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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Correlation of Specific Inflammatory Markers With the Occurrence of Depression in Patients With Psoriasis and Their Use as Biomarkers for the Diagnosis Of Depression
Μήτσιου, Ε., Kyriakou, A. E., Parlapani, E., Trigoni, A., Trakatelli, M. G., Apalla, Z., Sotiriadis, D., Lazaridou, E., & Patsatsi, A. (2024) · Dermatology Practical & Conceptual · doi:10.5826/dpc.1402a104 · Cited by 7
The communication between chikungunya infection and the central nervous system
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Association analysis between organophosphorus flame retardants exposure and the risk of depression: Data from NHANES 2017–2018
Chen, Y.-X., Zheng, J., & Zhang, X.-F. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.04.004 · Cited by 7
Identification of inflammatory markers suitable for non-invasive, repeated measurement studies in biobehavioral research: A feasibility study
Schenk, H., van Ockenburg, S. L., Nawijn, M. C., de Jonge, P., & Rosmalen, J. G. M. (2019) · PLoS ONE · doi:10.1371/journal.pone.0221993 · Cited by 7
Clenbuterol attenuates immune reaction to lipopolysaccharide and its relationship to anhedonia in adolescents
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Assessment of alcohol consumption in depression follow-up using self-reports and blood measures including inflammatory biomarkers
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Structural Modification of the Antidepressant Mianserin Suggests That Its Anti-inflammatory Activity May Be Independent of 5-Hydroxytryptamine Receptors
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“Patients with MDD have elevated levels of serum pro-inflammatory cytokines, which are restored to levels similar to healthy controls in patients that respond to treatment (3).”
Background
Interleukin-1 Beta in peripheral blood mononuclear cell lysates as a longitudinal biomarker of response to antidepressants: a pilot study
Ferentinos, P., Maratou, E., Antoniou, A., Serretti, A., Smyrnis, N., & Moutsatsou, P. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.801738 · Cited by 7
“On the other hand, other studies found no significant associations between plasma or serum concentrations of several cytokines (including IL1β) and depression severity scores (57, 58).”
Background
Interleukin-8 is a potential inflammation biomarker in major depressive disorder
Versel, J. L., Cantos, A., Castillo, M. F. R., Fatourou, E., Sinacore, J. M., & Halaris, A. E. (2024) · Journal of Affective Disorders Reports · doi:10.1016/j.jadr.2024.100828 · Cited by 6
The Antidepressant Mirtazapine Rapidly Shifts Hepatic B Cell Populations and Functional Cytokine Signatures in the Mouse
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Enlarged cross-sectional area of the left vagus nerve in patients with major depressive disorder
Schreiber, L. S., Wozniak, D., Scheller, E., Böttcher, E., Pelz, J. O., & Schmidt, F. M. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1237983 · Cited by 6
SuPAR in major depression: Association with 26 weeks antidepressant response and 10-year depression outcomes
Haupt, T. H., Elfving, B., Eugen‐Olsen, J., Mors, O. N., & Köhler‐Forsberg, O. (2023) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2023.100685 · Cited by 6
The Inflammatory Hypothesis of Depression: Implications for Diagnosis and Practice
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Is There an Association or Not?—Investigating the Association of Depressiveness, Physical Activity, Body Composition and Sleep With Mediators of Inflammation
Schmidt, F. M., Mergl, R., Minkwitz, J., Holdt, L. M., Teupser, D., Hegerl, U., Himmerich, H., & Sander, C. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00563 · Cited by 6
“Potentially, it needs a certain threshold or symptom load of depression, which our sample did not exhibit, that leads to an immune activation, as a dependency of the cytokine levels from the depression severity and state has been found (44).”
