Cited by 425Tryptophan and brain disordersTreatment of Major DepressionStress Responses and Cortisol

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The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery

Dahl, Johan, Ormstad, Heidi, Aass, Hans Christian D., Malt, Ulrik Fredrik, Bendz, Lil Träskman, Sandvik, Leiv, Brundin, Lena, Andreassen, Ole A.·2014·Psychoneuroendocrinology

DOI 10.1016/j.psyneuen.2014.03.019

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Abstract

Background Cytokines are implicated in the pathophysiology of major depressive disorder (MDD). However, the pattern of alterations in cytokine levels is still unclear. The current study investigated the plasma levels of a range of cytokines in a follow-up design, with the aim of determining their involvement in depression.Methods Fifty medication-free MDD patients with a depressive episode and 34 healthy controls were included at baseline; the patients were followed up after 12 weeks. Before initiating treatment, the patients were diagnosed and assessed for depressive symptoms and blood for cytokine analysis was obtained. The same clinical assessments and cytokine measurements were performed after 12 weeks of "treatment as usual."Results The cytokines interleukin (IL)-1β, IL-1 receptor antagonist (IL-1Ra), IL-5, IL-6, IL-7, IL-8, IL-10, granulocyte colony-stimulating factor (G-CSF), and interferon gamma (IFNγ) were significantly elevated (p=0.01-0.047) in depressed patients at baseline compared to healthy controls. After 12 weeks of treatment, the plasma levels of seven of these nine cytokines (IL-1Ra, IL-6, IL-7, IL-8, IL-10, G-CSF, and IFNγ had decreased significantly compared to baseline and did not differ from those in the healthy controls. The depressive symptoms were simultaneously significantly reduced. In addition, the reduction to normal cytokines levels occurred only in those who met the recovery criteria.Conclusion A more general pattern of elevated cytokine levels is described herein relative to what has been described previously shown in MDD. Furthermore, recovery from depression was associated with reduction to normal levels of the majority of the measured cytokines. These results strongly support the notion that a complex network of cytokines is involved in the pathophysiology of MDD.

