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Risk factors for the development of depression in patients with hepatitis C taking interferon-?.

ABSTRACT: Interferon-?, currently used for the treatment of hepatitis C, is associated with a substantially elevated risk of depression. However, not everyone who takes this drug becomes depressed, so it is important to understand what particular factors may make some individuals more 'at risk' of developing depression than others. Currently there is no consensus as to why interferon-induced depression occurs and the range of putative risk factors is wide and diverse. The identification of risk factors prior to treatment may allow identification of patients who will become depressed on interferon, allowing the possibility of improved treatment support and rates of treatment adherence. Here, we consolidate and review the literature on risk factors, and we discuss the potential confounds within the research examined in order to better isolate the risk factors that may be important in the development of depression in these patients and which might help predict patients likely to become depressed on treatment. We suggest that interactions between psychobehavioral, genetic, and biological risk factors are of particular importance in the occurrence of depression in patients with hepatitis C taking interferon-?.

SUBMITTER: Smith KJ

PROVIDER: S-EPMC3101888 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Risk factors for the development of depression in patients with hepatitis C taking interferon-α.

Smith Kimberley J KJ Norris Suzanne S O'Farrelly Cliona C O'Mara Shane M SM

Neuropsychiatric disease and treatment 20110515

Interferon-α, currently used for the treatment of hepatitis C, is associated with a substantially elevated risk of depression. However, not everyone who takes this drug becomes depressed, so it is important to understand what particular factors may make some individuals more 'at risk' of developing depression than others. Currently there is no consensus as to why interferon-induced depression occurs and the range of putative risk factors is wide and diverse. The identification of risk factors pr ...[more]

PMID: 21654873

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Project description:Importance: The high incidence of major depressive episodes during interferon-α (IFN-α) therapy is considered the most powerful supportive evidence for the inflammation theory of depression. As the kynurenine pathway plays an important role connecting inflammation and depression, it is plausible to investigate this pathway for predictive genetic markers for IFN-α-induced depression. Methods: In this prospective case-control study, we assessed 291 patients with chronic hepatitis C viral infection taking IFN-α therapy and analyzed the single nucleotide polymorphisms (SNPs) in genes in the kynurenine pathway. Our case group contained patients who developed IFN-α-induced depression during the treatment, and others were defined as the control group. Genomic DNA was extracted from leukocytes in the peripheral blood and analyzed by Affymetrix TWB array. We first tested allelic, dominant, and recessive models on each of our SNPs using Fisher's exact test. We then conducted 5000 gene-wide max(T) permutations based on the best model of each SNP to provide strong gene-wide family-wise error rate control. Finally, we preformed logistic regression for the significant SNPs acquired in previous procedures, with sex and education level as covariates to build predictive models. Additional haplotype analyses were conducted with Haploview 4.2 to investigate the combining effect of multiple significant SNPs within a gene. Results: With sex and education level as covariates, rs8082252 (p = 0.0015, odds ratio = 2.716), rs8082142 (p = 0.0031, odds ratio = 2.499) in arylformamidase (AFMID), and rs12477181 (p = 0.0004, odds ratio = 0.3478) in kynureninase (KYNU) were significant in logistic regression models with dominant modes of inheritance. Haplotype analyses showed the two significant SNPs in AFMID to be in the same haploblock and highly correlated (r2 = 0.99). There were two significant haplotypes (by the sequence of rs8082252, rs8082142): AT (χ2 = 7.734, p = 0.0054) and GC (χ2 = 6.874, p = 0.0087). Conclusions: This study provided supportive evidence of the involvement of the kynurenine pathway in IFN-α-induced depression. SNPs in this pathway were also predictive of this disease.

Dataset Information

Risk factors for the development of depression in patients with hepatitis C taking interferon-?.

Publications

Risk factors for the development of depression in patients with hepatitis C taking interferon-α.

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