Hydrocortisone administration for reducing post-traumatic stress symptoms: A systematic review and meta-analysis

Kothgassner, Oswald D.; Pellegrini, Marie; Goreis, Andreas; Giordano, Vito; Edobor, Joy; Fischer, Susanne; Plener, Paul L.; Huscsava, Mercedes

doi:10.1016/j.psyneuen.2021.105168

Cited by 25 publications

(17 citation statements)

References 38 publications

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“…We hypothesized that insufficient contextualization of neutral trauma-related information, possibly due to a blunted HPA-axis response and hence impaired development of slow corticosteroid actions, is a predisposing trait for PTSD. This hypothesis is supported by indirect evidence which shows that cortisol administration after trauma reduced vulnerability to PTSD (Kothgassner et al, 2021;Matar et al, 2013;Schelling et al, 2004). We only partly confirmed this notion.…”

Section: The Predictive Values Of Memory Contextualization For Ptsd-like Behaviorsupporting

confidence: 75%

Pre-trauma memory contextualization as predictor for PTSD-like behavior in male rats

Sep

Sarabdjitsingh

Geuze

et al. 2021

Preprint

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While many people experience potentially threatening events during their life, only a minority develops posttraumatic stress disorder (PTSD). The identification of individuals at risk among those exposed to trauma is crucial for PTSD prevention in the future. Since re-experiencing trauma elements outside of the original trauma-context is a core feature of PTSD, we investigate if the ability to bind memories to their original encoding context (i.e. memory contextualisation) predicts PTSD vulnerability. We hypothesize that pre-trauma neutral memory contextualization (under stress) negatively relates to PTSD-like behavior, in a prospective design using the cut-off behavioral criteria rat model for PTSD. 72 male Sprague Dawley rats were divided in two experimental groups to assess the predictive value of 1) memory contextualization without acute stress (NS-group) and 2) memory contextualization during the recovery phase of the acute stress-response (S-group) for susceptibility to PTSD-like behavior. A powerful extension to regression analysis -path analysis- was used to test this specific hypothesis, together with secondary research questions. Following traumatic predator scent stress, 19.4% of the rats displayed PTSD-like behavior. Results showed a negative relation between pre-trauma memory contextualization and PTSD-like behavior, but only in the NS-group. Pre-trauma memory contextualization was positively related to fear association in the trauma environment, again only in the NS group. If the predictive value of pre-trauma contextualization of neutral information under non-stressful conditions for PTSD susceptibility is replicated in prospective studies in humans, this factor would supplement already known vulnerability factors for PTSD and improve the identification of individuals at risk among the trauma exposed, especially those at high trauma risk such as soldiers deployed on a mission.

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Section: The Predictive Values Of Memory Contextualization For Ptsd-like Behaviorsupporting

confidence: 75%

Pre-trauma memory contextualization as predictor for PTSD-like behavior in male rats

Sep

Sarabdjitsingh

Geuze

et al. 2021

Preprint

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“…In the same individuals, a failure of cortisol to inhibit the retrieval of fear memories may then contribute to chronic re-experiencing of traumatic situations (e.g., via flashbacks). Indeed, the administration of hydrocortisone, a synthetic analogue of cortisol, has been found to reduce PTSD symptoms and incidence when administered in a preventive context (Kothgassner et al 2021 ). Furthermore, in individuals with PTSD, negative associations of cortisol with symptoms of intrusion, as well as with symptoms of avoidance, numbing, and hyper-arousal, have repeatedly been reported (Castro-Vale et al 2016 ).…”

Section: Hypothalamic–pituitary–adrenal Axis Functioningmentioning

confidence: 99%

Genes and hormones of the hypothalamic–pituitary–adrenal axis in post-traumatic stress disorder. What is their role in symptom expression and treatment response?

et al. 2021

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Background Less than half of all individuals with post-traumatic stress disorder (PTSD) remit spontaneously and a large proportion of those seeking treatment do not respond sufficiently. This suggests that there may be subgroups of individuals who are in need of augmentative or alternative treatments. One of the most frequent pathophysiological findings in PTSD is alterations in the hypothalamic–pituitary–adrenal (HPA) axis, including enhanced negative feedback sensitivity and attenuated peripheral cortisol. Given the role of the HPA axis in cognition, this pattern may contribute to PTSD symptoms and interfere with key processes of standard first-line treatments, such as trauma-focused cognitive behavioural therapy (TF-CBT). Methods This review provides a comprehensive summary of the current state of research regarding the role of HPA axis functioning in PTSD symptoms and treatment. Results Overall, there is preliminary evidence that hypocortisolaemia contributes to symptom manifestation in PTSD; that it predicts non-responses to TF-CBT; and that it is subject to change in parallel with positive treatment trajectories. Moreover, there is evidence that genetic and epigenetic alterations within the genes NR3C1 and FKBP5 are associated with this hypocortisolaemic pattern and that some of these alterations change as symptoms improve over the course of treatment. Conclusions Future research priorities include investigations into the role of the HPA axis in day-to-day symptom variation, the time scale in which biological changes in response to treatment occur, and the effects of sex. Furthermore, before conceiving augmentative or alternative treatments that target the described mechanisms, multilevel studies are warranted.