Background
Multimodal Psychotherapeutic Inpatient Therapy of Depression Is Successful in Patients With High Cytokine Production
Peters, E. M. J., Neusetzer, M., Akinci, S., Murat, A., Treuherz, S., Rose, M., Leweke, F., Leichsenring, F., Conrad, M. L., & Kruse, J. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.571636 · Cited by 6
The Role of Immune System in Depression Disorder
Hoseinzadeh, F., Abadi, P. H., Agheltar, M., Aghayinejad, A., Torabian, F., Rezayat, A. A., Akbarzadeh, F., & Rahimi, H. R. (2016) · Health · doi:10.4236/health.2016.815167 · Cited by 6
Expression levels of interferon-ɣ and type 2 deiodinase in patients diagnosed with recurrent depressive disorders
Gałecka, E., Talarowska, M. E., Maes, M. H. J., Su, K., Górski, P., Kumor‐Kisielewska, A., & Szemraj, J. (2017) · Pharmacological Reports · doi:10.1016/j.pharep.2017.08.009 · Cited by 6
Interleukin-10 promoter gene polymorphisms are associated with the first major depressive episode in chronic hepatitis C patients
da Cunha, L. R., Vieira, D. A., Giampietro, Y. G., Gomes, A. D., de Faria, C. L. L., de Melo, F. F., Teixeira, R., Teixeira‐Carvalho, A., de Oliveira, L. M., Martins‐Filho, O. A., et al. (2018) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2018.11.015 · Cited by 6
Inflammatory Cytokines as a Shared Pathophysiological Pathway in Depression and Chronic Insomnia: A Narrative Review of Mechanisms and Clinical Implications
Ren, N., Zhang, X., Yu, Z., Che, Y., Zhang, Y., Song, M., & Mao, H. (2026) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s585611 · Cited by 6
Cytokine associated with severity of depressive symptoms in female nurses in Korea
Kim, Y., Pang, Y., Park, H., Kim, O., & Lee, H. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1194519 · Cited by 6
“Regarding the severity of depression, some studies did not find a relationship between cytokines and disease severity (44, 45) or showed a negative correlation between serum cytokine levels and depression severity in patients with major depression (46), pregnant women with depressive symptoms (47), and patients with b…”
Background
Association of psychosis, affective disorders and diseases affecting the immune system
Larsen, J. B., Iversen, V. C., & Reitan, S. K. (2017) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2017.1402952 · Cited by 5
“Also genetic [2] and pharmacological data indicate a potential connection between immune system and psychiatry [3].”
BackgroundResult
Short-term oestrogen as a strategy to prevent postpartum depression in high-risk women: protocol for the double-blind, randomised, placebo-controlled MAMA clinical trial
Høgh, S., Hegaard, H. K., Renault, K. M., Cvetanovska, E., Kjærbye‐Thygesen, A., Juul, A., Borgsted, C., Bjertrup, A. J., Miskowiak, K. W., Væver, M. S., et al. (2021) · BMJ Open · doi:10.1136/bmjopen-2021-052922 · Cited by 5
Neuropsychiatric Outcomes and Sleep Dysfunction in COVID-19 Patients: Risk Factors and Mechanisms
Karkala, A., Tzinas, A., Kotoulas, S., Zacharias, A., Sourla, E., & Pataka, A. (2023) · NeuroImmunoModulation · doi:10.1159/000533722 · Cited by 5
“It has been proposed that such differences could be due to different immune system functions [111, 112] or to different hormone regulation [113], underlining the need of considering gender differences in order to promote more individualized care.”
Background
Anxiolytic Effect of Carvedilol in Chronic Unpredictable Stress Model
de Sousa, C. N. S., Medeiros, I. D. S., Vasconcelos, G. S., de Aquino, G. Â., Filho, F. M. S. C., de Almeida, J. C., Alves, A. P. N. N., Macêdo, D. S., Leal, L. K. A. M., & Vasconcelos, S. M. M. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/6906722 · Cited by 5
“Several studies have reported high circulating levels of IFN-γ in anxiety patients [89, 90].”
Prescription Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Depression among Adults with Inflammatory Chronic Conditions in the United States
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Dong, Z., Bi, B., Li, R., Wang, X., Liu, H., Wu, G., Sun, Z., Pu, E., He, C., Zhang, Y., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03738-0 · Cited by 4
Central hypocretin/orexin administration alleviates sleep/wake disturbances, anhedonia, and neuroinflammation in an animal model of seasonal affective disorder
Costello, A., Linning‐Duffy, K., Shi, J., Lonstein, J. S., & Yan, L. (2026) · Annals of Medicine · doi:10.1080/07853890.2025.2611202 · Cited by 4
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“Interestingly, previous studies have shown that IL-5 and IL-13 are positively correlated with depressive behavior, and IL-5 and IL-13 may be involved in the pathogenesis of depression (46,47).”
The relationship between plasma interleukin-6 and cognition based on curve correlation in drug-naïve patients with major depressive disorder
Wang, X., Xie, J., Yang, Y., Li, M., Li, G., Zhang, X., & Li, J. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.09.172 · Cited by 4
The effect of ketamine on microglia and proinflammatory cytokines in the hippocampus of depression-like rat
Chen, Q., Feng, J., Liu, L., Wang, X., Wan, Y., Mao, L., Wang, M.-H., & Zhang, C. (2017) · Neuropsychiatry · doi:10.4172/neuropsychiatry.1000183 · Cited by 4
“Several researches have shown that inflammatory processes were involved in the pathogenesis of major depression [19,20].”
