The specifc aim of the proposed project is to test the hypothesis that history of childhood trauma as measured by the Childhood Trauma Questionnaire (CTQ) is associated with elevated CSF corticotropinreleasing factor (CRF) as measured by basal assessment of CSF CRF levels, and associated with elevated ACTH responses to oCRF Challenge in adult personality disorder (i.e. borderline personality disorder) subjects. This study will compare CSF CRF and ACTH response to oCRF in 10 personality disorder subjects with high scores on the Childhood Trauma Questionnaire with 10 personality disorder subjects with low scores on the Childhood Trauma Questionnaire. Personality disorder subjects will be otherwise healthy, without comorbid depression, posttraumatic stress disorder, or substance abuse. The 20 personality disorder subjects will be compared with 10 normal healthy controls with respect to CSF CRF level. A relationship between HPA axis function and childhood maltreatment has been previously described in adults with PTSD or Major depression and in primate and non-primate animal models of emotional/physical neglect. In this study, we seek to: a) replicate the history of childhood trauma/CRF relationship in PD subjects using basal CSF sampling of CRF; b) extend the findings of our previous study by examining both female and male personality disorder subjects; c) extend the findings by examing ACTH response to oCRF Challenge; d) compare CSF CRF and ACTH response to oCRF challenge to healthy normal controls. PD subjects will be prospectively identified as having been exposed to high amounts of childhood maltreatment or low amounts using scores from the Childhood Trauma Questionnaire (CTQ).20 male and female personality disorder subjects stratified into high vs. low CTQ score responders and 10 healthy normal controls will be admitted to our General Clinical Research Center for both lumbar puncture for CSF CRF and oCRF challenge.If this study is able to establish a relationship between history of childhood trauma and altered CSF CRF level and CRF responsivity (elevated ACTH response to oCRF challenge) in personality disordered subjects, this would allow for further work exploring the relationship between childhood trauma, HPA axis function, and stress reactivity in personality disorder.

R03MH066888

2003-09-01

2005-08-31