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“An increasing amount of clinical evidence has shown the presence of augmented levels of proinflammatory markers in the periphery and in the CNS (Maes et al., 1993; Rotter et al., 2013; Dahl et al., 2014).”
Background
Morinda officinalis oligosaccharides alleviate depressive‐like behaviors in post‐stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation
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“…cytokines were recorded before and after a 12-week antidepressant therapy in 50 depressed patients, a significant reduction in IL-6, IL-7, IL-8, IL-10, G-CSF, IFN-y and IL-1 receptor antagonist was observed—but only in patients who responded to the antidepressant treatment (Dahl et al., 2014).”
Background
Pro- and anti-inflammatory cytokines, but not CRP, are inversely correlated with severity and symptoms of major depression
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Influential
Inflammatory cytokines in major depressive disorder: A case–control study
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Influential
Changes in interleukin‐6 levels during electroconvulsive therapy may reflect the therapeutic response in major depression
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“In addition, several cytokines that were significantly elevated in patients with depression (including IL-1Ra, IL-6, IL-7, IL-8, IL-10, G-CSF and IFN-c) decreased to levels comparable to those of the healthy controls after 12 weeks of medical therapy among patients who met the recovery criteria (13).”
BackgroundResult
Effects of Antidepressant Treatment on Peripheral Biomarkers in Patients with Major Depressive Disorder (MDD)
Mosiołek, A., Pięta, A., Jakima, S., Zborowska, N., Mosiołek, J., & Szulc, A. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10081706 · Cited by 72
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BackgroundMethod
Differences in immunomodulatory properties between venlafaxine and paroxetine in patients with major depressive disorder
Chen, C., Yeh, Y., Kuo, S.-C., Liang, C., Ho, P., Huang, C., Yen, C.-H., Shyu, J., Lu, R., & Huang, S. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.10.009 · Cited by 72
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Interleukin-1 β-Targeted Treatment Strategies in Inflammatory Depression: Toward Personalized Care
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Inflammation and Immune Regulation as Potential Drug Targets in Antidepressant Treatment
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“Results of a variety of trials reporting on cytokines in depression [8, 43] allow the conclusion of increased concentrations of cytokines in patients suffering from major depression [6, 7], which supports the existence of an inflammatory cytokine-associated depressive sub-type [12].”
BackgroundResultInfluential
Chrysin promotes attenuation of depressive-like behavior and hippocampal dysfunction resulting from olfactory bulbectomy in mice
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Anti-inflammatory properties of commonly used psychiatric drugs
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Altered serum interleukin-7 and interleukin-10 are associated with drug-free major depressive disorder
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The Anti-Depressive Effects of Hesperidin and the Relative Mechanisms Based on the NLRP3 Inflammatory Signaling Pathway
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The inflammatory underpinning of depression: An historical perspective
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“Furthermore, the successful antidepressant response was also marked by a decrease in other inflammatory cytokines, such as IL-7, IL-8, G-CSF, IFN γ , IL-1Ra, and IL-10, which were only reduced in responders (Dahl et al., 2014).”
The protective effects of activating Sirt1/NF-κB pathway for neurological disorders
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Linking atypical depression and insulin resistance-related disorders via low-grade chronic inflammation: Integrating the phenotypic, molecular and neuroanatomical dimensions
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“decrease of pro-inflammatory cytokine blood levels especially after SSRI treatment (292,293,295,297,298).”
Background
Neurochemical factors associated with the antidepressant-like effect of flavonoid chrysin in chronically stressed mice
Filho, C. B., Jessé, C. R., Donato, F., Fabbro, L. D., de Gomes, M. G., Goes, A. T. R., Souza, L. C., Giacomeli, R., Antunes, M. S., Luchese, C., et al. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.09.005 · Cited by 67
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“Meta-analyses have gathered large evidence, particularly with C-reactive protein (CRP) [25, 26], interleukin-6 (IL-6) [23–27], tumour necrosis factor-α (TNF- α) [23, 24, 27] and IL-1 receptor antagonist (IL-1ra) [24–26] being elevated among patients with depression.”
Method
Curcumin Protects Against Chronic Stress-induced Dysregulation of Neuroplasticity and Depression-like Behaviors via Suppressing IL-1β Pathway in Rats
Fan, C., Song, Q., Wang, P., Li, Y., Yang, M., Liu, B., & Yu, S. Y. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.09.028 · Cited by 65
Predicting Treatment Outcome in Major Depressive Disorder Using Serotonin 4 Receptor PET Brain Imaging, Functional MRI, Cognitive-, EEG-Based, and Peripheral Biomarkers: A NeuroPharm Open Label Clinical Trial Protocol
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Interleukin‐6 and interleukin‐17 are related to depression in patients with rheumatoid arthritis
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Targeting Oxidative Stress, Cytokines and Serotonin Interactions Via Indoleamine 2, 3 Dioxygenase by Coenzyme Q10: Role in Suppressing Depressive Like Behavior in Rats
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Complement Has Brains—Do Intracellular Complement and Immunometabolism Cooperate in Tissue Homeostasis and Behavior?
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Ganoderma lucidum polysaccharides ameliorated depression-like behaviors in the chronic social defeat stress depression model via modulation of Dectin-1 and the innate immune system
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Telomere Shortening and Psychiatric Disorders: A Systematic Review
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Inflammatory Profiles in Depressed Adolescents Treated with Fluoxetine: An 8-Week Follow-up Open Study
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“, who reported higher levels of IL-1Ra in MDD patients; however, they also observed that treatment with SSRIs can reduce IL-1Ra levels [73].”
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Understanding the role of P2X7 in affective disorders—are glial cells the major players?
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“, 2009) and depression (Hiles et al., 2012; Liu et al., 2012; Dahl et al., 2014).”
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Effects of Religious vs. Conventional Cognitive-Behavioral Therapy on Inflammatory Markers and Stress Hormones in Major Depression and Chronic Medical Illness: A Randomized Clinical Trial
Berk, L., Bellinger, D. L., Koenig, H. G., Daher, N. S., Pearce, M., Robins, C. J., Nelson, B., Shaw, S. F., Cohen, H. J., & King, M. (2015) · Open Journal of Psychiatry · doi:10.4236/ojpsych.2015.53028 · Cited by 63
Recovery from major depressive disorder episode after non‐pharmacological treatment is associated with normalized cytokine levels
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Depressive symptoms in obesity: Relative contribution of low-grade inflammation and metabolic health
Delgado, I., Huet, L., Dexpert, S., Beau, C., Forestier, D., Ledaguenel, P., Aubert, A., Sauvant, J., Aouizerate, B., Magne, E., et al. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.02.030 · Cited by 60
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“81 Elevated levels of IL6 have been associated with suicidal ideation in at least eight studies(82) and IL-1beta, the IL-1 receptor antagonist (IL-1Ra), IL-5, IL-6, IL-7, IL-8, IL-10, granulocyte colony-stimulating factor and interferon gamma plasma levels have all been found to be elevated during depression.(83)”
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The longitudinal relationship between changes in wellbeing and inflammatory markers: Are associations independent of depression?
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Group Drumming Modulates Cytokine Response in Mental Health Services Users: A Preliminary Study
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Danzhi Xiaoyao San ameliorates depressive-like behavior by shifting toward serotonin via the downregulation of hippocampal indoleamine 2,3-dioxygenase
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Authors: Dahl, J., Ormstad, H., Aass, H. C. D., Malt, U. F., Bendz, L. T., Sandvik, L., Brundin, L., & Andreassen, O. A.
Affiliations: Vestre Viken Hospital Trust (NO)
Buskerud University College (NO)
Oslo University Hospital (NO)
Van Andel Institute (US)
Corresponding author: Dahl, Johan
ORCID: Ormstad, Heidi
Aass, Hans Christian D.
Malt, Ulrik Fredrik
Sandvik, Leiv
Brundin, Lena
Andreassen, Ole A.
Venue: Psychoneuroendocrinology
Publisher: Elsevier BV
Published: 2014-07
Volume: 45
Pages: 77-86
ISSN: 0306-4530 (ISSN-L)
DOI: 10.1016/j.psyneuen.2014.03.019
OpenAlex: W2134586420
Cited by: 424
References: 53
Citations by year: 2026: 15 · 2025: 22 · 2024: 30 · 2023: 75 · 2022: 35 · 2021: 50 · 2020: 36 · 2019: 37 · 2018: 30 · 2017: 34 · 2016: 33 · 2015: 19 · 2014: 7
FWCI: 9.49
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Psychoneuroendocrinology (publishedVersion)
PubMed (publishedVersion)
Lund University Publications (Lund University) (submittedVersion)
Funders: Helse Sør-Øst RHF
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: major depressive disorder, cytokines, plasma cytokines, interleukin-6, IL-10, interleukin-1 receptor antagonist, interferon-gamma, granulocyte colony-stimulating factor, recovery from depression, usual care
MeSH terms: Adult, Antidepressive Agents, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Severity of Illness Index, Up-Regulation, Case-Control Studies, Cytokines, Treatment Outcome, Inflammation Mediators, Recovery of Function

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The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery

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