Recent Progress in Understanding the Pathophysiology of Post-Traumatic Stress Disorder: Implications for Targeted Pharmacological Treatment
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Post-traumatic stress disorder (PTSD) is a common and chronic anxiety disorder that can result after exposure to a traumatic event. Though our understanding of the aetiology of PTSD is incomplete, several neurobiological systems have been implicated in the pathophysiology and vulnerability towards developing PTSD after trauma exposure. We aimed to provide a concise review of benchmark findings in important neurobiological systems related to the aetiology and maintenance of PTSD symptomology. Specifically, we discuss functional aetiologies in the noradrenergic, serotonergic, endogenous cannabinoid and opioid systems as well as the hypothalamic-pituitary adrenal (HPA) axis. This article provides a succinct framework to appreciate the current understanding of neurobiological mechanisms related to the pathophysiology of PTSD and how these findings may impact the development of future, targeted pharmacological treatments for this debilitating disorder.
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Other neuropeptides/neurotrophic factors, such as neuropeptide Y, dynorphin, oxytocin, and brain-derived neurotrophic factor (BDNF), are also involved in the HPA axis and in the orchestration of the response to stress.
“Other neuropeptides/neurotrophic factors, such as neuropeptide Y (95), dynorphin (96), and oxytocin as well as brain-derived neurotrophic factor (BDNF), are also involved in the HPA axis and in the orchestration of the response to stress.”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [96]
Section 6 (Opioid System; page unavailable) says the dynorphin/κ-opioid receptor system has a role in stress-induced behaviours, supporting the part of the sentence to which this paper appears to be cited. Section 5 (HPA Axis; page unavailable) discusses CRF and endocannabinoids, but does not link dynorphin to the HPA axis. Searches for neuropeptide Y, oxytocin, and BDNF did not find support for attributing those examples to this paper. (LLM, conf=0.84)
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Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma
Jiang, S., Postovit, L., Cattaneo, A., Binder, E. B., & Aitchison, K. J. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00808 · Cited by 288 · see citing works
“Other neuropeptides/neurotrophic factors, such as neuropeptide Y (95), dynorphin (96), and oxytocin as well as brain-derived neurotrophic factor (BDNF), are also involved in the HPA axis and in the orchestration of the response to stress.”
BackgroundMayo, L. M., Asratian, A., Lindé, J., Holm, L., Nätt, D., Augier, G., Stensson, N., Vecchiarelli, H. A., Balsevich, G., Aukema, R. J., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0215-1 · Cited by 166 · see citing works
PTSD: from neurobiology to pharmacological treatments
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Bowers, M. E., & Ressler, K. J. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.06.008 · Cited by 147 · see citing works
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Maladaptive autonomic regulation in PTSD accelerates physiological aging
Williamson, J. B., Porges, E. C., Lamb, D. G., & Porges, S. W. (2015) · Frontiers in Psychology · doi:10.3389/fpsyg.2014.01571 · Cited by 116 · see citing works
Effects of Cannabinoids on Sleep and their Therapeutic Potential for Sleep Disorders
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The endocannabinoid system in mental disorders: Evidence from human brain studies
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Neurocognition in PTSD: Treatment Insights and Implications
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Ketamine for post-traumatic stress disorders and it's possible therapeutic mechanism
Asim, M., Wang, B., Hao, B., & Wang, X. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.105044 · Cited by 37 · see citing works
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Traumatic Stress Produces Delayed Alterations of Synaptic Plasticity in Basolateral Amygdala
Zhang, H., Meng, S., Guo, X., Zhang, J., Zhang, W., Chen, Y., Lü, L., Yang, J., & Xue, Y.-X. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.02394 · Cited by 29 · see citing works
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Department of Psychological Medicine, K. C. L., Hussein, S., Himmerich, H., Department of Psychiatry, P. A. P., Willmund, G. D., Department of Psychiatry, P. A. P., Ibrahim, M. A. A., Department of Immunological Medicine and Allergy, K. H. P., Dalton, B., & Department of Psychological Medicine, K. C. L. (2017) · Psychiatria Danubina · doi:10.24869/psyd.2017.407 · Cited by 26 · see citing works
Augmenting the Treatment of PTSD with Ketamine—a Review
Duek, O. A., Kelmendi, B., Pietrzak, R. H., & Harpaz‐Rotem, I. (2019) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-019-00172-0 · Cited by 26 · see citing works
Elucidating Mental Health Disorders among Rohingya Refugees: A Malaysian Perspective
