NEUROENDOCRINOLOGY OF CHILDHOOD ABUSE IN BPD

大约40%-80%的边缘人格障碍(BPD) 受试者儿童期经历过性虐待和/或身体虐待，但 创伤的生物后遗症在这个人群中还没有被研究过。 在此之前，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1.0 mg地塞米松抑制试验进行研究 (DST)。与重度抑郁障碍相关的HPA轴异常 (MDD)，如基线血浆皮质醇(CORT)、DST升高 不抑制，血浆淋巴细胞糖皮质激素受体减少 然而，(GR)密度在BPD受试者中并不一致。 与儿童期虐待相关的成人BPD症状学很重要 与经典创伤后应激障碍的异同 精神障碍(PTSD)。最近利用新技术进行的调查 事实证明，在定义创伤后应激障碍的神经内分泌学方面非常有用。 创伤后应激障碍患者的HPA轴功能实际上与 MDD和包括：基线血浆皮质醇升高；皮质醇升高 对专门设计的0.5 mg DST的抑制 检测到负反馈敏感度增加；以及 血浆淋巴细胞GR密度。BPD的神经生物学研究有 专注于与冲动相关的5-羟色胺能异常- 攻击性。事实上，5-羟色胺是最强大的调节剂之一。 HPA轴，从而有机会研究HPA轴- 5-羟色胺能相互作用。这笔赠款的目的是调查 与创伤后应激障碍相关的BPD的神经内分泌学，控制 儿童虐待史的变量，并收集关于 5HT1a受体反应性如何影响HPA轴损伤 互动。 我们建议将60名受试者分成四组进行研究：a)20 没有目前或终身精神障碍的受试者，B)10 目前患有创伤后应激障碍，但没有其他精神障碍的受试者 包括Axis II；C)20名患有BPD的患者，但没有其他精神疾病 除共病的Axis II外的疾病；D)10例合并BPD和PTSD。 神经内分泌评估将包括基线皮质醇、基线 淋巴细胞GR密度以及皮质醇和皮质醇抑制百分比 在0.5毫克的DST之后。试点数据表明，BPD受试者有 HPA轴异常的新模式，区别于PTSD和MDD。 特定的5HT1a激动剂伊帕西酮将用于 皮质醇反应测量面临的神经药理学挑战 评估5HT1a受体的反应性。

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.