A SYSTEMATIC REVIEW OF TUMOR NECROSIS FACTOR-α IN POST-TRAUMATIC STRESS DISORDER: EVIDENCE FROM HUMAN AND ANIMAL STUDIES

Hussein, Serkan; Dalton, Bethan; Willmund, Gerd; Ibrahim, Merdol; Himmerich, Hubertus

doi:10.24869/psyd.2017.407

Cited by 21 publications

(18 citation statements)

References 30 publications

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“…It is important to note, however, that altered blood cytokine levels as discussed here are not specific for affective disorders, but have also been found elevated in post-traumatic stress disorders (PTSD) (58, 59), obsessive-compulsive disorders (OCD) (60) or eating disorders (61). Additionally, low grade inflammation and cytokine elevation play a role in a number of physical diseases for example metabolic diseases such as diabetes and obesity as hallmarks of the metabolic syndrome.…”

Section: Innate Immune Response In Depressionmentioning

confidence: 88%

Mitochondria, Microglia, and the Immune System—How Are They Linked in Affective Disorders?

et al. 2019

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Major depressive disorder (MDD) is a severe mood disorder and frequently associated with alterations of the immune system characterized by enhanced levels of circulating pro-inflammatory cytokines and microglia activation in the brain. Increasing evidence suggests that dysfunction of mitochondria may play a key role in the pathogenesis of MDD. Mitochondria are regulators of numerous cellular functions including energy metabolism, maintenance of redox and calcium homeostasis, and cell death and therefore modulate many facets of the innate immune response. In depression-like behavior of rodents, mitochondrial perturbation and release of mitochondrial components have been shown to boost cytokine production and neuroinflammation. On the other hand, pro-inflammatory cytokines may influence mitochondrial functions such as oxidative phosphorylation, production of adenosine triphosphate, and reactive oxygen species, thereby aggravating inflammation. There is strong interest in a better understanding of immunometabolic pathways in MDD that may serve as diagnostic markers and therapeutic targets. Here, we review the interaction between mitochondrial metabolism and innate immunity in the pathophysiology of MDD. We specifically focus on immunometabolic processes that govern microglial and peripheral myeloid cell functions, both cellular components involved in neuroinflammation in depression-like behavior. We finally discuss microglial polarization and associated metabolic states in depression-associated behavior and in MDD.

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Section: Innate Immune Response In Depressionmentioning

confidence: 88%

Mitochondria, Microglia, and the Immune System—How Are They Linked in Affective Disorders?

et al. 2019

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“…Cytokine TNF-α is regarded as a key inflammatory cytokine of the immune response, 26 but elevated levels of proinflammatory cytokines TNF-α and IL-1β have simultaneously been found in PTSD patients when compared to controls, 27 and it has been postulated that a combination of several elevated cytokines may be an indicator of PTSD. 26 We also found chemokine MCP-1 and cytokine IL-1β to increase over time in PTSD patients. It may be that increased TNF-α level accompanied by elevated IL-1β and MCP-1 could be viewed as biomarkers in PTSD.…”

Section: Discussionmentioning

confidence: 99%

PTSD patients show increasing cytokine levels during treatment despite reduced psychological distress

