Low Estradiol Levels: A Vulnerability Factor for the Development of Posttraumatic Stress Disorder

Department of Psychiatry, Massachusetts General Hospital Harvard Medical School, Charlestown, USA.
Biological psychiatry (Impact Factor: 10.26). 07/2012; 72(1):6-7. DOI: 10.1016/j.biopsych.2012.04.029
Source: PubMed
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    • "Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that develops following exposure to psychological trauma (American Psychiatric Association [APA], 2013), with women facing higher risk for developing PTSD than men (Breslau & Anthony, 2007; Kessler, Sonnega, Bromet, Hughes, & Nelson, 1995; Olff, Langeland, Draijer, & Gersons, 2007; Tolin & Foa, 2006). Although the mechanisms underlying increased PTSD risk in women are not fully understood, research has identified the potential role of sexually dimorphic neurobiology in the stress systems of animals (Dalla & Shors, 2009; Graham & Milad, 2013; Milad, Igoe, Lebron- Milad, & Novales, 2009; Zeidan et al., 2011) and humans (Cahill, Uncapher, Kilpatrick, Alkire, & Turner, 2004; Goldstein, Jerram, Abbs, Whitfield-Gabrieli, & Makris, 2010; Goldstein et al., 2001; Graham & Milad, 2013; Lebron-Milad et al., 2012; Milad et al., 2006, 2010; Stevens et al., 2013). Recent work suggests that varying levels of female gonadal hormones, particularly estrogen, may influence fear extinction in women with PTSD (Glover et al., 2012; Lebron-Milad, Graham, & Milad, 2012). "
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    ABSTRACT: Recent research has found that individuals with posttraumatic stress disorder (PTSD) exhibit an impaired memory of fear extinction compounded by deficient functional activation of key nodes of the fear network including the amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (dACC). Research has shown these regions are sexually dimorphic and activate differentially in healthy men and women during fear learning tasks. To explore biological markers of sex differences following exposure to psychological trauma, we used a fear learning and extinction paradigm together with functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) to assess 31 individuals with PTSD (18 women; 13 men) and 25 matched trauma-exposed healthy control subjects (13 women; 12 men). Whereas no sex differences appeared within the trauma-exposed healthy control group, both psychophysiological and neural activation patterns within the PTSD group indicated deficient recall of extinction memory among men and not among women. Men with PTSD exhibited increased activation in the left rostral dACC during extinction recall compared with women with PTSD. These findings highlight the importance of tracking sex differences in fear extinction when characterizing the underlying neurobiological mechanisms of PTSD psychopathology.
    Full-text · Article · Sep 2014 · Neurobiology of Learning and Memory
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    ABSTRACT: An important feature of the human defense system comprises fear learning, which stress hormones can crucially modulate. However, stress hormones might influence men and women differently, in part because of interactions with sex hormones. In women, distinct stages of the menstrual cycle or the intake of oral contraceptives (OC) affect sex hormone levels. In this study, we used a differential fear conditioning paradigm with electrical stimulation as unconditioned stimulus (UCS) following one neutral stimulus (conditioned stimulus, CS+), but not another (CS-).To investigate implicit fear learning, participants were distracted from detecting the contingencies between CS and UCS. To address interaction effects of sex and stress hormones, 32 men, 30 women in the early follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU), and 30 OC women received either 30mg cortisol or a placebo. In the contrast CS+ minus CS-, an interaction between cortisol administration and sex hormone status emerged in the anterior parahippocampal gyrus and the hippocampus. Cortisol reduced fear learning in men, FO, and LU women, but enhanced it in OC women. Additionally, cortisol attenuated differential amygdala activation in the entire group. These results demonstrate that OC usage substantially modifies cortisol effects on emotional learning in women, particularly in memory-related medial temporal lobe regions. Further, a high dose of cortisol reduces amygdala differentiation pointing to a lowered learning ability of the defense system under high cortisol concentrations, irrespective of current sex hormone availability.
    No preview · Article · Sep 2012 · Hormones and Behavior
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    ABSTRACT: Extensive research has identified stereotypic behavioral and biological abnormalities in post-traumatic stress disorder (PTSD), such as heightened autonomic activity, an exaggerated startle response, reduced basal cortisol levels and cognitive impairments. We have reviewed primary research in this area, noting that factors involved in the susceptibility and expression of PTSD symptoms are more complex and heterogeneous than is commonly stated, with extensive findings which are inconsistent with the stereotypic behavioral and biological profile of the PTSD patient. A thorough assessment of the literature indicates that interactions among myriad susceptibility factors, including social support, early life stress, sex, age, peri- and post-traumatic dissociation, cognitive appraisal of trauma, neuroendocrine abnormalities and gene polymorphisms, in conjunction with the inconsistent expression of the disorder across studies, confounds attempts to characterize PTSD as a monolithic disorder. Overall, our assessment of the literature addresses the great challenge in developing a behavioral and biomarker-based diagnosis of PTSD.
    Full-text · Article · Apr 2013 · Neuroscience & Biobehavioral Reviews
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