Post-traumatic stress disorder: pathogenesis, epidemiological characteristics, animal models, and potential therapeutic strategies

Faith Nguyen; Ashok K. Shetty

doi:10.1016/j.mmr.2026.100005

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Post-traumatic stress disorder: pathogenesis, epidemiological characteristics, animal models, and potential therapeutic strategies

REVIEW | Updated：2026-05-11

- Post-traumatic stress disorder: pathogenesis, epidemiological characteristics, animal models, and potential therapeutic strategies
- Military Medical Research (2026)
- Affiliations：
  
  Institute for Regenerative Medicine, Department of Cell Biology and Genetics, Texas A&M University Naresh Vashisht College of Medicine, Bryan-College Station, 77807, Texas, USA
- Author bio：
  
  *Ashok K. Shetty, ash.shetty@tamu.edu
- Funds：
- DOI：10.1016/j.mmr.2026.100005
  CLC：
- Received：29 August 2025，
  
  Revised：2026-03-05，
  
  Published：2026-03
- Accepted：
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Nguyen F, Shetty AK. Post-traumatic stress disorder: pathogenesis, epidemiological characteristics, animal models, and potential therapeutic strategies. Mil Med Res.2026;13(1):100005.
DOI：

Nguyen F, Shetty AK. Post-traumatic stress disorder: pathogenesis, epidemiological characteristics, animal models, and potential therapeutic strategies. Mil Med Res.2026;13(1):100005. DOI： 10.1016/j.mmr.2026.100005.

摘要

Abstract

Post-traumatic stress disorder (PTSD) is a complex neurobehavioral disorder that disproportionately affects military service members. The clinical presentation of PTSD is heterogeneous and may overlap with other psychiatric conditions. According to the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)

common symptoms include memory loss

mood and personality changes

impulsiveness

aggression

anxiety

and depression. The pathophysiological mechanisms underlying PTSD remain incompletely understood

although research implicates pathways involving the hypothalamic-pituitary-adrenal (HPA) axis

dysfunctional neural circuitry

neurochemical imbalances

neuroinflammatory processes

and genetic and epigenetic factors. Approximately 7% of the U.S. adult population has met the diagnostic criteria for PTSD in their lifetime

with a substantially higher prevalence of 12%–30% among military personnel. Multiple animal models

including single-stressor

intermediate complexity

social interaction

predator stress

and blast exposure paradigms

have been employed to investigate PTSD mechanisms. Current treatment strategies typically integrate pharmacotherapy and psychotherapy. Military service members are at increased risk for blast injuries

which frequently result in traumatic brain injury (TBI). Although some symptoms of TBI may resolve

approximately 20% of affected individuals develop new symptoms

including PTSD. Evidence suggests that exposure to blast shock waves (BSWs) serves as a critical trigger for the clinical manifestations of both TBI and PTSD. Recent studies have identified several mechanisms contributing to BSW-induced brain dysfunction

including intraneuronal accumulation of phosphorylated Tau (p-Tau)

activation of the dynorphin/kappa opioid receptor

and activation of metabotropic glutamate receptor 2/3 signaling pathways. This review provides an overview of the clinical features

treatments

pathophysiology

and epidemiology of PTSD

as well as animal models and their limitations in replicating PTSD-like symptoms. It further examines the relationship between BSW exposure

brain injury

and PTSD

discusses animal models that simulate blast trauma and PTSD-like symptoms

and evaluates potential therapies to mitigate BSW-induced PTSD. Finally

the review addresses the limitations of current models and proposes future directions for elucidating the mechanisms linking brain trauma to PTSD.

关键词

Keywords

references

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