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.
| Flory, Janine D; Yehuda, Rachel; Grossman, Robert et al. (2009) Childhood trauma and basal cortisol in people with personality disorders. Compr Psychiatry 50:34-7 |
| Grossman, Robert; Yehuda, Rachel; New, Antonia et al. (2003) Dexamethasone suppression test findings in subjects with personality disorders: associations with posttraumatic stress disorder and major depression. Am J Psychiatry 160:1291-8 |
