Serotonin and interleukin-6: The role of genetic polymorphisms in IFN-induced neuropsychiatric symptoms

Udina, Marc; Moreno-España, J.; Navinés, Ricard; Giménez, Dolors; Langohr, Klaus; Gratacòs, Mónica; Capuron, Lucile; Torre, Rafael de la; Solá, Ricard; Martín‐Santos, Rocío

doi:10.1016/j.psyneuen.2013.03.007

Cited by 54 publications

(34 citation statements)

References 52 publications

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“…Following immune challenges such as these, depression is more likely to develop among healthy adults with an MDD history, greater initial depressive symptoms, low social support, and susceptible genetic profiles than those without these risk factors [17, 19, 20]. Notably, women are more likely to have a depression history, which elevates risk for subsequent depression following inflammatory challenges.…”

Section: Inflammation: a Pathway To Depressionmentioning

confidence: 99%

Sex Differences in Depression: Does Inflammation Play a Role?

Derry

Padin

Kuo

et al. 2015

Curr Psychiatry Rep

142

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Women become depressed more frequently than men, a consistent pattern across cultures. Inflammation plays a key role in initiating depression among a subset of individuals, and depression also has inflammatory consequences. Notably, women experience higher levels of inflammation and greater autoimmune disease risk compared to men. In the current review, we explore the bidirectional relationship between inflammation and depression and describe how this link may be particularly relevant for women. Compared to men, women may be more vulnerable to inflammation-induced mood and behavior changes. For example, transient elevations in inflammation prompt greater feelings of loneliness and social disconnection for women than for men, which can contribute to the onset of depression. Women also appear to be disproportionately affected by several factors that elevate inflammation, including prior depression, somatic symptomatology, interpersonal stressors, childhood adversity, obesity, and physical inactivity. Relationship distress and obesity, both of which elevate depression risk, are also more strongly tied to inflammation for women than for men. Taken together, these findings suggest that women’s susceptibility to inflammation and its mood effects may contribute to sex differences in depression. Depression continues to be a leading cause of disability worldwide, with women experiencing greater risk than men. Due to the depression-inflammation connection, these patterns may promote additional health risks for women. Considering the impact of inflammation on women’s mental health may foster a better understanding of sex differences in depression, as well as the selection of effective depression treatments.

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Section: Inflammation: a Pathway To Depressionmentioning

confidence: 99%

Sex Differences in Depression: Does Inflammation Play a Role?

Derry

Padin

Kuo

et al. 2015

Curr Psychiatry Rep

142

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“…The -174 SNP (rs1800795) is particularly interesting since individuals who carry the G allele have higher plasma concentrations of IL-6 (Zakharyan et al 2012) and the polymorphism has been studied as a modulator of interferon-induced depression. Patients who carried the C allele (low synthesising IL-6) were reported to show fewer depressive and anxiety symptoms than those carrying the G allele, after beginning treatment with IFN-a (Bull et al 2009;Udina et al 2013). However, only a small study investigated the potential role of the SNP in MDD and it reported negative findings (Clerici et al 2009), while an additional study reported no association between MDD and the SNP at -634 in a Chinese population (Hong et al 2005).…”

Section: Interleukin-6mentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under-or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in anti-depressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-a receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

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“…It has been shown that the G allele is associated with higher plasma concentrations of IL-6 during immune activation than the C allele (Fishman et al 1998). It has been shown that “high IL-6” genotype is associated with more depressive symptoms during IFN-α treatment in CHC patients (Bull et al 2009; Udina et al 2013). This finding is consistent with the evidence that plasma IL-6 positively is associated with depressive symptoms among patients without any immune-modulatory treatment (Liu et al 2012) as well as among patients during IFN-α treatment (Bonaccorso et al 2001; Prather et al 2009; Wichers et al 2007) including CHC patients (Udina et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Several genetic polymorphisms have been analyzed to identify increased risk factors for developing depression in the course of IFN-α treatment, including serotonin transporter gene ( 5 - HTTLPR ) (Bull et al 2009), 5-HT1A receptor gene (Kraus et al 2007), tryptophan hydroxylase-2 gene ( TPH2 ) (Kraus et al 2007), phospholipase A2 ( PLA2 ) and cyclooxygenase 2 ( COX2 ) gene (Su et al 2010). Additionally, with respect to immune system the following genes have been analyzed: IFN-α/β receptor 1 ( IFNAR1 ) gene (Smith et al 2012), IL-6 gene ( IL6 ) (Bull et al 2009; Udina et al 2013), IL-1 α and β ( IL1A, IL1B ) genes (Smith et al 2012), IFN-γ ( IFNG ) gene (Oxenkrug et al 2011) as well as genes encoding IL28B (Pasha et al 2013), TGF-β1 (Pasha et al 2013) and TNF-α (Pasha et al 2013). Moreover, recently 15 genes were identified that were selectively hyper-responsive to exogenous IFN-α in patients that developed depressive side effects (Schlaak et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Functional Polymorphism in the Interleukin 6 (IL6) Gene with Respect to Depression Induced in the Course of Interferon-α and Ribavirin Treatment in Chronic Hepatitis Patients

Frydecka

Pawłowski

Pawlak

et al. 2016

Arch. Immunol. Ther. Exp.

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Interleukin (IL)-6 is a multifactorial cytokine known to be increased in patients with chronic hepatitis C (CHC) and to be predictive of depression incidence. The aim of the study was to explore the association between IL6 gene C-174G polymorphism and depressive symptom severity in the longitudinal study design following the course of pegylated interferon/ribavirin treatment in CHC patients. In our study, we included 62 CHC subjects. They were assessed using present state examination, Beck Depression Inventory (BDI) and Montgomery Åsberg Depression Rating Scale (MADRS) at weeks 0, 3, 5, 9, 13, 24 and 24 weeks after the end of treatment. The risk of depression was associated with higher baseline MADRS score and BDI score. Interestingly, when stratified by IL6 C-174G polymorphism, higher baseline depressive symptom severity measured by MADRS and BDI predicted higher risk of depression in the course of antiviral treatment only in high IL-6 producers—G allele carriers (patients with GG and CG genotypes) (p = 0.004, p = 0.00008, respectively). There is interaction between severity of baseline depressive symptoms at the beginning of antiviral therapy and IL6 gene C-174G polymorphism leading to increased risk for the development of depressive episode in CHC patients in the course of antiviral treatment.

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Serotonin and interleukin-6: The role of genetic polymorphisms in IFN-induced neuropsychiatric symptoms

Cited by 54 publications

References 52 publications

Sex Differences in Depression: Does Inflammation Play a Role?

Sex Differences in Depression: Does Inflammation Play a Role?

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Functional Polymorphism in the Interleukin 6 (IL6) Gene with Respect to Depression Induced in the Course of Interferon-α and Ribavirin Treatment in Chronic Hepatitis Patients

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