1. Omega-3 fatty acids in the prevention of interferon-alpha-induced depression Kuan-Pin Su, M.D., Ph.D.a, c, e,,, Hsueh-Chou Lai, M.D.b, Hui-Ting Yang, Ph.D.d, Wen-Pang Su, M.D.b, Cheng-Yuan Peng, M.D., Ph.D.b, Jane Pei-Chen Chang, M.D., M.S.a, Hui-Chih Chang, M.Sc.a, Carmine M. Pariante, M.D., Ph.D, FRCPsych.e, presentation by Qiujing Hu

2. Page  2 study the benifits of omega 3 fatty acids for the prevention and delay of interferon therapy of hepatitis C induced depression  what is hepatitis C? Hepatitis C is an infectious disease affecting primarily the liver, caused by the hepatitis C virus (HCV).  treatment Interferon (IFN)-α IFNs belong to the large class of glycoproteins known as cytokines. Interferons are named after their ability to "interfere" with viral replication within host cells.  side effects interferon therapy is highly associated with depression. treatments with antidepressants might expose patients to adverse effects, therefore, alternative of antidepressants is needed.  treatment of side effect Omega-3 polyunsaturated fatty acids (PUFAs) has been found to be a safe and effective treatment of depression, and is workded through an anti-inflammatory action. introduction/background

3. the purpose of this papaer is to studies the effects of omega-3 PUFAs, EPA and DHA to prevent IFN induced depression hypothesis: the effects of the omega-3 PUFAs, EPA and DHA, against placebo can prevent IFN-α-induced depression. rationale Rationale the purpose of this papaer is to studies the effects of omega-3 PUFAs, EPA and DHA to prevent IFN alpha induced depression Hypothesis: the effects of the omega-3 PUFAs, EPA and DHA, against placebo can prevent IFN-α-induced depression.

4. Page  4 methods  Doule-blind, placebo-controlled trial  3 tials: comparing EPA; DHA or placebo  152 randomized paitient were given treatment for 2 weeks and were followed throughout the 24 weeks of IFN-α treatment, and these paitients are included in the analysis  The recruited participants were evaluated at weeks –2 (when omega- 3 fatty acid intervention started), and every 2 week when the intervention stopped and therapy started, to monitor the occurrence of major depressive episode.

5. Page  5 results incident rates of IFN-induced depression

6. Page  6 results  Survival curves (Kaplan-Meier estimates) of cumulative incidences of IFN- induced depression of 152 patients with hepatitis C viral infection who were pre-treated with EPA (n=50), DHA (n=51) or placebo (n=51) for 2 weeks before a 24-week IFN-α therapy.

7. Page  7 results  In the overall sample, a total of 34 patients (22%) developed IFN-α- induced depression at some point during the 24-week therapy, while 118 (78%) patients did not develop IFN-α-induced depression. At week -2 (before the intervention), subjects who later developed IFN-α-induced depression had lower baseline EPA levels than those who did not, but not DHA levels. However, at week 0, there were no significant differences in EPA or DHA levels between subjects who did or did not develop IFN- alpha-induced depression.

8. Page  8 discussion  overall findings: The main finding is that EPA pre-treatment significantly decreased the incidence of IFN-α-induced depression in HCV patients. both EPA and DHA pre-treatment significantly delayed the onset of IFN-α- induced depression as compared to placebo pre-treatment.  EPA can be metabolised into DHA  These results therefore indicate EPA and DHA work together to lower depression symptoms.

9. Page  9 discussion  why the pro-inflammatory cytokines promotes depression  IDO pathway produces depressive metabolites. EPA has numerous anti-inflammatory properties: prevents membrane AA formation inhibits COX2 enzyme activity reduces PGE2 synthesis

10. Page  10 conclusion  In conclusion, EPA was beneficial for the prevention of IFN-α-induced depression, while DHA had only modest effects on delaying the onset. The data suggest that EPA or EPA/DHA combination is the best preventive strategy in this group of patients, and potentially a suitable strategy for the wider pool of patients with depression associated with inflammation.