69. Endocannabinoid alterations in interferon-alpha induced depression

• Published in: Brain, behavior, and immunity Vol. 40; pp. e20 - e21
• Main Authors: Zajkowska, Z, Cattaneo, A, Zunszain, P.A, Hepgul, N, Russell, A, Borsini, A, Pariante, C.M
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2014
• Subjects: Allergy and Immunology; Psychiatry
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2014.06.089

Current treatment for chronic hepatitis C (HCV) viral infection, interferon- α (IFN-α), has been shown to induce depression in more than 30% of patients. We investigated whether genes belonging to the endocannabinoid (eCB) system are involved in mechanisms underlying depression development. We recruited 50 HCV patients receiving IFN-α treatment and assessed them at treatment weeks 0, 4 and 24. We used M.I.N.I. International Neuropsychiatric Interview to follow depression and analysed mRNA levels of selected eCB related genes using Affymetrix® Human Gene 1.1ST Array. NAPE-PLD and DAGL-α – coding for enzymes involved in eCB synthesis – were lower at baseline in those who developed depression vs those who did not (−17%, p = 0.02; −17%, p = 0.003; respectively). After 4 weeks, levels of CNR2 – coding for eCB CB2 receptors – were reduced (−21%, p < 0.001), while levels of FAAH2 – coding for a degrading eCB enzyme – and DAGL-α were increased in the whole sample (+19%, p = 0.01, +19%, p < 0.001, respectively). After controlling for depression development, FAAH2 levels were significantly increased in depressed patients only (+25%, p = 0.005). From baseline to week 24, CNR2 levels decreased in non-depressed patients (−29%, p < 0.001). Interestingly, at week 24 CNR2 levels were higher in depressed compared with non-depressed individuals (+27%, p = 0.001). Our findings suggest that alterations in the eCB system may underlie the increased vulnerability for depression development in HCV infected patients treated with IFN-α.