Altered soluble epoxide hydrolase-derived oxylipins in patients with seasonal major depression: An exploratory study

Marie Hennebelle, Yurika Otoki, Jun Yang, Bruce D. Hammock, Anthony J. Levitt, Ameer Y. Taha, Walter Swardfager

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


Many cytochrome p450-derived lipids promote resolution of inflammation, in contrast to their soluble epoxide hydrolase(sEH)-derived oxylipin breakdown products. Here we compare plasma oxylipins and precursor fatty acids between seasons in participants with major depressive disorder with seasonal pattern (MDD-s). Euthymic participants with a history of MDD-s recruited in summer-fall were followed-up in winter. At both visits, a structured clinical interview (DSM-5 criteria) and the Beck Depression Inventory II (BDI-II) were administered. Unesterified and total oxylipin pools were assayed by liquid chromatography tandem mass-spectrometry (LC-MS/MS). Precursor fatty acids were measured by gas chromatography. In nine unmedicated participants euthymic at baseline who met depression criteria in winter, BDI-II scores increased from 4.9±4.4 to 19.9±7.7. Four sEH-derived oxylipins increased in winter compared to summer-fall with moderate to large effect sizes. An auto-oxidation product (unesterified epoxyketooctadecadienoic acid) and lipoxygenase-derived 13-hydroxyoctadecadienoic acid also increased in winter. The cytochrome p450-derived 20-COOH-leukotriene B4 (unesterified) and total 14(15)-epoxyeicosatetraenoic acid, and the sEH-derived 14,15-dihydroxyeicostrienoic acid (unesterified), decreased in winter. We conclude that winter depression was associated with changes in cytochrome p450- and sEH-derived oxylipins, suggesting that seasonal shifts in omega-6 and omega-3 fatty acid metabolism mediated by sEH may underlie inflammatory states in symptomatic MDD-s.

Original languageEnglish
Pages (from-to)94-101
Number of pages8
JournalPsychiatry Research
Publication statusPublished - 2017 Jun 1


  • Cytochrome p450
  • Depression
  • Fatty acids
  • Lipidomics
  • Omega-3
  • Omega-6
  • Oxylipins
  • Seasonal major depression
  • Soluble epoxide hydrolase


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