title: Elevated ratio of arachidonic acid to long-chain omega-3 fatty acids predicts depression development following interferon-alpha treatment: relationship with interleukin-6.
abstract: 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.
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. lotrichfe@upmc.edu
authors.forename: Francis E
authors.initials: FE
authors.lastname: Lotrich
authors.forename: Barry
authors.initials: B
authors.lastname: Sears
authors.forename: Robert K
authors.initials: RK
authors.lastname: McNamara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016718:Arachidonic Acid / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D003866:Depressive Disorder / Q000097:blood / Q000209:etiology*; D015525:Fatty Acids, Omega-3 / Q000097:blood*; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D007249:Inflammation / Q000097:blood; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged
chemical_list: D015525:Fatty Acids, Omega-3; D016898:Interferon-alpha; D015850:Interleukin-6; D016718:Arachidonic Acid; D002097:C-Reactive Protein