
==== Front
Curr Neuropharmacol
Curr Neuropharmacol
CN
Current Neuropharmacology
1570-159X
1875-6190
Bentham Science Publishers

38284340
CN-22-522
10.2174/1570159X2204231106143917
Medicine, Neurology, Pharmacology, Neuroscience
Thematic Selection: Stress and Stress-related Disorders Posttraumatic Stress Disorder (Part 2)
Agorastos Agorastos 1*
1 Assistant Professor of Psychiatry, Aristotle University of Thessaloniki, Greece
* E-mail: aagorast@auth.gr
06 11 2023
2024
22 4 522523
© 2024 The Author(s). Published by Bentham Science Publishers
2024
The Author(s)
https://creativecommons.org/licenses/by/4.0/ © 2024 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode.
==== Body
pmcThe history of humanity is marked by violence, abuse, war and disasters, all of which have had a devastating impact of trauma on individuals, families, communities and societies. From a philosophical standpoint, trauma illuminates a deep existential dilemma between human fragility and resilience, health and disease, and the quality of life and death. Psychological and physical consequences of trauma have been reported from mankind’s first Epic of Gilgamesh to Homer’s Iliad, while several terms have been coined to describe them (e.g., cardiorespiratory neurosis, railway spine, shell shock, war neurosis, soldier’s heart, post-Vietnam syndrome, etc.) [1]. In 1952, DSM-I proceeded to the formulation of the diagnostic category “gross stress reaction” for the symptom cluster seen after a traumatic event and in 1980, DSM-III adopted, for the first time, the term posttraumatic stress disorder (PTSD) after the increasingly diagnosed posttraumatic symptoms in the Vietnam veterans [1].

PTSD is a chronic and debilitating condition of relatively high lifetime prevalence and disease burden that manifests in the aftermath of one or more profoundly traumatic or life-threatening experiences [2-4]. The diagnosis of PTSD requires at least one month of symptoms (Criterion F) following exposure to an actual, threatened or witnessed major traumatic event outside the range of usual human experience (Criterion A) [5, 6]. Typical signs include reexperiencing/intrusion symptoms (Criterion B), avoidance behaviors (Criterion C), cognitive and emotional symptoms (Criterion D), increased arousal and physiologic symptoms (Criterion E) and functional impairment (Criterion G). PTSD, however, exhibits distinct clinical phenotypes such as classic, dissociative, and complex presentations. It also displays variations in the timing of onset, along with diverse quantitative and qualitative course developments. Frequently, it includes nonspecific subsyndromal symptoms or overlapping symptoms with other diagnostic categories like depression, anxiety disorders, and insomnia. Thereby, individual susceptibility or resilience factors (e.g., personality traits, attachment style, support system, self-efficacy, marital and occupational status), as well as other trauma-related characteristics (e.g., severity, type of trauma, time of day), peritraumatic reactions, but also the history of repeated or continuous exposure can influence the individual development of traumatic sequalae at clinical level [3, 7-9].

Traumatic stress exposure has been proven to lead to sustained alterations in stress regulation and psychophysiological reactivity, impaired glucocorticoid signaling, changes in hypothalamic–pituitary–adrenal axis and sympathetic–adrenal–medullary system, as well as to epigenetic modifications [9, 10]. This can gradually affect master homeostatic systems at the crossroads of peripheral and central susceptibility pathways, leading to the biological embedment of the traumatic stress through neurobiological alterations with profound, cumulative and debilitating effects for health, overall disease vulnerability, physical and mental co-morbidity, as well as all-cause mortality even decades later [9, 11-17].

This current issue (Part 2) of the special thematic selection entitled “Stress and stress-related disorders” offers a comprehensive collection of articles on PTSD from molecular pathophysiology to cutting edge treatments.

With their article, Antolasic et al. review theoretical underpinnings of the involvement of BDNF and the Val66Met polymorphism in the development and persistence of intrusive and hypervigilance symptoms in PTSD [18]. Patas et al. provide a novel take on immune and inflammatory findings in PTSD and offer some stimulating ideas on immune-based PTSD treatment alternatives [19]. The article by Sabé et al. embodies a large scientometric analysis of 42,170 publications published between 1945 and 2022 to outline different aspects of clinical research in PTSD [20], while Lappas et al. offer a detailed review of available literature on the effect of antidepressants on sleep in patients with PTSD [21]. Finally, this special issue includes two seminal articles by two world-expert research groups in PTSD. The first paper by Burback et al. comes from Professor Vermetten’s research group in Leiden NL, and offers a very large, state-of-the-art comprehensive review on pharmacological, psychotherapeutic, behavioral and technology-related treatment of PTSD, which also initially provides an expert overview on symptomology, diagnostic issues, neurobiology and risk factors of PTSD and includes almost 1,000 references [22]. The second seminal paper by Zaretsky et al. comes from Professor Yehuda’s research group at Mount Sinai in New York, USA, and offers a state-of-the-art comprehensive review on the data supporting the current and future use of psychedelics in the treatment of PTSD while also presenting history of use, pharmacology and safety profile of all reviewed substances and includes almost 900 references [23].

