Pharmacological modulation of acute trauma memories to prevent PTSD: Considerations from a developmental perspective

Abstract

Estimates of the lifetime prevalence of posttraumatic stress disorder (PTSD) in American adults range from 6.4–6.8%. PTSD is associated with increased risk for comorbid major depression, substance use disorder, suicide, and a variety of other mental and physical health conditions. Given the negative sequelae of trauma/PTSD, research has focused on identifying efficacious interventions that could be administered soon after a traumatic event to prevent or reduce the subsequent incidence of PTSD. While early psychosocial interventions have been shown to be relatively ineffective, early (secondary) pharmacological interventions have shown promise. These pharmacological approaches are largely based on the hypothesis that disruption of altered stress hormone levels and the consequent formation of trauma memories could protect against the development of PTSD. The present manuscript reviews the literature regarding the role of peri-traumatic stress hormones as risk factors for the development of PTSD and reviews evidence for the efficacy of exogenously modulating stress hormone levels to prevent/buffer the development of PTSD symptoms. Whereas prior literature has focused primarily on either child or adult studies, the present review incorporates both child and adult studies in a developmental approach to understanding risk for PTSD and how pharmacological modulation of acute memories may buffer the development of PTSD symptoms.

Cortisol, heart rate, and blood pressure as early markers of PTSD risk: A systematic review and meta-analysis

“…Prior reviews have noted that increased risk for developing PTSD is linked to higher circulating cortisol levels in children and lower circulating cortisol levels in adults (Delahanty & Nugent, 2006; Hruska et al, 2014; Morris & Rao, 2013; Pervanidou, 2008). The present findings extend these observations by identifying a developmental shift: higher cortisol levels were positively associated with PTSD symptoms in samples with a mean age less than 30 years and negatively associated with PTSD symptoms in samples with a mean age greater than 30 years.…”

“…There was early evidence that blocking this process by administering the beta receptor antagonist propranolol immediately after trauma exposure could reduce PTSD risk, but subsequent work has not supported its efficacy (see meta-analytic review by Sijbrandij, Kleiboer, Bisson, Barbui, & Cuipers, 2015). Timing may be critical, however, since there is a narrow consolidation window and these pharmacological intervention studies may not have administered propranolol soon enough to alter SNS-mediated memory consolidation processes (Hruska, Cullen, & Delahanty, 2014). The window of opportunity to alter (re)consolidation of memories appears to close within hours (McGaugh, 2000; Nader, Schafe, & LeDoux, 2000).…”

“…Psychosocial challenge studies have generally found elevated SNS reactivity in both trauma-exposed children (Kirsch et al, 2011; Saltzman, Holden, & Holahan, 2005) and adults (Liberzon, Anelson, Flagel, Raz, & Young, 1999) compared to non-exposed controls; however, findings regarding HPA reactivity in children have been equivocal (Gunnar, Frenn, Wewerka, & Van Ryzin, 2009; Ivanov et al, 2011). Age-related differences in the relation between peritraumatic cortisol levels and subsequent PTSD symptoms have been summarized in qualitative reviews; specifically, risk for PTSD has generally been linked to higher cortisol secretion in youth and lower cortisol secretion in adults (Delahanty & Nugent, 2006; Hruska et al, 2014; Morris & Rao, 2013). Unfortunately, it is impossible to parse the relative influence of developmental factors versus prior trauma exposure on neurobiological features of PTSD in child and adult survivors.…”

“…The timing of administration may nevertheless still be important and other negative studies that missed the window for targeting SNS-mediated memory consolidation processes (Hruska et al, 2014) may have compromised the meta-analytic results. Timing may be important in the contribution of SNS activity and its disruption to PTSD-risk and preventive interventions.…”

Hair cortisol concentrations and cortisol stress reactivity predict PTSD symptom increase after trauma exposure during military deployment

“…Given previous evidence suggesting beneficial effects of hydrocortisone administration immediately after trauma exposure for preventing the development of PTSD (reviewed in Hruska et al, 2014), future research should aim to examine whether pre-traumatic cortisol activity might modulate the efficacy of such hydrocortisone treatment.…”