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

Brain Behav Immun. 2013 Jul;31:48-53. doi: 10.1016/j.bbi.2012.08.007. Epub 2012 Aug 19.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arachidonic Acid / blood*
  • C-Reactive Protein / metabolism
  • Depressive Disorder / blood
  • Depressive Disorder / etiology*
  • Fatty Acids, Omega-3 / blood*
  • Female
  • Hepatitis C / drug therapy
  • Humans
  • Inflammation / blood
  • Interferon-alpha / adverse effects*
  • Interferon-alpha / therapeutic use
  • Interleukin-6 / blood*
  • Male
  • Middle Aged

Substances

  • Fatty Acids, Omega-3
  • Interferon-alpha
  • Interleukin-6
  • Arachidonic Acid
  • C-Reactive Protein