Trial reportMolecular psychiatry2009
Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.
Trial report in Molecular psychiatry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 6 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
106 citing papers in PubMed, 6 syntheses or guidelines pooled it, 228 citations in OpenAlex.
- Impact of parasitic infection on mental health and illness in humans in Africa: a systematic review.Parasitology · 2022Pooled it
- A systematic review of the association between fatigue and genetic polymorphisms.Brain, behavior, and immunity · 2017Pooled it
- Genetic Contributions of Inflammation to Depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Pooled it
- Sirukumab: A Potential Treatment for Mood Disorders?Advances in therapy · 2017Pooled it
- The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation.Archives of general psychiatry · 2011Pooled it
- Antidepressant response and the serotonin transporter gene-linked polymorphic region.Biological psychiatry · 2010Pooled it
- Moderators for depressed mood and systemic and transcriptional inflammatory responses: a randomized controlled trial of endotoxin.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Trial
- Absolute Measurements of Macrophage Migration Inhibitory Factor and Interleukin-1-β mRNA Levels Accurately Predict Treatment Response in Depressed Patients.The international journal of neuropsychopharmacology · 2016Trial
- Trial
- Neurobehavioral effects of interferon-α in patients with hepatitis-C: symptom dimensions and responsiveness to paroxetine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Trial
- Selective hyper-responsiveness of the interferon system in major depressive disorders and depression induced by interferon therapy.PloS one · 2012Trial
- Early activation of p38 mitogen activated protein kinase is associated with interferon-alpha-induced depression and fatigue.Brain, behavior, and immunity · 2011Trial
- Citalopram reduces endotoxin-induced fatigue.Brain, behavior, and immunity · 2011Trial
- The interaction between the immune system and the autonomic nervous system in the pathophysiology of major depressive disorder: a scoping review.Brain, behavior, & immunity - health · 2026Review
- Interferon signaling pathways in health and disease.Molecular biomedicine · 2025Review
- Medium-Chain Triglyceride Administration Induces Antidepressant Effects in Animal Models by Increasing Beta-Hydroxybutyrate Levels.Yonago acta medica · 2025Article
- Systemic inflammation and cancer-related frailty: shifting the paradigm toward precision survivorship medicine.ESMO open · 2024Article
- Article
- Evaluating Associations between Average Pain Intensity and Genetic Variation in People with Sickle Cell Disease: An Exploratory Study.Pain management nursing : official journal of the American Society of Pain Management Nurses · 2023Article
- FermentedInternational journal of molecular sciences · 2022Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King's College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The 'low IL-6' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The 'high transcription' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the 'protective' effect of the 5-HTTLPR polymorphism was evident only in the presence of the 'low IL-6' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the 'high IL-6' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role of the inflammatory response system in the pathophysiology of IFN-alpha-induced depression; in contrast, the effect of the 5-HTT gene was small and perhaps dependent on the status of the inflammatory response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.