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Clinical Efficacy and Biological Regulations of ω–3 PUFA-Derived Endocannabinoids in Major Depressive Disorder
Yang B.1,2; Lin L.3; Bazinet R.P.3; Chien Y.-C.2; Chang J.P.-C.2; Satyanarayanan S.K.2,4; Su H.4; Su K.-P.1,2,5

Background: Endocannabinoids (ECs) are one type of bioactive endogenous neuroinflammatory mediator derived from polyunsaturated fatty acids (PUFAs), which may regulate the emotional processes. Here, we assessed the effect of ω–3 PUFAs on EC levels, which may be the novel targets for the ω–3 PUFAs’ antidepressive effects. Methods: We conducted a 12-week double-blind, nonplacebo, randomized controlled trial. Eighty-eight major depressive disorder (MDD) participants were randomly assigned to receive eicosapentaenoic acid (EPA, 3.0 g/day), docosahexaenoic acid (DHA, 1.4 g/day), or a combination of EPA (1.5 g/d) and DHA (0.7 g/day). Eighty-five participants completed the trial, and their clinical remission and plasma PUFA-derived EC levels (pmol/mL) were measured. Results: The cumulative rates of clinical remission were significantly higher in the EPA and EPA + DHA groups than the DHA group (51.85 and 53.84 vs. 34.37%; p =0.027 and p =0.024, respectively). EPA and EPA + DHA treatments increased the eicosapentaenoylethanolamide (EPEA) levels compared to DHA treatment (0.33 ± 0.18 and 0.35 ± 0.24 vs. 0.08 ± 0.12; p =0.002 and p =0.001, respectively), while EPA + DHA treatment increased the docosahexaenoylethanolamide levels more than EPA treatment (1.34 ± 2.09 vs. 0.01 ± 1.79; p =0.006). Plasma EPEA levels were positively correlated with rates of clinical remission (hazard ratio: 1.60, 95% confidence interval: 1.08–2.39). Conclusions: Treatments enriched with EPA increased plasma EPEA levels, which was positively associated with clinical remission. This finding may suggest that levels of plasma EPEA play a potential novel endogenous therapeutic target in MDD.

KeywordDocosahexaenoic Acid Eicosapentaenoic Acid Endocannabinoids Major Depressive Disorder Ω–3 Polyunsaturated Fatty Acid
Indexed BySCI
WOS Research AreaPsychiatry ; Psychology
WOS SubjectPsychiatry ; Psychology
WOS IDWOS:000481456900003
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Institute of Lipids Medicine and School of Public Health, Wenzhou Medical University, Wenzhou, China
2.Department of Psychiatry and Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan
3.Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada
4.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
5.College of Medicine, China Medical University, Taichung, Taiwan
Recommended Citation
GB/T 7714
Yang B.,Lin L.,Bazinet R.P.,et al. Clinical Efficacy and Biological Regulations of ω–3 PUFA-Derived Endocannabinoids in Major Depressive Disorder[J]. PSYCHOTHERAPY AND PSYCHOSOMATICS,2019,88(4):215-224.
APA Yang B..,Lin L..,Bazinet R.P..,Chien Y.-C..,Chang J.P.-C..,...&Su K.-P..(2019).Clinical Efficacy and Biological Regulations of ω–3 PUFA-Derived Endocannabinoids in Major Depressive Disorder.PSYCHOTHERAPY AND PSYCHOSOMATICS,88(4),215-224.
MLA Yang B.,et al."Clinical Efficacy and Biological Regulations of ω–3 PUFA-Derived Endocannabinoids in Major Depressive Disorder".PSYCHOTHERAPY AND PSYCHOSOMATICS 88.4(2019):215-224.
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