In reflecting upon the profound research, clinical, individual and societal challenges of PTSD, one can only note an urgent current need to deepen our understandingof the neurobiological trajectories of PTSD development and course towards a chronic systematic disease continuum model and, herewith, better provide established treatments and also recognize new potentials for patients in need according to individual symptoms and risk/resilience factors.
==== Refs
REFERENCES

1 Crocq M.A. Crocq L. From shell shock and war neurosis to posttraumatic stress disorder: a history of psychotraumatology. Dialogues Clin. Neurosci. 2000 2 1 47 55 10.31887/DCNS.2000.2.1/macrocq 22033462
2 Yehuda R. Post-traumatic stress disorder. N. Engl. J. Med. 2002 346 2 108 114 10.1056/NEJMra012941 11784878
3 Yehuda R. Hoge C.W. McFarlane A.C. Vermetten E. Lanius R.A. Nievergelt C.M. Hobfoll S.E. Koenen K.C. Neylan T.C. Hyman S.E. Post-traumatic stress disorder. Nat. Rev. Dis. Primers 2015 1 1 15057 10.1038/nrdp.2015.57 27189040
4 Kessler R.C. Posttraumatic stress disorder: the burden to the individual and to society. J. Clin. Psychiatry 2000 61 Suppl. 5 4 12 10761674
5 American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. 5th Ed. Washington, DC 2013
6 (WHO) WHO International Classification of Diseases, Eleventh Revision (ICD-11) 2019
7 Murrough J.W. Russo S.J. The Neurobiology of Resilience: Complexity and Hope. Biol. Psychiatry 2019 86 6 406 409 10.1016/j.biopsych.2019.07.016 31466560
8 Hodes G.E. Epperson C.N. Sex differences in vulnerability and resilience to stress across the life span. Biol. Psychiatry 2019 86 6 421 432 10.1016/j.biopsych.2019.04.028 31221426
9 Agorastos A. Pervanidou P. Chrousos G.P. Baker D.G. Developmental trajectories of early life stress and trauma: A narrative review on neurobiological aspects beyond stress system dysregulation. Front. Psychiatry 2019 10 118 10.3389/fpsyt.2019.00118 30914979
10 Heim C. Nemeroff C.B. Neurobiology of posttraumatic stress disorder. CNS Spectr. 2009 14 1 Suppl. 1 13 24 19169190
11 Agorastos A. Pervanidou P. Chrousos G.P. Kolaitis G. Early life stress and trauma: developmental neuroendocrine aspects of prolonged stress system dysregulation. Hormones (Athens) 2018 17 4 507 520 10.1007/s42000-018-0065-x 30280316
12 Frodl T. O’Keane V. How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans. Neurobiol. Dis. 2013 52 24 37 10.1016/j.nbd.2012.03.012 22426398
13 Heim C. Nemeroff C.B. The impact of early adverse experiences on brain systems involved in the pathophysiology of anxiety and affective disorders. Biol. Psychiatry 1999 46 11 1509 1522 10.1016/S0006-3223(99)00224-3 10599479
14 Lupien S.J. McEwen B.S. Gunnar M.R. Heim C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat. Rev. Neurosci. 2009 10 6 434 445 10.1038/nrn2639 19401723
15 McEwen B.S. Protective and damaging effects of stress mediators. N. Engl. J. Med. 1998 338 3 171 179 10.1056/NEJM199801153380307 9428819
16 McEwen B.S. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol. Rev. 2007 87 3 873 904 10.1152/physrev.00041.2006 17615391
17 Agorastos A. Chrousos G.P. The neuroendocrinology of stress: the stress-related continuum of chronic disease development. Mol. Psychiatry 2022 27 1 502 513 10.1038/s41380-021-01224-9 34290370
18 Antolasic E.J. Jaehne E.J. Buuse M. Interaction of brain-derived neurotrophic factor, exercise, and fear extinction: Implications for post-traumatic stress disorder. Curr. Neuropharmacol. 2024 22 4 543 556 10.2174/1570159X21666230724101321 37491857
19 Patas K. Baker D.G. Chrousos G.P. Agorastos A. Inflammation in posttraumatic stress disorder: Dysregulation or recalibration? Curr. Neuropharmacol. 2024 22 4 524 542 37550908
20 Sabé M. Chen C. El-Hage W. Kaiser S. Leroy A. Vaiva G. Monari S. Premand N. Bartolomei J. Caiolo S. Maercker A. Pietrzak R.H. Cloître M. Solmi M. Half a century of research on posttraumatic stress disorder: A scientometric analysis. Curr. Neuropharmacol. 2024 22 4 736 748 10.2174/1570159X22666230927143106 37888890
21 Lappas A.S. Polyzopoulou Z.A. Christodoulou N. Bozikas V.P. Samara M.T. Effects of antidepressants on sleep in post-traumatic stress disorder: An overview of reviews. Curr. Neuropharmacol. 2024 22 4 749 805 37533247
22 Burback L. Brémault-Phillips S. Nijdam M.J. McFarlane A. Vermetten E. Treatment of posttraumatic stress disorder: A state-of-the-art review. Curr. Neuropharmacol. 2024 22 4 557 635 10.2174/1570159X21666230428091433 37132142
23 Zaretsky T.G. Jagodnik K. Barsic R. Antonio J.H. Bonanno P.A. Pierce C. The psychedelic future of post-traumatic stress disorder treatment. Curr. Neuropharmacol. 2024 22 4 636 735 38284341
