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Cited by 78Posttraumatic Stress Disorder ResearchRedox biology and oxidative stressAntioxidant Activity and Oxidative Stress

Oxidative Dysregulation in Early Life Stress and Posttraumatic Stress Disorder: A Comprehensive Review

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Karanikas, Evangelos, Daskalakis, Nikolaos P., Agorastos, Agorastos·2021·Brain Sciences
DOI 10.3390/brainsci11060723PMC PMC8228973
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Abstract

Traumatic stress may chronically affect master homeostatic systems at the crossroads of peripheral and central susceptibility pathways and lead to the biological embedment of trauma-related allostatic trajectories through neurobiological alterations even decades later. Lately, there has been an exponential knowledge growth concerning the effect of traumatic stress on oxidative components and redox-state homeostasis. This extensive review encompasses a detailed description of the oxidative cascade components along with their physiological and pathophysiological functions and a systematic presentation of both preclinical and clinical, genetic and epigenetic human findings on trauma-related oxidative stress (OXS), followed by a substantial synthesis of the involved oxidative cascades into specific and functional, trauma-related pathways. The bulk of the evidence suggests an imbalance of pro-/anti-oxidative mechanisms under conditions of traumatic stress, respectively leading to a systemic oxidative dysregulation accompanied by toxic oxidation byproducts. Yet, there is substantial heterogeneity in findings probably relative to confounding, trauma-related parameters, as well as to the equivocal directionality of not only the involved oxidative mechanisms but other homeostatic ones. Accordingly, we also discuss the trauma-related OXS findings within the broader spectrum of systemic interactions with other major influencing systems, such as inflammation, the hypothalamic-pituitary-adrenal axis, and the circadian system. We intend to demonstrate the inherent complexity of all the systems involved, but also put forth associated caveats in the implementation and interpretation of OXS findings in trauma-related research and promote their comprehension within a broader context.

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  • Inflammation is involved in oxidative pathways and is a vital mechanism of oxidative stress generation and neurodegeneration in the periphery and the central nervous system.

    “Inflammation is additionally involved in oxidative pathways and is a vital mechanism of oxidative stress generation and neurodegeneration in the periphery and the central nervous system, in particular in stress-related disorders [17].”

    From Immune Cell Ratios Are Higher in Bipolar Affective than Unipolar Depressive Disorder and Modulated by Mood Episode: A Retrospective, Cross-Sectional Study (2023) · cites this paper as [17]

    Section 4.1, “Inflammation-Induced OXS” (page unavailable), explicitly calls inflammation a vital mechanism of oxidative-stress generation, particularly in stress-related disorders, and describes inflammatory signaling in peripheral and neuronal tissue. Section 2.3 links oxidative stress to neurodegenerative diseases, but the cited passages do not establish that inflammation is a vital mechanism of neurodegeneration in both the periphery and central nervous system. (LLM, conf=0.84)

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Authors
Karanikas, E., Daskalakis, N. P., & Agorastos, A.
Affiliations
  • Aristotle University of Thessaloniki (GR)
  • Harvard University (US)
Corresponding author
Agorastos, Agorastos
ORCID
Venue
Brain Sciences
Publisher
MDPI AG
Published
2021-05-29
Volume
11
Issue
6
Pages
723
ISSN
2076-3425 (ISSN-L)
DOI
10.3390/brainsci11060723
PMC
PMC8228973
OpenAlex
W3165680026
Cited by
78
References
295
Citations by year
2026: 11 · 2025: 16 · 2024: 18 · 2023: 17 · 2022: 13 · 2021: 3
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
oxidative stress, early life stress, post-traumatic stress disorder, traumatic stress, redox homeostasis, epigenetics, inflammation, hypothalamic-pituitary-adrenal axis, circadian system

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