Cited by 844Tryptophan and brain disordersStress Responses and CortisolTreatment of Major Depression

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Inflammation: Depression Fans the Flames and Feasts on the Heat

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Kiecolt-Glaser, Janice K., Derry, Heather M., Fagundes, Christopher P.·2015·American Journal of Psychiatry

DOI 10.1176/appi.ajp.2015.15020152PMC PMC6511978

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Abstract

Depression and inflammation fuel one another. Inflammation plays a key role in depression's pathogenesis for a subset of depressed individuals; depression also primes larger cytokine responses to stressors and pathogens that do not appear to habituate. Accordingly, treatment decisions may be informed by attention to questions of how (pathways) and for whom (predispositions) these links exist, which are the focus of this article. When combined with predisposing factors (moderators such as childhood adversity and obesity), stressors and pathogens can lead to exaggerated or prolonged inflammatory responses. The resulting sickness behaviors (e.g., pain, disturbed sleep), depressive symptoms, and negative health behaviors (e.g., poor diet, a sedentary lifestyle) may act as mediating pathways that lead to further, unrestrained inflammation and depression. Depression, childhood adversity, stressors, and diet can all influence the gut microbiome and promote intestinal permeability, another pathway to enhanced inflammatory responses. Larger, more frequent, or more prolonged inflammatory responses could have negative mental and physical health consequences. In clinical practice, inflammation provides a guide to potential targets for symptom management by signaling responsiveness to certain therapeutic strategies. For example, a theme across research with cytokine antagonists, omega-3 fatty acids, celecoxib, and exercise is that anti-inflammatory interventions have a substantially greater impact on mood in individuals with heightened inflammation. Thus, when inflammation and depression co-occur, treating them in tandem may enhance recovery and reduce the risk of recurrence. The bidirectional links between depression, inflammation, and disease suggest that effective depression treatments could have a far-reaching impact on mood, inflammation, and health.

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Interleukin-6, C-reactive protein and biochemical parameters during prolonged intermittent fasting.
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Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-α and ribavirin treatment
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A critical review of human endotoxin administration as an experimental paradigm of depression.
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Short-term improvement in insomnia symptoms predicts long-term improvements in sleep, pain, and fatigue in older adults with comorbid osteoarthritis and insomnia
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Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system
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Expression of toll-like receptors in peripheral blood mononuclear cells and response to cognitive-behavioral therapy in major depressive disorder
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Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats
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Unsaturated fatty acids are inversely associated and n-6/n-3 ratios are positively related to inflammation and coagulation markers in plasma of apparently healthy adults
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Delayed response and lack of habituation in plasma interleukin-6 to acute mental stress in men
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Exercise Training as a Treatment for Chronic Inflammation in the Elderly
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Fasting in mood disorders: neurobiology and effectiveness. A review of the literature
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Depressive symptoms enhance stress-induced inflammatory responses.
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Association Study of the Interleukin-1beta (C-511T) Genetic Polymorphism with Major Depressive Disorder, Associated Symptomatology, and Antidepressant Response
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Adherence to the Mediterranean Diet Is Inversely Associated With Circulating Interleukin-6 Among Middle-Aged Men: A Twin Study
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Cognitive-behavioral therapy for sleep disturbance decreases inflammatory cytokines and oxidative stress in hemodialysis patients
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Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice
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Inflammatory and Metabolic Dysregulation and the 2-Year Course of Depressive Disorders in Antidepressant Users
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Are there bi-directional associations between depressive symptoms and C-reactive protein in mid-life women?
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Childhood Abuse and Inflammatory Responses to Daily Stressors
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The inflammatory response following delivery is amplified in women who previously suffered from major depression, suggesting that major depression is accompanied by a sensitization of the inflammatory response system
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Authors: Kiecolt-Glaser, J. K., Derry, H. M., & Fagundes, C. P.
Affiliations: From the Institute for Behavioral Medicine Research and the Department of Psychiatry and Behavioral Health, Ohio State University College of Medicine, Columbus; and the Department of Health Disparities Research, University of Texas MD Anderson Cancer Center, Houston.
The University of Texas MD Anderson Cancer Center (US)
ORCID: Derry, Heather M.
Fagundes, Christopher P.
Venue: American Journal of Psychiatry
Publisher: American Psychiatric Association Publishing
Published: 2015-11-01
Volume: 172
Issue: 11
Pages: 1075-1091
ISSN: 0002-953X (ISSN-L)
1535-7228
DOI: 10.1176/appi.ajp.2015.15020152
PMC: PMC6511978
OpenAlex: W2159036260
Cited by: 844
References: 203
Citations by year: 2026: 61 · 2025: 117 · 2024: 109 · 2023: 93 · 2022: 91 · 2021: 83 · 2020: 58 · 2019: 77 · 2018: 78 · 2017: 47 · 2016: 26 · 2015: 4
FWCI: 2.91
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: American Journal of Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA186720, CA186251, CA172296, K05CA172296, R01CA186251, CA186720)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: depression, inflammation, cytokines, sickness behavior, childhood adversity, obesity, gut microbiota, intestinal permeability, stress response, diet, anti-inflammatory therapy, omega-3 fatty acids, celecoxib, physical activity, depression recurrence
MeSH terms: Gastrointestinal Microbiome, Adult Survivors of Child Adverse Events, Depression, Major Depressive Disorder, Humans, Inflammation, Intestinal Mucosa, Obesity, Permeability, Stress, Psychological, Health Behavior, Cytokines, Dysbiosis

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Inflammation: Depression Fans the Flames and Feasts on the Heat

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