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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Available from: Royce Lee, Oct 02, 2015
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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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    ABSTRACT: The normal function of the hypothalamic-pituitary-adrenal (HPA) axis, and resultant glucocorticoid (GC) secretion, is essential for human health. Disruption of GC regulation is associated with both pathologic, psychological and physiological disease states such as depression, post-traumatic stress disorder, hypertension, diabetes, and osteopenia, amongst others. As such, understanding the mechanisms by which HPA output is tightly regulated in its responses to environmental stressors and circadian cues has been an active area of investigation for decades. Over the last 20 years, however, advances in gene targeting and genome modification in rodent models has allowed the detailed dissection of roles for key molecular mediators and brain regions responsible for this control in vivo to emerge. Here, we summarize work done to elucidate the function of critical neuropeptide systems, GC-signaling targets, and inflammation-associated pathways in HPA axis regulation and behavior, and highlight areas for future investigation.Neuropsychopharmacology accepted article preview online, 20 July 2015. doi:10.1038/npp.2015.215.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 07/2015; DOI:10.1038/npp.2015.215 · 7.05 Impact Factor
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    • "First, we measured total cortisol output from baseline through the post stress period by calculating area under the curve with respect to ground (AUCg; Pruessner et al. 2003) which represents the combined effect of the response to the stressor and declining cortisol levels due to the diurnal cycle. Second, we measured reactivity to the stress task via peak change in cortisol relative to baseline (PC) (Lee et al. 2012; Ramsay and Lewis 2003; Stroud, Papandonatos, Williamson, & Dahl). The primary analyses included two hierarchical linear regressions to examine the interactive effects of gender and cortisol (PC and AUCg in separate regressions) on RT-Stress. "
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    ABSTRACT: The purpose of this study was to evaluate how psychological stress, gender and cortisol response to stress relate to risk behavior among 132 14-18 year old adolescents. Participants completed a laboratory based risk task prior to and immediately after a computerized psychological stress task, and salivary cortisol was collected from pre-stress to 60 min following initial stress exposure. Results indicate that adolescent boys (n = 59) and girls (n = 73) demonstrate different patterns of risk taking (RT) in response to stress, such that boys evidenced an increase in RT following stress exposure, whereas girls evidenced a decrease in RT. In addition, a gender by cortisol interaction demonstrated that for boys, both a smaller total cortisol output (AUCg) and peak cortisol response to stress (PC) was associated with greater stress-induced RT. Both cortisol measures were unrelated to stress-induced RT among girls. Taken together, data suggest that among boys, a blunted cortisol response to stress underlies an increase in risk taking in the context of psychological stress. Further research with an additional behavioral stress task is needed prior to drawing conclusions regarding the relation between female gender, cortisol response to stress, and risk taking in the context of psychological stress.
    Journal of Abnormal Child Psychology 01/2013; 41(5). DOI:10.1007/s10802-013-9713-4 · 3.09 Impact Factor
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    ABSTRACT: Corticotropin-releasing hormone (CRH) in cerebrospinal fluid (CSF) is regarded as index of brain endocrine and behavioral functioning. We investigated the acute effects of intravenous cortisol (100mg) vs. placebo on serial CSF CRH in ten healthy men. CSF CRH concentrations were not significantly suppressed by cortisol within 3h. The origin and regulation of CSF CRH need further research.
    07/2013; 210(2). DOI:10.1016/j.psychres.2013.07.003
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