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

• Published in: Brain, behavior, and immunity Vol. 31; pp. 48 - 53
• Main Authors: Lotrich, Francis E., Sears, Barry, McNamara, Robert K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.07.2013
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Allergy and Immunology; Arachidonic acid; Arachidonic Acid - blood; C-reactive protein; C-Reactive Protein - metabolism; Cytokine; Depressive Disorder - blood; Depressive Disorder - etiology; Fatty Acids, Omega-3 - blood; Female; Hepatitis C - drug therapy; Humans; Inflammation; Inflammation - blood; Interferon-alpha - adverse effects; Interferon-alpha - therapeutic use; Interleukin-6; Interleukin-6 - blood; Major depressive disorder; Male; Middle Aged; Omega-3 fatty acids; Psychiatry; C-reactive protein; Cytokine; Inflammation; Arachidonic acid; Omega-3 fatty acids; Major depressive disorder; Interleukin-6
• ISSN: 0889-1591; 1090-2139; 1090-2139
• DOI: 10.1016/j.bbi.2012.08.007

► Elevated omega-6 fatty acids and lower omega-3 fatty acids were found to increase the risk for depression in people being treated with interferon-alpha. 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-α) 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-α. 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-α 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.