title: Altered soluble epoxide hydrolase-derived oxylipins in patients with seasonal major depression: An exploratory study.
abstract: 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.
authors.affiliation: Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA. Electronic address: mhennebelle@ucdavis.edu.
authors.forename: Marie
authors.initials: M
authors.lastname: Hennebelle
authors.affiliation: Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA; Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi, Japan. Electronic address: yotoki@ucdavis.edu.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Otoki
authors.affiliation: Department of Entomology and Nematology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA. Electronic address: junyang@ucdavis.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Entomology and Nematology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA. Electronic address: bdhammock@ucdavis.edu.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada. Electronic address: anthony.levitt@sunnybrook.ca.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Levitt
authors.affiliation: Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA. Electronic address: ataha@ucdavis.edu.
authors.forename: Ameer Y
authors.initials: AY
authors.lastname: Taha
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON Canada. Electronic address: w.swardfager@utoronto.ca.
authors.forename: Walter
authors.initials: W
authors.lastname: Swardfager
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000097:blood* / Q000523:psychology; D004851:Epoxide Hydrolases; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007249:Inflammation / Q000097:blood; D008041:Linoleic Acids / Q000097:blood; D008297:Male; D008875:Middle Aged; D054883:Oxylipins / Q000097:blood*; D016574:Seasonal Affective Disorder / Q000097:blood* / Q000523:psychology; D012621:Seasons; D053719:Tandem Mass Spectrometry
chemical_list: D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D008041:Linoleic Acids; D054883:Oxylipins; C024348:13-hydroxy-9,11-octadecadienoic acid; D004851:Epoxide Hydrolases
keywords: Cytochrome p450; Depression; Fatty acids; Lipidomics; Omega-3; Omega-6; Oxylipins; Seasonal major depression; Soluble epoxide hydrolase