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The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery
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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“High levels of inflammation are associated with many mental health conditions including depression [29–30].”
From Singing modulates mood, stress, cortisol, cytokine and neuropeptide activity in cancer patients and carers (2016) · cites this paper as [29]
In the citing paper
“Following research showing that both acute and chronic stress and depression are associated with increases in stress hormones and inflammatory immune response [29–30]”
From Singing modulates mood, stress, cortisol, cytokine and neuropeptide activity in cancer patients and carers (2016) · cites this paper as [29]
In the citing paper
“Increased levels of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α (TNF-α) and interferon-γ (IFNγ) have been consistently reported in the blood of depressed patients [138,139,140]”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [140]
In the citing paper
“Moreover, antidepressant treatment seem to attenuate this immunological response [140,143].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [140]
In the citing paper
“Interestingly, treatment with antidepressants can result in an antiinflammatory response throughout the brain, mitigating the inflammatory unbalance to homeostatic levels and normalizing BDNF concentrations [83, 84].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [83]
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Bhardwaj, S., Kaur, R., Kumari, P., Sharma, S. K., Pasricha, C., Jamwal, N., Singh, R., Arora, P., Kaur, P., & Sahu, S. K. (2024) · BIO Web of Conferences · doi:10.1051/bioconf/20248601039
“As well as being found to have elevated plasma levels of IL-1b, IL-1 receptor antagonist, IL-5, IL-6, IL-7, IL-8, IL-10, granulocyte colony-stimulating factor (G-CSF), and IFN-c [71].”
BackgroundDahl, J., Ormstad, H., Aass, H. C. D., Malt, U. F., & Andreassen, O. A. (2024) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2023.2290654
“Previously we have found that a broader range of cytokines were elevated in a depressive episode and, normalized after recovery [22].”
BackgroundInfluentialSelf-citationKayser, J. M., Petry, F., Souza, M. A., Schindler, M. S. Z., Morgan, L. V., Rodrigues, G. Z. P., Mazon, S. C., Aguiar, G. P. S., Pitta, M. G. D. R., Pitta, I. D. R., et al. (2024) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000785 · Cited by 1
“Several studies have reported high levels of proinflammatory cytokines in blood and cerebrospinal fluid (CSF) of patients with MDD, and this was positively correlated with clinical severity of the illness (Martinez et al ., 2012; Dahl et al ., 2014; Wang and Miller, 2018; Zou et al ., 2018).”
Cytokines, Chemokines, and Inflammatory Indicators in Bipolar Disorder
Poletti, S., Dallaspezia, S., & Spadini, S. (2024) · Springer eBooks · doi:10.1007/978-3-031-32035-4_22-1
Depression in Parkinson’s Disease: A Trajectory Linking Gut Microbiota and Neuroinflammation
Kujur, P. P., Sahu, M. R., & Mondal, A. C. (2024) · Integrated science · doi:10.1007/978-3-031-72079-6_13
Measures of Psychiatric Changes in Type 1 Diabetes: Depression, Bipolar, and Beyond
CYRANKA, K. M. (2024) · Springer eBooks · doi:10.1007/978-3-031-32046-0_33-1
Metadata
- 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
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 45
- Pages
- 77-86
- ISSN
- 0306-4530 (ISSN-L)
- 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
- 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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