Targeting inflammation: a potential approach for the treatment of depression

Bhatt, Shvetank; Devadoss, Thangaraj; Jha, Niraj Kumar; Baidya, Moushumi; Gupta, Gaurav; Chellappan, Dinesh Kumar; Singh, Sachin Kumar; Dua, Kamal

doi:10.1007/s11011-022-01095-1

Cited by 29 publications

(20 citation statements)

References 127 publications

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“…A causative role of cytokines in MDD is supported by a recent study that showed that administration of cytokines can cause depression-like behaviors and symptoms (Bhatt et al 2022) and from evidence that inflammation-based treatments and inflammation illnesses are linked to depressed mood or depressive disorders (Dantzer et al 2008, Capuron et al 2009Bhatt et al 2022). Further, blockade of cytokine signalling is associated with mood-enhancing effects (Tyring et al 2006;Hersey et al 2021) and most cytokines decrease with effective anti-depressant treatment (Dahl et al 2014;Bhatt et al 2022). The potential mechanism underlying these effects may be due to the role of pro-inflammatory cytokines in serotonin availability.…”

Section: Introductionmentioning

confidence: 97%

“…Cytokines can cross the blood brain barrier and affect central neural function, and increasing evidence suggests that abnormal inflammatory responses may play a role in the pathophysiology of MDD (Beurel et al 2020). A causative role of cytokines in MDD is supported by a recent study that showed that administration of cytokines can cause depression-like behaviors and symptoms (Bhatt et al 2022) and from evidence that inflammation-based treatments and inflammation illnesses are linked to depressed mood or depressive disorders (Dantzer et al 2008, Capuron et al 2009Bhatt et al 2022). Further, blockade of cytokine signalling is associated with mood-enhancing effects (Tyring et al 2006;Hersey et al 2021) and most cytokines decrease with effective anti-depressant treatment (Dahl et al 2014;Bhatt et al 2022).…”

Section: Introductionmentioning

confidence: 99%

“…Major depressive disorder (MDD) is a debilitating mental disorder, and a leading cause of disability globally (GBD, 2017). Individuals with MDD have a higher incidence of inflammatory illnesses such as diabetes, obesity and heart disease (Maes et al 2011; Buckley and Abbate, 2018) and higher levels of several proinflammatory cytokines (Beurel et al 2020;Osimo et al 2020;Bhatt et al 2022) than those without MDD. Accordingly, pro-inflammatory cytokines may contribute to the increased risk for those with MDD of cardiometabolic disease (CMD) (Celano et al 2011).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pro-inflammatory cytokines IL-1α, IL-6 and TNF-α in major depressive disorder: Sex-specific associations with psychological symptoms

Elgellaie

Thomas

Kaelle

et al. 2022

Preprint

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The pro-inflammatory cytokines IL-1α, IL-6 and TNF-α are associated with major depressive disorder, psychological distress, cardiovascular health, and obesity. However, there is limited research that has examined multiple associations between these variables, among individuals with major depressive disorder in comparison to a control cohort, including sex differences. In this study, data was analysed from 60 individuals with major depressive disorder and 60 controls, including plasma IL-1α, IL-6 and TNF-α, adiposity measures (body mass index; waist circumference), cardiovascular health indices (blood pressure; heart rate) and psychological symptoms (depressive severity; anxiety; hostility; stress). The cytokines were compared by group and sex, and correlated with measures of adiposity, cardiovascular health indices and psychological health. Plasma IL-1α and IL-6 were higher in major depressive disorder group versus control, but with a sex interaction for IL-6, with this group difference only among females. TNF-α did not differ between groups. IL-1α and IL-6 correlated with depressive severity, anxiety, hostility, and stress, while TNF-α correlated only with anxiety and hostility. Psychopathology was associated with IL-1α in males only, and with IL-6 and TNF-α in females only. None of the cytokines correlated with body mass index, waist circumference, blood pressure or heart rate. The result of group by sex interaction for IL-6, and sex specific associations between pro-inflammatory cytokines and psychometrics could be aetiologically important in depression interventions and treatments for females versus males, warranting further investigation.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pro-inflammatory cytokines IL-1α, IL-6 and TNF-α in major depressive disorder: Sex-specific associations with psychological symptoms