Kaur, K., Sulaiman, A. H., Yoon, C. K., Hashim, A. H., Kaur, M., Hui, K. O., Sabki, Z. A., Francis, B., Singh, S., & Gill, J. S. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17186730 · Cited by 27 · see citing works
Novel pharmacological treatment strategies for posttraumatic stress disorder
Thomas, E., & Stein, D. J. (2017) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2017.1260001 · Cited by 21 · see citing works
Müller, H., Czwalinna, K., Wang, R., Lücke, C., Lam, A. P., Philipsen, A., Gschossmann, J. M., & Moeller, S. (2021) · Psychiatric Quarterly · doi:10.1007/s11126-020-09873-9 · Cited by 22 · see citing works
Raise‐Abdullahi, P., Raeis-Abdollahi, E., Sameni, H., Vafaei, A. A., Ghanbari, A., & Rashidy‐Pour, A. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112867 · Cited by 21 · see citing works
Kelmendi, B., Adams, T. G., Southwick, S. M., Abdallah, C. G., & Krystal, J. H. (2017) · Clinical Psychology Science and Practice · doi:10.1111/cpsp.12202 · Cited by 20 · see citing works
Propranolol can induce PTSD ‐like memory impairments in rats
Zhu, R., Liu, X., Shi, Y., Wang, X., Xue, L., & Zhao, H. (2018) · Brain and Behavior · doi:10.1002/brb3.905 · Cited by 16 · see citing works
Using Virtual Reality to Explore Self-Regulation in High-Risk Settings
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Prajapati, S. K., Majumdar, S., Murari, S., MachhindraVadak, K., & Krishnamurthy, S. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5c00335 · Cited by 15 · see citing works
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Пивина, С. Г., Rakitskaya, V. V., Акулова, В. К., & Ordyan, N. E. (2016) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-016-3227-3 · Cited by 13 · see citing works
Bommaraju, S., Dhokne, M. D., Arun, E. V., Srinivasan, K., Sharma, S. S., & Datusalia, A. K. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.110943 · Cited by 12 · see citing works
Latimer, D. R., Stocker, M. D., Sayers, K., Green, J., Kaye, A. M., Abd-Elsayed, A. A., Cornett, E. M., Kaye, A. D., Varrassi, G., Viswanath, O., et al. (2025) · Psychopharmacology Bulletin · doi:10.64719/pb.4414 · Cited by 12 · see citing works
Medicinal Cannabis for the Treatment of Anxiety Disorders: a Narrative Review
Stack, S. K., Wheate, N., & Schubert, E. A. (2022) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-022-00260-8 · Cited by 13 · see citing works
Azevedo, H., Ferreira, M., Mascarello, A., Osten, P., & Guimarães, C. R. W. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107912 · Cited by 10 · see citing works
Anticonvulsants to treat post‐traumatic stress disorder
Wang, H. R., Woo, Y. S., & Bahk, W. (2014) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2425 · Cited by 12 · see citing works
Structural Plasticity and Molecular Markers in Hippocampus of Male Rats after Acute Stress
Chen, F., Polsinelli, B., Nava, N., Treccani, G., Elfving, B., Müller, H. K., Musazzi, L., Popoli, M., Nyengaard, J. R., & Wegener, G. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.05.001 · Cited by 9 · see citing works
Kingston, D. E., Mughal, M. K., Arshad, M., Kovalchuk, I., Metz, G. A. S., Wynne‐Edwards, K. E., King, S., Jiang, S., Postovit, L.-M. M., Wajid, A., et al. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00729 · Cited by 8 · see citing works
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Model systems for emulating human tissue and physiology in psychiatric research
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Prospective Relations Between Prenatal Maternal Cortisol and Child Health Outcomes
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Posttraumatic Stress Disorder and Its Effects on Men’s Sexual and Reproductive Health
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Management of post-traumatic stress disorder: a review of anxiety disorders and PTSD
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- Authors
- Bailey, C. R., Cordell, E., Sobin, S. M., & Neumeister, A.
- Affiliations
- Johns Hopkins University (US)
- NYU Langone Health (US)
- Corresponding author
- Neumeister, Alexander
- Venue
- CNS Drugs
- Published
- 2013-03
- Volume
- 27
- Issue
- 3
- Pages
- 221-232
- ISSN
- 1172-7047 (ISSN-L)
- 1179-1934
- PMC
- PMC3629370
- OpenAlex
- W2085725087
- Cited by
- 89
- References
- 203
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 10 · 2020: 9 · 2019: 9 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 7 · 2014: 7 · 2013: 2
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- CNS Drugs (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R21MH085627, R01MH096876, R21MH081103, R21MH096105)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
- Keywords
- post-traumatic stress disorder, pathophysiology, noradrenergic system, serotonergic system, endocannabinoid system, opioid system, hypothalamic-pituitary-adrenal axis, trauma exposure
- MeSH terms
- Animals, Female, Humans, Hypothalamo-Hypophyseal System, Male, Pituitary-Adrenal System, Stress Disorders, Post-Traumatic, Drug Design, Molecular Targeted Therapy
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