Child maltreatment and HPA axis dysregulation: relationship to major depressive disorder and post traumatic stress disorder in females

Shea, Alison K.; Walsh, Christine A.; MacMillan, Harriet L.; Steiner, Meir

doi:10.1016/j.psyneuen.2004.07.001

Cited by 328 publications

(200 citation statements)

References 139 publications

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“…However, our additional analyses suggest that a comorbid MDD did not cause the observed differences. Third, although early life trauma has been shown to affect HPA axis functioning significantly, 58 and might there-fore also have its effect on glucocorticoid immunoregulation, we did not assess the contribution of early life trauma.…”

Section: Discussionmentioning

confidence: 99%

Leukocyte glucocorticoid receptor expression and immunoregulation in veterans with and without post-traumatic stress disorder

et al. 2007

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Post-traumatic stress disorder (PTSD) is associated with a dysregulation of the hypothalamus-pituitary-adrenal axis (HPA axis). In addition, there is evidence for altered glucocorticoid receptor (GR) expression and function in peripheral blood mononuclear cells. The aim of the present study was to differentiate between the effect of trauma exposure and PTSD on leukocyte GR expression and glucocorticoid immune regulation. Leukocyte GR binding characteristics and glucocorticoid sensitivity of immune activity, determined as the effect of dexamethasone (DEX) on in vitro cytokine release and T-cell proliferation, were compared between veterans with PTSD, traumatized veterans without PTSD and healthy controls. Leukocyte GR density was significantly lower in veterans with and without PTSD compared to healthy controls. DEX-induced inhibition of T-cell proliferation was significantly lower in PTSD compared to trauma and healthy controls. DEX-induced increase in lipopolysaccharidestimulated interleukin-10 was less pronounced in traumatized veterans with and without PTSD compared to healthy controls. No group differences were observed in the effect of DEX on other cytokines or in baseline immune activity, except for lower tumor necrosis factor-a production in PTSD patients compared to healthy controls. The results suggest that trauma exposure is sufficient to induce changes in GR binding characteristics, whereas resistance of T-cell proliferation to DEX only occurs in PTSD. DEX resistance of in vitro immune activity was not a general phenomenon, but was restricted to specific immune functions.

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Section: Discussionmentioning

confidence: 99%

Leukocyte glucocorticoid receptor expression and immunoregulation in veterans with and without post-traumatic stress disorder

et al. 2007

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“…This work has received attention among PTSD researchers because of the parallel findings in humans, which link hypothalamic-pituitary-adrenal axis dysregulation and childhood maltreatment with predisposition to PTSD (Binder et al, 2008;Shea et al, 2005;Yehuda and LeDoux, 2007). Specifically, Meaney's lab has shown that natural variations in maternal licking and grooming alter DNA methylation and the expression of the glucocorticoid receptor gene, and produce altered patterns of hypothalamic-pituitary-adrenal axis reactivity, anxiety, and cognitive function in adulthood (Francis and Meaney, 1999;Liu et al, 2000;Meaney and Szyf, 2005a;Weaver et al, 2002a;Weaver et al, 2002b;Zaharia et al, 1996).…”

Section: Epigenetic Mechanisms In Ptsdmentioning

confidence: 99%

Epigenetic Mechanisms in Learned Fear: Implications for PTSD

Zovkic

Sweatt

2012

Neuropsychopharmacol

172

111

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One of the most exciting discoveries in the learning and memory field in the past two decades is the observation that active regulation of gene expression is necessary for experience to trigger lasting functional and behavioral change, in a wide variety of species, including humans. Thus, as opposed to the traditional view of 'nature' (genes) being separate from 'nurture' (environment and experience), it is now clear that experience actively drives alterations in central nervous system (CNS) gene expression in an ongoing fashion, and that the resulting transcriptional changes are necessary for experience to trigger altered long-term behavior. In parallel over the past decade, epigenetic mechanisms, including regulation of chromatin structure and DNA methylation, have been shown to be potent regulators of gene transcription in the CNS. In this review, we describe data supporting the hypothesis that epigenetic molecular mechanisms, especially DNA methylation and demethylation, drive long-term behavioral change through active regulation of gene transcription in the CNS. Specifically, we propose that epigenetic molecular mechanisms underlie the formation and stabilization of context-and cue-triggered fear conditioning based in the hippocampus and amygdala, a conclusion reached in a wide variety of studies using laboratory animals. Given the relevance of cued and contextual fear conditioning to post-traumatic stress, by extension we propose that these mechanisms may contribute to post-traumatic stress disorder (PTSD) in humans. Moreover, we speculate that epigenetically based pharmacotherapy may provide a new avenue of drug treatment for PTSD-related cognitive and behavioral function.

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“…Beyond its long-established functional role in stress-induced endocrine, autonomic, and behavioral responses via action at the hypothalamic-pituitary-adrenal (HPA) axis, CRH supports anxiety, via widespread CRHcontaining neurons at extrahypothalamic sites, in particular in limbic structures (Makino et al 1994a;1994b). Dysregulation of CRH activity has been linked to anxiety and mood disorders (Carroll et al 1976;McEwen 2005;Shea et al 2005) and acute and chronic treatment with CRH in rodents results in potentiation of anxiety-like responses in a number of behavioral assays of anxiety (Adamec and McKay 1993;Diamant et al 1992;Sherman and Kalin 1988). In contrast, CRH antagonists abolish stress-induced potentiation of anxiety (Korte and De Boer 2003).…”

Section: Preclinical Evidence For Dissociated Neural Systems Of Fear mentioning

confidence: 99%

Models and mechanisms of anxiety: evidence from startle studies

2007

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Rationale-Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by avoidance or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety).Objective-To 1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, 2) describe experimental models of anxiety, as opposed to fear, in humans, 3) examine the relevance of these models to clinical anxiety.Results-The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to nonphobic anxiety disorders.Conclusions-Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat.

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Child maltreatment and HPA axis dysregulation: relationship to major depressive disorder and post traumatic stress disorder in females

Cited by 328 publications

References 139 publications

Leukocyte glucocorticoid receptor expression and immunoregulation in veterans with and without post-traumatic stress disorder

Leukocyte glucocorticoid receptor expression and immunoregulation in veterans with and without post-traumatic stress disorder

Epigenetic Mechanisms in Learned Fear: Implications for PTSD

Models and mechanisms of anxiety: evidence from startle studies

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