Our study provides further evidence for the presence of qualitatively different SAD subgroups and the propensity of a subset of people with SAD to exhibit impulsive, high-risk behaviors.

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...

Objective: Depression has been associated with hepatitis C, as well as with its treatment with proinflammatory cytokines (i.e., interferon). The new direct-acting antiviral agents (DAAs) have minimal adverse effects and high potency, with a direct inhibitory effect on non-structural viral proteins. We studied the incidence and associated factors of depression in a real-life prospective cohort of chronic hepatitis C patients treated with the new DAAs. Methods: The sample was recruited from a cohort of 91 patients with hepatitis C, of both sexes, with advanced level of fibrosis and no HIV coinfection, consecutively enrolled during a 6-month period for DAA treatment; those euthymic at baseline (n=54) were selected. All were evaluated through the depression module of the Patient Health Questionnaire (PHQ-9-DSM-IV), at three time points: baseline, 4 weeks, and end-of-treatment. Results: The cumulative incidence (95%CI) of major depression and any depressive disorder during DAA treatment was 13% (6.4-24.4) and 46.3% (33.7-59.4), respectively. No differences were observed between those patients with and without cirrhosis or ribavirin treatment (p 4 0.05). Risk factors for incident major depression during DAA treatment included family depression (relative risk 9.1 [1.62-51.1]), substance use disorder (11.0 [1.7-73.5]), and baseline PHQ-9 score (2.1 [1.1-3.1]). Conclusions: The findings of this study highlight the importance of screening for new depression among patients receiving new DAAs, and identify potential associated risk factors.