Gender differences in the effect of early life trauma on hypothalamic-pituitary-adrenal axis functioning

Department of Medicine, Division of Biostatistics and Epidemiology, Medical University of South Carolina, 135 Cannon Street, Charleston, SC 29425, USA.
Depression and Anxiety (Impact Factor: 4.41). 05/2011; 28(5):383-92. DOI: 10.1002/da.20795
Source: PubMed


The objective of this study was to examine the modifying effect of gender on the association between early life trauma and the hypothalamic-pituitary-adrenal (HPA) axis response to a pharmacologic challenge and a social stress task in men and women. Participants (16 men, 23 women) were the control sample of a larger study examining HPA axis function. Individuals with major depressive disorder, posttraumatic stress disorder, bipolar disorder, or psychotic or eating disorders were excluded.
In two test sessions, subjects received 1 µg/kg of corticotropin-releasing hormone (CRH) intravenously and participated in the Trier Social Stress Test (TSST). Primary outcomes included plasma cortisol and corticotropin levels measured at baseline and more than five time points following the challenges. Predictors included gender and early life trauma, as measured by the Early Trauma Index. Using factor analysis, the domains general trauma, severe trauma, and the effects of trauma were established. Using regression, these constructs were used to predict differential HPA reactivity in men and women following the challenges.
The three factors accounted for the majority of the variance in the ETI. Following the CRH challenge, women had higher overall corticotropin response as dictated by the area under the curve analysis. There were no significant associations between trauma and neuroendocrine response to the TSST.
CRH challenge results indicate that gender differences in the impact of early trauma may help explain the differential gender susceptibility to psychopathology following adverse childhood events. This may help explain gender differences in some stress-sensitive psychiatric disorders.

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Available from: Nathaniel L Baker, Oct 06, 2015
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    • "Although we cannot rule out the possibility that our androgen supplementation paradigms acted further up in the hypothalamo-pituitary–adrenal axis, it is unlikely that CRH or ACTH were affected because we saw no stimulatory effect of androgen on cortisol; like DHEA/S, cortisol is stimulated by ACTH but is secreted primarily from the zona fasicularis (ZF) rather than the ZR. Also, several studies suggest ACTH secretion is similar in males and females (30–33). Previous studies of post-menopausal women found that long-term administration of DHEA increased DHEA production in response to ACTH (34, 35), a finding we did not replicate presently as when DHEA was administered without testosterone we observed no night-time increase in circulating DHEAS. "
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    ABSTRACT: The adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are two of the most abundant hormones in the human circulation. Furthermore, they are released in a circadian pattern and show a marked age-associated decline. Adult levels of DHEA and DHEAS are significantly higher in males than in females, but the reason for this sexual dimorphism is unclear. In the present study, we administered supplementary androgens [DHEA, testosterone and 5α-dihydrotestosterone (DHT)] to aged male rhesus macaques (Macaca mulatta). While this paradigm increased circulating DHEAS immediately after DHEA administration, an increase was also observed following either testosterone or DHT administration, resulting in hormonal profiles resembling levels observed in young males in terms of both amplitude and circadian pattern. This stimulatory effect was limited to DHEAS, as an increase in circulating cortisol was not observed. Taken together, these data demonstrate an influence of the hypothalamo-pituitary-testicular axis on adrenal function in males, possibly by sensitizing the zona reticularis to the stimulating action of adrenocorticopic hormone. This represents a plausible mechanism to explain sex differences in circulating DHEA and DHEAS levels, and may have important implications in the development of hormone therapies designed for elderly men and women.
    Frontiers in Endocrinology 06/2014; 5:101. DOI:10.3389/fendo.2014.00101
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    • "In a recent study it has been shown that exposure to early trauma is positively associated with baseline corticotropin in women, whereas there was a negative association in men. In contrast, severe trauma was strongly positively associated with corticotropin response to CRH challenge in men but not in women (DeSantis et al., 2011). Furthermore, programming effects of pre- and postnatal maternal mood on sympathetic nervous system reactivity in response to physiological stressors appear to be restricted to males (Vedhara et al., 2012). "
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    ABSTRACT: Environmental influences such as perinatal stress have been shown to program the developing organism to adapt brain and behavioral functions to cope with daily life challenges. Evidence is now accumulating that the specific and individual effects of early life adversity on the functional development of brain and behavior emerge as a function of the type, intensity, timing and the duration of the adverse environment, and that early life stress (ELS) is a major risk factor for developing behavioral dysfunctions and mental disorders. Results from clinical as well as experimental studies in animal models support the hypothesis that ELS can induce functional "scars" in prefrontal and limbic brain areas, regions that are essential for emotional control, learning and memory functions. On the other hand, the concept of "stress inoculation" is emerging from more recent research, which revealed positive functional adaptations in response to ELS resulting in resilience against stress and other adversities later in life. Moreover, recent studies indicate that early life experiences and the resulting behavioral consequences can be transmitted to the next generation, leading to a transgenerational cycle of adverse or positive adaptations of brain function and behavior. In this review we propose a unifying view of stress vulnerability and resilience by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits. The adaptive maturation of stress responsive neural and endocrine systems requires environmental challenges to optimize their functions. Repeated environmental challenges can be viewed within the framework of the match/mismatch hypothesis, the outcome, psychopathology or resilience, depends on the respective predisposition and on the context later in life.
    Frontiers in Neuroscience 02/2014; 8(8):11. DOI:10.3389/fnins.2014.00011 · 3.66 Impact Factor
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    • "Most studies on PTSD and depression find higher both rates in women. Consistent with the dynamic diathesisstress model outlined above, models of these gender differences suggest that there are neuroendocrine and psychological consequences of prior exposure to sexual abuse that confer vulnerability to the psychopathogenic effects of subsequent trauma and stress (Cortina and Kubiak 2006; DeSantis et al. 2011; Harkness, Bruce, and Lumley 2006; Kendler, Kuhn, and Prescott 2004; Teicher et al. 2003; Weiss, Longhurst, and Mazure 1999). Female sex hormones (Olff et al. 2007; Parker and Brotchie 2010) and gendered socialization processes are also thought to augment female responsivity to trauma and to lead to less effective coping and greater sensitivity to lack of social support among women (Olff et al. 2007). "
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