Translating Molecular and Neuroendocrine Findings in PTSD and Resilience to Novel Therapies
J. DePierro, Lauren Lepow, Adriana Feder, Rachel Yehuda
Biological Psychiatry July 24, 2019 DOI: 10.1016/j.biopsych.2019.07.009 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Critical review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | PTSD |
| Key findings | The authors argue that most pharmacologic approaches to PTSD target dysregulated adrenergic, HPA axis, and NPY systems, while ketamine and MDMA-assisted psychotherapy have emerged as promising but mechanistically unclear strategies. They propose that promoting resilience may require both pharmacological correction of dysregulated pathways and a substantial mental-state change that facilitates psychotherapeutic engagement with traumatic material. |
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 paper 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, the hypothalamic-pituitary-adrenal (HPA) axis, and neuropeptide Y (NPY) systems. Other highlighted approaches involve the use of ketamine and 3,4-methylenedioxymethamphetamine (MDMA)-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 post-traumatic symptoms. To the extent that use of ketamine and MDMA promote symptom improvement and resilience in PTSD, this provides an opportunity for reverse-translation and identification of relevant targets and mechanism 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.
Comparable studies
Other narrative reviews on PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic Psychiatry's Brave New World. | 2020 | Review | |
| Reviewing the Potential of Psychedelics for the Treatment of PTSD | 2020 | Review | |
| Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. | 2016 | Review | |
| MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? | 2018 | Review | |
| Clinical applications of hallucinogens: A review. | 2016 | Review |