Different cytokine patterns associate with melancholia severity among inpatients with major depressive disorder

Abstract

Background Six melancholic features (MFs) of the Hamilton Depression Rating Scale (HAM-D6) represent the construct of melancholia along a continuum of severity (from least to most severe: depressed mood, work and activities, somatic symptoms, psychic anxiety, guilty feelings, psychomotor retardation). We aimed to evaluate the association between these MFs and inflammatory cytokines (IC) in the blood. Methods Each IC [interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2), IL-4, IL-6, IL-10, and IL-17] was associated with the HAM-D6 MFs of 139 severely depressed inpatients, using multiple linear regressions adjusted for covariates. Levels were compared with those of 100 healthy controls. Results Depressed mood was associated with higher levels of IL-4 ( β = 0.167; p = 0.041). Psychic anxiety: lower IL-17 levels ( β = –0.173; p = 0.039). Guilt feelings: lower IL-2 levels ( β = −0.168; p = 0.041) Psychomotor retardation: higher IL-6 levels ( β = 0.195; p = 0.017). Depressed patients’ TNF-α, INF-γ, and IL-4 levels were not significantly different from controls. Depressed patients’ IL-2, IL-6, IL-10, and IL-17 levels were higher than those of controls ( p <0.001). Conclusion Less severe MFs (depressed mood, psychic anxiety, and guilt feelings) were associated with an anti-inflammatory pattern (higher IL-4, lower IL-17 and lower IL-2, respectively). The presence of the most severe MF, psychomotor retardation, was associated with a higher pro-inflammatory response (higher IL-6).

Increased telomerase activity in major depressive disorder with melancholic features: Possible role of pro-inflammatory cytokines and the brain-derived neurotrophic factor

“…Besides, the inconsistent results may be due to different subtypes of MDD. For example, a higher IL-6 response was correlated with the presence of the most severe melancholic features ( Primo de Carvalho Alves & Sica da Rocha, 2020 ). It seems important to select a single subtype of MDD and measure cytokine levels in serum to reduce confounding factors.…”

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

“…Moreover, the prevalence of depression is higher among patients suffering from immune-mediated inflammatory disorders ( 10 ), and immunomodulation improves their depressive symptomatology irrespective of their effects on physical illness ( 11 ). Increased inflammatory markers have also been associated with specific subgroups of depressed patients, particularly those responding poorly to conventional antidepressants ( 12 , 13 ), and those with high levels of anxiety ( 14 ), sleep disturbance ( 15 ), anhedonia ( 16 ), and psychomotor retardation ( 17 , 18 ) — a cluster of symptoms that have been referred to as “depressive-inflammatory.” Therefore, targeting inflammation in depression may be a viable treatment strategy, and recent meta-analyses have described encouraging effects of anti-inflammatory agents as adjunctive treatments in depressed patients ( 19 ).…”

Indole-3-Carbinol Selectively Prevents Chronic Stress-Induced Depression-but not Anxiety-Like Behaviors via Suppressing Pro-Inflammatory Cytokine Production and Oxido-Nitrosative Stress in the Brain

“…For example, the over-activation of microglia has been repeatedly reported to mediate the progression of depression in rodent animals ( Zhao et al, 2016 ; Duan et al, 2020 ; Jing Li et al, 2020 ; Wu et al, 2020 ; Kumar et al, 2021 ), and suppression of neuroinflammation by minocycline treatment could can ameliorate depressive symptoms ( Wang et al, 2020 ; Bassett et al, 2021 ). Individuals suffering from depression have increased levels of pro-inflammatory cytokines in the blood ( Petralia et al, 2020 ; Primo de Carvalho Alves and Sica da Rocha, 2020 ). Administration of clinically-available antidepressants can down-regulate the levels of pro-inflammatory cytokines in the blood in depressed patients and in brain tissues in animals ( Du et al, 2016 ; Lu et al, 2019 ; Wang et al, 2019 ).…”

“…Increased neuroinflammatory response is a novel hypothesis for the explanation of the pathogenesis of psychologcial disorders ( Dantzer, 2006 ; Kubera et al, 2011 ; Ramirez et al, 2017 ; Weber et al, 2017 ; Dantzer, 2018 ; Chaves-Filho et al, 2019 ; Bekhbat et al, 2022 ). Researchers have observed high levels of pro-inflammatory cytokines including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in the blood of patients suffering from depression and anxiety ( Tang et al, 2018 ; Petralia et al, 2020 ; Primo de Carvalho Alves and Sica da Rocha, 2020 ). In rodent models of depression and anxiety, high levels of pro-inflammatory cytokines and low levels of anti-inflammatory mediators such as IL-10 and IL-4 in the brain are also correlated with the progression of abnormal behaviors ( Wang et al, 2018 ; Walker et al, 2019 ; Zhang et al, 2019 ; Guha et al, 2020 ; Wu et al, 2021 ).…”