risk; Role; Severities; Stress; Subgroup; Sympathetic Nervous System; Symptoms; Syndrome; Techniques; Testing; Tourniquets; Woman; Women' s Group; Work; adrenergic; base; behavior measurement; chronic pain; comparison group; day; disorder control; dysphoria; hypothalamic-pituitary-adrenal axis; indexing; insight; pain inhibition; pediatric trauma; physical abuse; premenstrual dysphoric disorder; programs; prospective; receptor function; response; stress related disorder; stressor; trait

DESCRIPTION (provided by applicant): Prior research indicates that women with premenstrual dysphoric disorder (PMDD) have alterations in sympathetic nervous system (SNS) and adrenergic receptor (AR) function. Our work suggests that PMDD women with histories of sexual and physical abuse, especially childhood abuse (CA) show even greater adrenergic dysregulation, since they exhibit greater heart rate and blood pressure levels, greater B-AR responsivity and lower plasma norepinephrine (NE) relative to non-abused PMDD women. Animal studies clearly indicate a role for B-AR activation in producing hyperalgesia, while NE pathways and HPA-axis activation are involved in pain inhibition. Thus, alterations in B-AR function and diminished NE and cortisol output in PMDD women with abuse may have implications for the hyperalgesia that has been documented in PMDD. It is hypothesized that increased B-AR responsivity coupled with blunted NE will contribute to worse premenstrual symptoms and to hyperalgesia to experimental pain in PMDD women with prior CA. Sixty PMDD and 90 non-PMDD women will be tested in the luteal phase of the menstrual cycle for SNS (e.g., plasma NE, blood pressure) and HPA-axis (cortisol, ACTH, B-end) activation at rest and during stress, B-AR responsivity, and pain sensitivity to ischemic, thermal heat, and cold pain. Five groups will be compared for differences in pain sensitivity and relationship to physiological measures: 1) PMDD women with prior CA (n=30); 2) never abused PMDD women (n=30); 3) non-PMDD women with prior CA (n=30); 4) never abused non-PMDD women (n=30); and 5) non-PMDD women with no abuse and no psychiatric histories (n=30) as a healthy control group. Since our prelim studies show that all women with abuse have lower cortisol and non- PMDD women with CA show some degree of adrenergic dysregulation, we predict a rank order of effects PMDD/CA+>non-PMDD/CA+>PMDD/CA->non-PMDD/CA- for adrenergic dysregulation and hyperalgesia. Following this testing, using double-blind, placebo-controlled, cross-over procedures, all women will be retested in 2 subsequent luteal phases for SNS measures, pain sensitivity, and dysphoric mood; once during a low dose, i.v. propranolol session (0.1 mg/kg) and once during placebo. Since propranolol is a B-AR blocker, we intend to use propranolol as a pharmacological probe to investigate SNS and adrenergic factors that contribute to hyperalgesia and dysphoric mood in PMDD. We hypothesize that propranolol will be associated with differentially greater normalization of SNS, NE and hyperalgesia measures, and greater reductions in dysphoria in PMDD women with CA. These results are intended to provide important insights into the pathophysiological significance of altered adrenergic activation in the subgroup of PMDD women with CA.

描述（由申请人提供）：先前的研究表明，经前烦躁不安障碍（PMDD）的女性具有交感神经系统（SNS）和肾上腺素能受体（AR）功能的改变。我们的工作表明，具有性和身体虐待病史的PMDD妇女，尤其是儿童虐待（CA）表现出更大的肾上腺素能失调，因为相对于未虐待的PMDD妇女，她们表现出更高的心率和血压水平，更高的B-AR反应性和较低的血浆去甲肾上腺素（NE）。动物研究清楚地表明，B-AR激活在产生痛觉过敏中的作用，而NE途径和HPA轴激活参与疼痛抑制。因此，BAR功能的改变以及滥用PMDD女性的NE和皮质醇输出减少可能对PMDD中已记录的Hypergergusia有影响。假设BAR的反应性升高，结合NE的NE将导致更严重的经前症状，并导致过度过敏，导致先前CA的PMDD女性的实验性疼痛。 60名PMDD和90名非PMDD女性将在月经周期的黄体阶段进行SNS（例如，血浆NE，血压）和HPA轴（皮质醇，ACTH，ACTH，B端）激活的静止和压力，B-AR响应率，B-AR响应率以及对缺血性疼痛的疼痛敏感性。将比较五组疼痛敏感性和与生理措施的关系的差异：1）PMDD患有先验CA的PMDD女性（n = 30）； 2）切勿虐待PMDD妇女（n = 30）； 3）具有先验CA的非PMDD女性（n = 30）； 4）切勿滥用非PMDD妇女（n = 30）； 5）没有虐待且没有精神病学病史的非PMDD女性作为健康对照组。由于我们的初步研究表明，所有患有滥用的女性皮质醇和非PMDD妇女患有CA的妇女表现出一定程度的肾上腺功能失调，因此我们预测，pMDD/CA+> non-pmdd/ca+> pmdd/ca-+> pmdd/ca-> pmdd/ca-> non-pmdd/ca-> non-pmdd/ca-> non-pmdd/ca-的肾上腺素失调和超级疾病的效果。在此测试之后，使用双盲，安慰剂控制的交叉程序，所有妇女将在随后的2个黄体阶段重新测试，以进行SNS测量，疼痛敏感性和烦躁不安的情绪。一次在低剂量期间，i.v.普萘洛尔疗法（0.1 mg/kg），一次安慰剂。由于普萘洛尔是B-AR阻滞剂，因此我们打算使用普萘洛尔作为药理学探测器，以研究有助于PMDD中有助于痛苦和烦躁不安的SNS和肾上腺素能因子。我们假设普萘洛尔将与SNS，NE和Hypergerseia测度的差异更大的归一化以及PMDD女性CA的烦躁不安的降低相关。这些结果旨在提供有关CA的PMDD妇女亚组改变肾上力激活的病理生理意义的重要见解。