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Glucocorticoid receptors, brain-derived neurotrophic factor, serotonin and dopamine neurotransmission are associated with interferon-induced depression.

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dc.contributor.author Udina, M. 
dc.contributor.author Navinés, Ricard
dc.contributor.author Egmond, E.  
dc.contributor.author Oriolo, Giovanni
dc.contributor.author Langohr, Klaus
dc.contributor.author Gimenez, Dolors
dc.contributor.author Valdés, M. 
dc.contributor.author Gómez-Gil, E. 
dc.contributor.author Grande, Iria
dc.contributor.author Gratacós Mayora, Mònica
dc.contributor.author Kapczinski, F.  
dc.contributor.author Artigas, Francesc
dc.contributor.author Vieta, Eduard
dc.contributor.author Solà, Rosa
dc.contributor.author Martín Santos, Rocío
dc.date.accessioned 2016-05-23T11:03:00Z
dc.date.available 2016-05-23T11:03:00Z
dc.date.issued 2016
dc.identifier.citation Udina M, Navinés R, Egmond E, Oriolo G, Langohr K, Gimenez D. et al. Glucocorticoid receptors, brain-derived neurotrophic factor, serotonin and dopamine neurotransmission are associated with interferon-induced depression. Int J Neuropsychopharmacol. 2016 Apr 20;19(4). pii: pyv135. doi: 10.1093/ijnp/pyv135
dc.identifier.issn 1461-1457
dc.identifier.uri http://hdl.handle.net/10230/26320
dc.description.abstract BACKGROUND: The role of inflammation in mood disorders has received increased attention. There is substantial evidence that cytokine therapies, such as interferon alpha (IFN-alpha), can induce depressive symptoms. Indeed, proinflammatory cytokines change brain function in several ways, such as altering neurotransmitters, the glucocorticoid axis, and apoptotic mechanisms. This study aimed to evaluate the impact on mood of initiating IFN-alpha and ribavirin treatment in a cohort of patients with chronic hepatitis C. We investigated clinical, personality, and functional genetic variants associated with cytokine-induced depression. METHODS: We recruited 344 Caucasian outpatients with chronic hepatitis C, initiating IFN-alpha and ribavirin therapy. All patients were euthymic at baseline according to DSM-IV-R criteria. Patients were assessed at baseline and 4, 12, 24, and 48 weeks after treatment initiation using the Patient Health Questionnaire (PHQ), the Hospital Anxiety and Depression Scale (HADS), and the Temperament and Character Inventory (TCI). We genotyped several functional polymorphisms of interleukin-28 (IL28B), indoleamine 2,3-dioxygenase (IDO-1), serotonin receptor-1A (HTR1A), catechol-O-methyl transferase (COMT), glucocorticoid receptors (GCR1 and GCR2), brain-derived neurotrophic factor (BDNF), and FK506 binding protein 5 (FKBP5) genes. A survival analysis was performed, and the Cox proportional hazards model was used for the multivariate analysis. RESULTS: The cumulative incidence of depression was 0.35 at week 24 and 0.46 at week 48. The genotypic distributions were in Hardy-Weinberg equilibrium. Older age (p = 0.018, hazard ratio [HR] per 5 years = 1.21), presence of depression history (p = 0.0001, HR = 2.38), and subthreshold depressive symptoms at baseline (p = 0.005, HR = 1.13) increased the risk of IFN-induced depression. So too did TCI personality traits, with high scores on fatigability (p = 0.0037, HR = 1.17), impulsiveness (p = 0.0200 HR = 1.14), disorderliness (p = 0.0339, HR = 1.11), and low scores on extravagance (p = 0.0040, HR = 0.85). An interaction between HTR1A and COMT genes was found. Patients carrying the G allele of HTR1A plus the Met substitution of the COMT polymorphism had a greater risk for depression during antiviral treatment (HR = 3.83) than patients with the CC (HTR1A) and Met allele (COMT) genotypes. Patients carrying the HTR1A CC genotype and the COMT Val/Val genotype (HR = 3.25) had a higher risk of depression than patients with the G allele (HTR1A) and the Val/Val genotype. Moreover, functional variants of the GCR1 (GG genotype: p = 0.0436, HR = 1.88) and BDNF genes (Val/Val genotype: p = 0.0453, HR = 0.55) were associated with depression. CONCLUSIONS: The results of the study support the theory that IFN-induced depression is associated with a complex pathophysiological background, including serotonergic and dopaminergic neurotransmission as well as glucocorticoid and neurotrophic factors. These findings may help to improve the management of patients on antiviral treatment and broaden our understanding of the pathogenesis of mood disorders.
dc.description.sponsorship This study was funded by the following Spanish grants: Instituto de Carlos III, Fondo de Investigaciones Sanitarias PSICOCITVHC-P110/01827 and PSIGEN-VHC-EC08/00201 (Dr MartínSantos). It was co-financed by the ERDF, European Union “One way to make Europe,” Ministerio de Economía y Competitividad (MTM2012-38067-C02-01), and the support of the Generalitat de Catalunya (SGR2009/1435/SGR2014/1411; Dr Martín-Santos). Dr Grande has received a research grant from Río Hortega Contract (CM12/00062), Instituto de Salud Carlos III, Spanish Ministry of Economy and Competiveness.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartof The International Journal of Neuropsychopharmacology. 2016 Apr 20;19(4)
dc.rights © The Author 2015. Published by Oxford University Press on behalf of CINP. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium,provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.subject.other Depressió psíquica
dc.subject.other Hepatitis C
dc.subject.other Personalitat
dc.title Glucocorticoid receptors, brain-derived neurotrophic factor, serotonin and dopamine neurotransmission are associated with interferon-induced depression.
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1093/ijnp/pyv135
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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