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Review
. 2022 Apr 20;10(5):953.
doi: 10.3390/biomedicines10050953.

Neuroinflammation in Post-Traumatic Stress Disorder

Dong-Hun Lee  1   2 , Ji-Young Lee  1 , Dong-Yong Hong  1   2 , Eun-Chae Lee  1   2 , Sang-Won Park  1   2 , Man-Ryul Lee  2 , Jae-Sang Oh  1   2
Affiliations
Review

Neuroinflammation in Post-Traumatic Stress Disorder

Dong-Hun Lee et al. Biomedicines. .

Abstract

Post-traumatic stress disorder (PTSD) is a well-known mental illness, which is caused by various stressors, including memories of past physical assaults and psychological pressure. It is diagnosed as a mental and behavioral disorder, but increasing evidence is linking it to the immune system and inflammatory response. Studies on the relationship between inflammation and PTSD revealed that patients with PTSD had increased levels of inflammatory cytokine biomarkers, such as interleukin-1, interleukin-6, tumor necrosis factor-α, nuclear factor-κB, and C-reactive protein, compared with healthy controls. In addition, animal model experiments imitating PTSD patients suggested the role of inflammation in the pathogenesis and pathophysiology of PTSD. In this review, we summarize the definition of PTSD and its association with increased inflammation, its mechanisms, and future predictable diseases and treatment possibilities. We also discuss anti-inflammatory treatments to address inflammation in PTSD.

Keywords: animal models; behavior test; damage-associated molecular patterns; hypothalamic-pituitary-adrenal axis; inflammation; kynurenine; neuroinflammation; post-traumatic stress disorder; serotonin; tryptophan.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Development of PTSD animal models. (A) Forced swimming; (B) ether is applied to the rodent model until it becomes unconscious; (C) electric shock through metal bar; (D) isolation from the parent herd; and (E) exposure to predators.
Figure 2
Figure 2
Mechanisms of increased inflammation in PTSD. The immune system interacts with the hypothalamus, pituitary, and adrenal axis. The black arrow represents a series of sequential processes, the red arrow represents the final result of neuroinflammation, and the dotted line represents inhibition according to the process. ACTH, adrenocorticotropin; AVP, arginine vasopressin; CRH, corticotropin-releasing hormone; GR, glucocorticoid receptor; NE, norepinephrine; NF-κB, nuclear factor-κB; IL, interleukin; TNF-α, tumor necrosis factor α.
Figure 3
Figure 3
Effect of inflammatory cytokines in PTSD. PTSD interferes with cytokine homeostasis and inhibits the secretion of anti-inflammatory cytokines through the activation of the HPA axis, SAM axis, and vagus nerves. Continuous PTSD can induce HPA fatigue and increase glucocorticoid receptors, inducing inflammatory reactions and causing neuroinflammation by crossing the BBB. HPA, hypothalamic–pituitary–adrenal; SAM, sympathetic–adrenal–medullary system.
Figure 4
Figure 4
The effect of reduced tryptophan on the kynurenine pathway, as well as various emotional–behavioral disorders caused by a decrease in serotonin levels due to reduced tryptophan. NMDA, N-methyl-d-aspartate.
See this image and copyright information in PMC

References

    1. Stein D.J., McLaughlin K.A., Koenen K.C., Atwoli L., Friedman M.J., Hill E.D., Maercker A., Petukhova M., Shahly V., van Ommeren M., et al. DSM-5 and ICD-11 Definitions of Posttraumatic Stress Disorder: Investigating “Narrow” and “Broad” Approaches. Depress. Anxiety. 2014;31:494–505. doi: 10.1002/da.22279. - DOI - PMC - PubMed
    1. Rosenfield P.J., Stratyner A., Tufekcioglu S., Karabell S., Mckelvey J., Litt L. Complex PTSD in ICD-11: A Case Report on a New Diagnosis. J. Psychiatr. Pract. 2018;24:364–370. doi: 10.1097/PRA.0000000000000327. - DOI - PubMed
    1. Iribarren J., Prolo P., Neagos N., Chiappelli F. Post-Traumatic Stress Disorder: Evidence-Based Research for the Third Millennium. Evid. Based Complement. Alternat. Med. 2005;2:503–512. doi: 10.1093/ecam/neh127. - DOI - PMC - PubMed
    1. Brewin C.R. A Cognitive Neuroscience Account of Posttraumatic Stress Disorder and its Treatment. Behav. Res. Ther. 2001;39:373–393. doi: 10.1016/S0005-7967(00)00087-5. - DOI - PubMed
    1. McNally R.J. Cognitive Abnormalities in Post-Traumatic Stress Disorder. Trends Cogn. Sci. 2006;10:271–277. doi: 10.1016/j.tics.2006.04.007. - DOI - PubMed