Toft¹,

Bramness²,

Lien³

et al. 2018

NDT

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BackgroundA reciprocal relationship between activated innate immune system and changes in mood and behavior has been established. There is still a paucity of knowledge on how the immune system responds during psychiatric treatment. We aimed to explore circulating cytokines and assess psychiatric symptom severity scores during 12 weeks of inpatient psychiatric treatment.MethodsThe study was a longitudinal assessment of 124 patients (88 women and 36 men) in treatment at Modum Psychiatric Center, Norway. The patient sample comprised a mixed psychiatric population of whom 39 were diagnosed with posttraumatic stress disorder (PTSD). Serum blood samples for cytokine analysis and measures of mental distress using Global Severity Index were collected at admission (T0), halfway (T1), and before discharge (T2). Other factors assessed were age, gender, and the use of antidepressants and anti-inflammatory drugs. Multilevel modeling was used for longitudinal analyses to assess the repeated cytokine samples within each patient.ResultsOverall level of IL-1RA was higher in PTSD patients when compared to those without PTSD (P=0.021). The level of IL-1β, MCP-1, and TNF-α increased over time in PTSD compared to non-PTSD patients (P=0.025, P=0.011 and P=0.008, respectively). All patients experienced reduced mental distress as measured by self-reported Global Severity Index scores. Stratified analysis showed that PTSD patients who used anti-inflammatory drugs had higher levels of IL-1β (P=0.007) and TNF-α (P=0.049) than PTSD patients who did not use such drugs.ConclusionThe study indicates that traumatized patients may have a distinct neuroimmune development during recovery. Their activated immune system shows even further activation during their rehabilitation despite symptom reduction.

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“…In recent years, evidence has shown that cytokines play an important role in mental health and the pathophysiology of mental disorders, including disorders which are highly comorbid with EDs such as depression (Dowlati et al, 2010;Lichtblau et al, 2013), anxiety disorders (Baldwin et al, 2017;Quagliato and Nardi, 2017), post-traumatic stress disorder (Hussein et al, 2017;Waheed et al, 2018), and sleep disorders (Weschenfelder et al, 2012). Cytokines have also been linked with body weight and its regulation (Fonseka et al, 2016); for example, plasma levels of pro-inflammatory cytokine IL-6 have been shown to correlate positively with body mass index (BMI) (Himmerich et al, 2006;Schmidt et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

A meta-analysis of cytokine concentrations in eating disorders

Dalton

Bartholdy

Robinson

et al. 2018

Journal of Psychiatric Research

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149

111

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Cytokines are signalling molecules, which play an important role in both immune system function and brain development and function, and subsequently mental states and behaviour. Cytokines have been implicated in eating disorders (EDs) due to their role in psychological health, body weight and appetite regulation. This meta-analysis examined cross-sectional and longitudinal studies measuring concentrations of cytokines in individuals with EDs. Using PRISMA guidelines, we systematically reviewed relevant articles in PubMed, Web of Science, and MEDLINE. Random-effects meta-analyses were conducted for interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β, and tumor necrosis factor (TNF)-α, independently, firstly with all EDs combined and then stratified by ED diagnosis. Twenty-five studies were included: serum/plasma cytokine concentrations were measured in people with anorexia nervosa (AN) in 23 studies and bulimia nervosa (BN) in 4 studies. TNF-α and IL-6 were elevated in ED participants compared to healthy controls (HCs). Specifically, this pattern was seen only when comparing AN participants to HCs. Concentrations of these cytokines did not differ between people with BN and HCs. IL-1β and TGF-β did not differ between HCs and any ED group. Therefore, AN seems to be associated with elevated concentrations of TNF-α and IL-6. Considering the role of cytokines in appetite, mood regulation, and anxiety, these pro-inflammatory cytokines could be a potential future drug target to help people with AN, not only with weight gain, but also with various coexisting psychological problems. Future studies should consider confounding factors that affect cytokine concentrations and report ED-relevant clinical characteristics.

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A SYSTEMATIC REVIEW OF TUMOR NECROSIS FACTOR-α IN POST-TRAUMATIC STRESS DISORDER: EVIDENCE FROM HUMAN AND ANIMAL STUDIES

Abstract: SUMMARY Background: Growing evidence suggests a pathophysiological role of cytokines in post-traumatic stress disorder (PTSD

Cited by 21 publications

References 30 publications

Mitochondria, Microglia, and the Immune System—How Are They Linked in Affective Disorders?

Mitochondria, Microglia, and the Immune System—How Are They Linked in Affective Disorders?

PTSD patients show increasing cytokine levels during treatment despite reduced psychological distress

A meta-analysis of cytokine concentrations in eating disorders

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