Background
Measurement
Koenig, H. G., VanderWeele, T. J., & Peteet, J. R. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780190088859.003.0002 · Cited by 5
The Roles of T Cells in Clinical Depression
Toben, C. G., & Baune, B. T. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811073-7.00007-6 · Cited by 4
The Biological Underpinnings of Mood Disorders Interact With Early Trauma, Sexual Abuse and Neuroticism: Implications for Psychiatric Classification and Treatment
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A Local Community Course That Raises Mental Wellbeing and Pro-Sociality
Krekel, C., Jan-emmanuel De Neve, A., Fancourt, D. E., & Layard, R. (2020) · London School of Economics and Political Science Research Online (London School of Economics and Political Science) · Cited by 4
Depression But Not Inflammatory Markers Are Increased in Family Versus Nonfamily Caregivers of Persons With Dementia
Sadowska, A., Wyczałkowska-Tomasik, A., Zegarow, P., & Czarkowska‐Pączek, B. (2020) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988720901782 · Cited by 4
Understanding the Religion, Mental, and Social Health Relationship
Koenig, H. G., VanderWeele, T. J., & Peteet, J. R. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780190088859.003.0016 · Cited by 7
Epidemiology and risk of psychiatric disorders in patients with polymyositis and dermatomyositis: a nationwide population-based cohort study in Taiwan
Lee, I.-P., Lee, Y., Wu, F., Su, C., Kao, J., Lin, S.-H., & Chang, Y. (2025) · BMJ Open · doi:10.1136/bmjopen-2024-097829 · Cited by 3
“17 Similar results were reported in a case of dermatomyositis where, during the course of the disease, elevated inflammatory markers were correlated with worsening depression.”
Dysregulated miR-1246 and miR-1253 link inflammatory protein markers in plasma to major depressive disorder in female adolescents
Johannessen, K., Braný, D., Dvorská, D., Krivošová, M., Oppa, M., Ondrejka, I., Strnádel, J., Ferencová, N., Tonhajzerová, I., Daňková, Z., et al. (2025) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2025.101108 · Cited by 3
“In this study, only PDGF-BB and IL-7 were significantly elevated in treatment-naïve female adolescents with MDD compared to healthy controls, consistent with findings in plasma from adult patients with MDD (Annam et al., 2024; Dahl et al., 2014).”
Efficacy of Anti-Inflammatory Treatment in Depression
Köhler‐Forsberg, O., & Benros, M. E. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811073-7.00030-1 · Cited by 3
Combined repetitive transcranial magnetic stimulation and medication treatment for depression is associated with serum amyloid a level: Evidence from naturalistic clinical practice
Xu, Y., Li, H., Wei, Y., Mao, H., & Yu, Z. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1002816 · Cited by 3
“Nevertheless, whether SAA is a state marker or a trait marker is still unclear due to the configuration results (Kling et al., 2007; Dahl et al., 2014).”
Background
The BrainDrugs-epilepsy study: A prospective open-label cohort precision medicine study in epilepsy
Marstrand-Joergensen, M. R., Dam, V. H., Vinter, K., Ip, C.-T., Jensen, K. H. R., Jørgensen, M. B., Hoei‐Hansen, C. E., Ozenne, B., Fisher, P. M., Knudsen, G. M., et al. (2023) · Neuroscience Applied · doi:10.1016/j.nsa.2023.101136 · Cited by 4
“…and complement system) (Vezzani et al., 2011; Zhang et al., 2014; Kanemoto et al., 2000, 2003; Salzmann et al., 2008; Jamali et al., 2010; Pollard et al., 2012; Dahl et al., 2014; Howren et al., 2009; Dowlati et al., 2010; Liu et al., 2012) and for blood purine concentrations (Beamer et al., 2021).”
Bupropion Associated Immunomodulatory Effects on Peripheral Cytokines in Male with Major Depressive Disorder
Huang, C.-C., Chu, H., Lin, Y., Tsai, C., Liang, C., & Yeh, T. (2023) · Journal of Medical Sciences · doi:10.4103/jmedsci.jmedsci_124_23 · Cited by 3
Can gut flora changes be new biomarkers for depression?
Lin, P., & Li, Q. (2017) · Frontiers in Laboratory Medicine · doi:10.1016/j.flm.2017.08.002 · Cited by 3

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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