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“…While this relationship is consistent with the notion that HPA axis-induced secretion of cortisol inhibits the pro-inflammatory immune response via glucocorticoid negative feedback, 12,13 previous studies have shown that the inability to mount a cortisol response to traumatic stress exposure is predictive of greater PTSD risk. 41,42 The current data suggest that mounting an inflammatory response to traumatic stress is protective against PTSD development, 39 and indicates that individual-specific factors that influence this response, including steroid hormones, should be considered when determining the efficacy of pharmacological early interventions, such as hydrocortisone, 22 in attenuating prospective risk for PTSD development. This notion is further supported by the current data describing sex differences in steroid hormone levels and their relationships to pro-inflammatory markers in the acute aftermath of traumatic stress exposure.…”

Section: Discussionmentioning

confidence: 92%

“…These results were unexpected, as cortisol, progesterone, and testosterone have all been shown to modulate the immune system activity and inflammation 6 , 11 – 13 and have been implicated in the etiology and maintenance of PTSD. 13 – 16 , 22 An important caveat however is that most research on these steroid hormones to date have focused on their contribution to symptoms of the PTSD disease state rather than their contribution to prospective risk at the time of trauma. 53 Additionally, this research has historically been conducted in a sex-specific manner where steroids typically categorized as sex steroids for females (estradiol and progesterone) have not been extensively studied in males, and vice versa regarding testosterone levels in females.…”

Section: Discussionmentioning

confidence: 99%

“…For example, men have higher basal salivary cortisol concentrations than women, whereas women have a larger salivary cortisol response after experimental stress. 18 Furthermore, sex differences in other steroid hormones, including progesterone and testosterone, have previously been implicated in PTSD risk 16 , 22 and can modulate immune system activity 5 and the HPA axis. 23 Similar to cortisol, these other steroid hormones, predominantly, but not exclusively, made in the gonads, may also impact risk for PTSD by influencing the expression of inflammatory cytokines in response to trauma exposure.…”

Section: Introductionmentioning

confidence: 99%

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Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder

et al. 2021

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Women are at higher risk for developing posttraumatic stress disorder (PTSD) compared to men, yet little is known about the biological contributors to this sex difference. One possible mechanism is differential immunological and neuroendocrine responses to traumatic stress exposure. In the current prospective study, we aimed to identify whether sex is indirectly associated with the probability of developing nonremitting PTSD through pro-inflammatory markers and whether steroid hormone concentrations influence this effect. Female ( n = 179) and male ( n = 197) trauma survivors were recruited from an emergency department and completed clinical assessment within 24 h and blood samples within ∼three hours of trauma exposure. Pro-inflammatory cytokines (IL-6, IL-1[Formula: see text], TNF, IFNγ), and steroid hormone (estradiol, testosterone, progesterone, cortisol) concentrations were quantified in plasma. Compared to men, women had a higher probability of developing nonremitting PTSD after trauma ( p = 0.04), had lower pro-inflammatory cytokines and testosterone ( p’ s<0.001), and had higher cortisol and progesterone ( p’ s<0.001) concentrations. Estradiol concentrations were not different between the sexes ( p = 0.24). Pro-inflammatory cytokines were a significant mediator in the relationship between sex and probability of developing nonremitting PTSD ( p < 0.05), such that men had higher concentrations of pro-inflammatory cytokines which were associated with lower risk of nonremitting PTSD development. This effect was significantly moderated by estradiol ( p < 0.05), as higher estradiol levels in men were associated with higher pro-inflammatory cytokine concentrations and lower risk for developing nonremitting PTSD. The current results suggest that sex differences in the pro-inflammatory cytokine response to trauma exposure partially mediate the probability of developing nonremitting PTSD, and that the protective ability to mount an pro-inflammatory cytokine response in men may depend on higher estradiol levels in the aftermath of trauma exposure.

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Hydrocortisone administration for reducing post-traumatic stress symptoms: A systematic review and meta-analysis

Cited by 25 publications

References 38 publications

Pre-trauma memory contextualization as predictor for PTSD-like behavior in male rats

Pre-trauma memory contextualization as predictor for PTSD-like behavior in male rats

Genes and hormones of the hypothalamic–pituitary–adrenal axis in post-traumatic stress disorder. What is their role in symptom expression and treatment response?

Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder

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