Translating Molecular and Neuroendocrine Findings in Posttraumatic Stress Disorder and Resilience to Novel Therapies

Abstract

Many biological systems are altered in association with posttraumatic stress disorder (PTSD) and resilience. However, there are only few approved pharmacological treatments for PTSD, and no approved medications to enhance resilience. This article provides a critical review of select neurobiological findings in PTSD and resilience, and also of pharmacologic approaches that have emerged from this work. The medications summarized involve engagement with targets in the adrenergic, hypothalamic-pituitary-adrenal axis, and neuropeptide Y systems. Other highlighted approaches involve the use of ketamine and 3,4-methylenedioxymethamphetamine-assisted psychotherapy, which recently surfaced as promising strategies for PTSD, though the neurobiological mechanisms underlying their actions, including for promoting resilience, are not yet fully understood. The former approaches fall within the broad concept of "rational pharmacotherapy," in that they attempt to directly target dysregulated systems known to be associated with posttraumatic symptoms. To the extent that use of ketamine and 3,4-methylenedioxymethamphetamine promotes symptom improvement and resilience in PTSD, this provides an opportunity for reverse translation and identification of relevant targets and mechanisms of action through careful study of biological changes resulting from these interventions. Promoting resilience in trauma-exposed individuals may involve more than pharmacologically manipulating dysregulated molecules and pathways associated with developing and sustaining PTSD symptom severity, but also producing a substantial change in mental state that increases the ability to engage with traumatic material in psychotherapy. Neurobiological examination in the context of treatment studies may yield novel targets and promote a greater understanding of mechanisms of recovery from trauma.

Keywords: Glucocorticoids; Ketamine; MDMA; PTSD; Pharmacotherapy; Resilience.

Conflict of interest statement

Financial Disclosures

Dr. Feder is named co-inventor on a patent application in the US, and several issued patents outside the US filed by the Icahn School of Medicine at Mount Sinai related to the use of ketamine for the treatment of post-traumatic stress disorder (PTSD). This intellectual property has not been licensed. Dr. Yehuda is listed as co-inventor on a US patent pertaining to genetic testing in PTSD. Drs. DePierro and Lepow reported no biomedical financial interests or potential conflicts of interest.

Published by Elsevier Inc.