The neuroendocrinology of childhood trauma in personality disorder

The University of Chicago Medical Center, 5841 S. Maryland Ave, Chicago, IL 60637, USA.
Psychoneuroendocrinology (Impact Factor: 4.94). 06/2011; 37(1):78-86. DOI: 10.1016/j.psyneuen.2011.05.006
Source: PubMed


Childhood trauma has been associated with elevated central corticotropin releasing hormone (CRH) drive in adults meeting general DSM-IV criteria for personality disorder. It is not clear how this may be related to pituitary or adrenal responsiveness in personality disorder. It was hypothesized that high levels of childhood trauma would be associated with blunted cortisol and adrenocorticotropin releasing hormone (ACTH) response to the combined dexamethasone(DEX)/CRH test in adults meeting general DSM-IV criteria for personality disorder.
24 healthy, medication free adults with personality disorder (N=16) and a group of healthy controls (N=8) underwent semi-structured diagnostic interviews and completed the Childhood Trauma Questionnaire (CTQ). Across two separate study sessions separated by at least a week, cerebrospinal fluid (CSF) was sampled by lumbar puncture for measurement of CRH concentration (N=17), and peripheral blood cortisol and ACTH levels were measured after challenge with DEX/CRH (N=24).
As hypothesized, high CTQ score was associated with a blunted cortisol and ACTH response to DEX/CRH challenge. Indices of cortisol and ACTH response (peak level and area under the curve (AUC)) to DEX/CRH were in turn significantly negatively correlated with CSF CRH concentration.
Childhood trauma in adults with personality disorder is associated with blunted cortisol and ACTH secretion following DEX/CRH challenge. These effects are independent of depression or posttraumatic stress disorder. Previous work would suggest that blunted pituitary-adrenal response is related to elevated central CRH drive. Corroborating this, CSF CRH levels were significantly and negatively correlated with peak level and AUC of both cortisol and ACTH.

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    • "A principal function of increased CRH expression in human depression is demonstrated by both clinical and preclinical studies (Bartolomucci and Leopardi, 2009) studies. In depression, elevated concentrations of CRH can be found in the cerebrospinal fluid (Lee et al, 2012) and in the number of CRH expressing cells in the PVN (Raadsheer et al, 1994). On the contrary, a dulled ACTH response to CRH delivery has also been associated with depressive-like behavior (Heim et al, 2000). "
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