Targeting the Inflammatory Pathway as a Therapeutic Tool for Major Depression

Noto, Cristiano; Rizzo, Lucas B.; Mansur, Rodrigo B.; McIntyre, Roger S.; Maes, Michaël; Brietzke, Elisa

doi:10.1159/000356549

Cited by 38 publications

(20 citation statements)

References 92 publications

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“…Alterations in serum levels of cytokines have been demonstrated in several psychiatric disorders in adults (11,12,14,30). In pediatric population, TBARS, thiobarbituric acid reactive substances; BDNF, brain-derived neurotrophic factor; IL-2, interleukin-2; IL-4, interleukin-4; IL-6, interleukin-6; IL-10, interleukin-10; IL-17A, interleukin-17A; IFN-c, interferon-gamma; TNF-a, tumor necrosis factor-a; CCL11, chemokine (C-C Motif) ligand 11; IP-10, IFN-c inducible protein 10; MCP-1, monocyte chemoatractant protein 1; sTNFR1, soluble TNF-a receptor 1; sTNFR2, soluble TNF-a receptor 2. the data available are less substantial.…”

Section: Discussionmentioning

confidence: 99%

“…Neurotrophic proteins, immune-inflammatory axis, and oxidative stress pathways have been reported to impact brain structure and function in a time and context-dependent manner and are relevant to neurodevelopment in physiological conditions (8,9). Several studies have reported abnormalities in neurotrophic factors, such as the brain-derived neurotrophic factor (BDNF), inflammatory mediators such as cytokines and in oxidative stress balance with increases in oxidative markers such as thiobarbituric acid-reactive substances (TBARS) in adult psychiatric disorders, including mood disorders, addictions, and schizophrenia (10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inflammation, neurotrophism and oxidative stress and childhood psychopathology in a large community sample

Cunha

Asevedo

Mansur

et al. 2015

Acta Psychiatr Scand

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inflammation, neurotrophism and oxidative stress and childhood psychopathology in a large community sample

Cunha

Asevedo

Mansur

et al. 2015

Acta Psychiatr Scand

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“…In depression, proinflammatory cytokines were found to interact with the HPA axis, to stimulate the serotonin-depleting indolamine-2,3-dioxygenase and to trigger serotonin reuptake [6,8,9]. Levels of proinflammatory cytokines were repeatedly found to be elevated in depressed patients as well as in animal models of depression [6,10,11], potentially representing an inflammation-associated specific subtype of MDD [12,13,14] and a target for new antidepressant treatment strategies [15,16]. …”

Section: Introductionmentioning

confidence: 99%

Impact of Serum Cytokine Levels on EEG-Measured Arousal Regulation in Patients with Major Depressive Disorder and Healthy Controls

et al. 2016

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Background: In major depressive disorder (MDD), findings include hyperstable regulation of brain arousal measured by electroencephalography (EEG) vigilance analysis and alterations in serum levels of cytokines. It is also known that cytokines affect sleep-wake regulation. This study investigated the relationship between cytokines and EEG vigilance in participants with MDD and nondepressed controls, and the influence of cytokines on differences in vigilance between the two groups. Methods: In 60 patients with MDD and 129 controls, 15-min resting-state EEG recordings were performed and vigilance was automatically assessed with the VIGALL 2.0 (Vigilance Algorithm Leipzig). Serum levels of the wakefulness-promoting cytokines interleukin (IL)-4, IL-10, IL-13 and somnogenic cytokines tumor necrosis factor-α, interferon-γ and IL-2 were measured prior to the EEG. Results: Summed wakefulness-promoting cytokines, but not somnogenic cytokines, were significantly associated with the time course of EEG vigilance in the MDD group only. In both groups, IL-13 was significantly associated with the course of EEG vigilance. In MDD compared to controls, a hyperstable EEG vigilance regulation was found, significant for group and group × time course interaction. After controlling for wakefulness-promoting cytokines, differences in vigilance regulation between groups remained significant. Conclusions: The present study demonstrated a relationship between wakefulness-promoting cytokines and objectively measured EEG vigilance as an indicator for brain arousal. Altered brain arousal regulation in MDD gives support for future evaluation of vigilance measures as a biomarker in MDD. Since interactions between cytokines and EEG vigilance only moderately differed between the groups and cytokine levels could not explain the group differences in EEG vigilance regulation, cytokines and brain arousal regulation are likely to be associated with MDD in independent ways.

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“…Changes in proinflammatory and cell‐mediated immune cytokines have been thoroughly documented in psychiatric diseases such as major depressive disorder (MDD). In fact, in addition to genetic and environmental factors, a robust association has been defined for MDD, immune response, and inflammation . Evidence suggests that antidepressants, such as the tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), may function to normalize cytokine levels, and this may be an additional therapeutic mechanism secondary to their effect on neurotransmitters .…”

Section: Microbiome Inflammation and Moodmentioning

confidence: 99%

The Microbiome in Mental Health: Potential Contribution of Gut Microbiota in Disease and Pharmacotherapy Management

Flowers

Ellingrod

2015

Pharmacotherapy

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The gut microbiome is composed of ~10(13) -10(14) microbial cells and viruses that exist in a symbiotic bidirectional communicative relationship with the host. Bacterial functions in the gut have an important role in healthy host metabolic function, and dysbiosis can contribute to the pathology of many medical conditions. Alterations in the relationship between gut microbiota and host have gained some attention in mental health because new evidence supports the association of gut bacteria to cognitive and emotional processes. Of interest, illnesses such as major depressive disorder are disproportionately prevalent in patients with gastrointestinal illnesses such as inflammatory bowel disease, which pathologically has been strongly linked to microbiome function. Not only is the microbiome associated with the disease itself, but it may also influence the effectiveness or adverse effects associated with pharmacologic agents used to treat these disorders. This field of study may also provide new insights on how dietary agents may help manage mental illness both directly as well as though their influence on the therapeutic and adverse effects of psychotropic agents.

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Targeting the Inflammatory Pathway as a Therapeutic Tool for Major Depression

Cited by 38 publications

References 92 publications

Inflammation, neurotrophism and oxidative stress and childhood psychopathology in a large community sample

Inflammation, neurotrophism and oxidative stress and childhood psychopathology in a large community sample

Impact of Serum Cytokine Levels on EEG-Measured Arousal Regulation in Patients with Major Depressive Disorder and Healthy Controls

The Microbiome in Mental Health: Potential Contribution of Gut Microbiota in Disease and Pharmacotherapy Management

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