NEUROENDOCRINOLOGY OF CHILDHOOD ABUSE IN BPD

BPD 儿童虐待的神经内分泌学

• 批准号: 2841745
• 负责人: Robert A Grossman
• 金额: $ 6.56万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2841745
• 关键词: adult human (21+); blood chemistry; borderline personality disorder; child abuse; clinical research; cortisol; dexamethasone suppression test; drug receptors; glucocorticoids; human subject; hypothalamic pituitary adrenal axis; lymphocyte; neuroendocrine system; neuropharmacology; posttraumatic stress disorder; serotonin inhibitor

Approximately 40-80 percent of borderline personality disorder (BPD) subjects have experienced childhood sexual and/or physical abuse, yet biologic sequelae of trauma has not been studied in this population. Previously, BPD was conceptualized as an affective disorder and hyphothalamic-pituitary-adrenal (HPA) axis function in BPD was investigated using the standard 1.Omg dexamethasone suppression test (DST). HPA axis abnormalaties associated with major depressive disorder (MDD) such as increased baseline plasma cortisol (CORT), DST nonsuppression, and decreased plasma lymphocyte glucocorticoid receptor (GR) density, however, were not consistently present in BPD subjects. Adult BPD symptomatology associated with childhood abuse has important similarities and differences from classical post traumatic stress disorder (PTSD). Recent investigations utilizing new techniques have proven remarkably useful in defining the neuroendocrinology of PTSD. HPA axis functioning in PTSD is virtually opposite to that observed in MDD and includes: increased baseline plasma CORT; increased CORT suppression in response to a 0.5mg DST specifically designed for detection of increased negative feedback sensitivity; and, increased plasma lymphocyte GR density. Neurobiological studies of BPD have focused on serotonergic abnormalities associated with impulsive- aggression. Indeed, serotonin is one of the most powerful modulators of the HPA axis, allowing for an opportunity to investigate HPA axis- serotonergic interactions. The purpose of this grant is to investigate the neuroendocrinology of BPD, in relation to PTSD, controlling for the variable of childhood abuse history, and collecting preliminary data on how 5HT1A receptor responsiveness may affect HPA axis-trauma interactions. We propose to study 60 subjects divided among four groups: A) 20 subjects with no current or lifetime psychiatric disorder, B) 10 subjects with current PTSD, but with no other psychiatric disorder including Axis II; C) 20 subjects with BPD, but no other psychiatric disorder except comorbid Axis II; D) 10 subjects with BPD and PTSD. Neuroendocrine assessments will include baseline CORT, baseline lymphocyte GR density, and both CORT and percent CORT suppression following a 0.5 mg DST. Pilot data suggests that BPD subjects have a novel pattern of HPA axis abnormalities, distinct from PTSD and MDD. The specific 5HT1A agonist ipsapirone will be utilized in neuropharmacological challenges with measurement of CORT response to assess 5HT1A receptor responsiveness.

大约 40-80% 的边缘性人格障碍 (BPD) 受试者在童年时期经历过性虐待和/或身体虐待，但 尚未在该人群中研究创伤的生物学后遗症。 此前，BPD 被概念化为一种情感障碍， BPD 患者下丘脑-垂体-肾上腺 (HPA) 轴功能 使用标准1.Omg地塞米松抑制试验进行研究 （夏令时）。 与重度抑郁症相关的 HPA 轴异常 (MDD)，例如基线血浆皮质醇 (CORT) 增加、DST 非抑制，血浆淋巴细胞糖皮质激素受体减少 然而，BPD 受试者的 (GR) 密度并不一致。 与儿童期虐待相关的成人 BPD 症状具有重要意义 与经典创伤后应激障碍的异同 障碍（创伤后应激障碍）。 最近利用新技术的研究已经 事实证明，它在定义 PTSD 的神经内分泌学方面非常有用。 HPA 轴在 PTSD 中的功能实际上与在 MDD 包括：基线血浆 CORT 升高； CORT增加 专门设计用于响应 0.5mg DST 的抑制 检测负反馈敏感性的增加；并且，增加了 血浆淋巴细胞 GR 密度。 BPD 的神经生物学研究 专注于与冲动相关的血清素异常 侵略。事实上，血清素是最强大的调节剂之一 HPA 轴，提供了研究 HPA 轴的机会- 血清素能相互作用。 这笔赠款的目的是调查 BPD 的神经内分泌学与 PTSD 相关，控制 儿童虐待史变量，并收集初步数据 5HT1A 受体反应性如何影响 HPA 轴创伤 互动。 我们建议研究 60 名受试者，分为四组：A) 20 当前或终生没有精神疾病的受试者，B) 10 当前患有 PTSD，但没有其他精神疾病的受试者 包括第二轴； C) 20 名受试者患有 BPD，但没有其他精神疾病 除共病轴 II 以外的疾病； D) 10 名患有 BPD 和 PTSD 的受试者。 神经内分泌评估将包括基线 CORT、基线 淋巴细胞 GR 密度以及 CORT 和 CORT 抑制百分比 0.5 mg DST 后。 试点数据表明 BPD 受试者有 HPA 轴异常的新模式，不同于 PTSD 和 MDD。 特定的 5HT1A 激动剂伊沙匹隆将用于 测量 CORT 反应的神经药理学挑战 评估 5HT1A 受体反应性。