Elgellaie

Thomas

Kaelle

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Cytokines can cross the blood brain barrier and affect central neural function, and increasing evidence suggests that abnormal inflammatory responses may play a role in the pathophysiology of MDD (Beurel et al, 2020). A causative role of cytokines in MDD is supported by a recent study that showed that administration of cytokines can cause depression-like behaviors and symptoms (Bhatt et al, 2023) and from evidence that inflammation-based treatments and inflammation illnesses are linked to depressed mood or depressive disorders (Bhatt et al, 2023;Capuron et al, 2009;Dantzer et al, 2008). Further, blockade of cytokine signalling is associated with mood-enhancing effects (Hersey et al, 2022;Tyring et al, 2006) and most cytokines decrease with effective anti-depressant treatment (Bhatt et al, 2023;Dahl et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Pro‐inflammatory cytokines IL‐1α, IL‐6 and TNF‐α in major depressive disorder: Sex‐specific associations with psychological symptoms

Elgellaie

Thomas

Kaelle

et al. 2023

Eur J of Neuroscience

View full text Add to dashboard Cite

The pro‐inflammatory cytokines IL‐1α, IL‐6 and TNF‐α are associated with major depressive disorder, psychological distress, cardiovascular health and obesity. However, there is limited research that has examined multiple associations between these variables, particularly among individuals with major depressive disorder who are treatment free, in comparison with a control cohort, and including analyses of sex differences. In this study, data were analysed from 60 individuals with major depressive disorder and 60 controls, including plasma IL‐1α, IL‐6 and TNF‐α, adiposity measures (body mass index, waist circumference), cardiovascular health indices (blood pressure, heart rate) and psychological symptoms (depressive severity, anxiety, hostility, stress). The cytokines were compared by group and sex and correlated with measures of adiposity, cardiovascular health indices and psychological health. Plasma IL‐1α and IL‐6 were higher in major depressive disorder group versus control, but with a sex interaction for IL‐6, with this group difference only among females. TNF‐α did not differ between groups. IL‐1α and IL‐6 correlated with depressive severity, anxiety, hostility and stress, whereas TNF‐α correlated only with anxiety and hostility. Psychopathology was associated with IL‐1α in males only and with IL‐6 and TNF‐α in females only. None of the cytokines correlated with body mass index, waist circumference, blood pressure or heart rate. The result of group by sex interaction for IL‐6 and sex‐specific associations between pro‐inflammatory cytokines and psychometrics could be aetiologically important in depression interventions and treatments for females versus males, warranting further investigation.

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“…Mounting evidence continues to implicate neuroinflammation in the pathogenesis of neurodegenerative diseases [ 1 ], as well as neurological disorders such as depression [ 2 ] and epilepsy [ 3 ]. Neuroinflammation has also contributed to neurocognitive deficits of parasitic infections such as cerebral malaria [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection by Skimmianine in Lipopolysaccharide-Activated BV-2 Microglia

et al. 2023

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Skimmianine is a furoquinoline alkaloid which is found in the Zanthoxylum genus and also in other plants of the Rutaceae family. This study evaluated the effects of skimmianine on the production of pro-inflammatory mediators in LPS-activated BV-2 microglia. Cultured BV-2 cells were treated with skimmianine (10, 20 and 30 μM), followed by stimulation with LPS (100 ng/mL). Levels of TNFα and IL-6 in cell supernatants were measured using ELISA, while NO and PGE2 levels were evaluated with Griess assay and EIA, respectively. Western blotting was used to determine the protein expression of iNOS, COX-2, phospho-p65 and phospho-IκBα. Results showed that Skimmianine reduced LPS-induced elevated the secretion of TNFα, IL-6, NO, and PGE2, as well as the increased protein expression of iNOS and COX-2. Experiments to elucidate the mechanisms of the anti-neuroinflammatory activity of skimmianine revealed the significant inhibition of LPS-induced increased NF-κB-mediated luciferase activity. Pre-treatment with skimmianine also reduced LPS-induced the increased phosphorylation of NF-κB/p65 and IκBα proteins. Furthermore, skimmianine interfered with the binding capacity of NF-κB to consensus sites. Skimmianine pre-treatment protected HT-22 cells from toxicity induced by microglia-conditioned media, as well as increasing MAP-2 expression. The results of this study suggest that skimmianine inhibits neuroinflammation in LPS-activated microglia by targeting the NF-κB activation pathway. Skimmianine also produced neuroprotection against neurotoxicity induced by microglia-conditioned media.

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Targeting inflammation: a potential approach for the treatment of depression

Cited by 29 publications

References 127 publications

Pro-inflammatory cytokines IL-1α, IL-6 and TNF-α in major depressive disorder: Sex-specific associations with psychological symptoms

Pro-inflammatory cytokines IL-1α, IL-6 and TNF-α in major depressive disorder: Sex-specific associations with psychological symptoms

Pro‐inflammatory cytokines IL‐1α, IL‐6 and TNF‐α in major depressive disorder: Sex‐specific associations with psychological symptoms

Neuroprotection by Skimmianine in Lipopolysaccharide-Activated BV-2 Microglia

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