Elevated ratio of arachidonic acid to long-chain omega-3 fatty acids predicts depression development following interferon-alpha treatment: Relationship with interleukin-6

Cross-sectional studies have found that an elevated ratio of arachidonic acid to omega-3 fatty acid is associated with depression, and controlled intervention studies have found that decreasing this ratio through administration of omega-3 fatty acids can alleviate depressive symptoms. Additionally, arachidonic acid and omega-3 fatty acids have opposing effects on inflammatory signaling. Exogenous administration of the inflammatory cytokine interferon-alpha (IFN-alpha) can trigger a depressive episode in a subset of vulnerable people, though associated risk factors remain poorly understood. Using a within-subject prospective design of 138 subjects, we examined whether baseline long-chain omega-3 (docosahexaenoic acid - DHA; eicosapentaenoic acid - EPA) and omega-6 (arachidonic acid - AA; di-homo-gamma-linolenic acid - DGLA) fatty acid status was associated with depression vulnerability in hepatitis C patients treated with IFN-alpha. Based on the literature, we had specific a priori interest in the AA/EPA + DHA ratio. Lower baseline DHA predicted depression incidence (p = 0.04), as did elevated DGLA (p = 0.02) and an elevated AA/EPA + DHA ratio (p = 0.007). The AA/EPA + DHA ratio predicted depression even when controlling for other critical variables such as sleep quality and race. A higher AA/EPA + DHA ratio was positively associated with both increasing Montgomery-Asperg Depression Rating Scores over time (F = 4.0; p < 0.05) as well as interleukin-6 levels (F = 107.4; p < 0.05) but not C-reactive protein. Importantly, omega-3 and omega-6 fatty acid status was not associated with sustained viral response to IFN-alpha, treatment. These prospective data support the role of fatty acid status in depression vulnerability and indicate a potential role for omega-3 fatty acids in the prevention of inflammation-induced depression. (c) 2012 Elsevier Inc. All rights reserved.