نبذة مختصرة : Purpose: Major depressive disorder (MDD) is frequently accompanied by the symptoms of clinical anxiety. Since our previous research has found that n-3 PUFA supplementation alleviates anxiety in MDD, this study was aimed to further explore whether n-3 PUFA supplementation improves anxiety symptoms in depression by directly manipulating fatty acid levels.
Methods: A secondary analysis of biomarker data (erythrocyte fatty acid composition) collected as part of the randomized clinical trial which investigated the adjunctive effect of n-3 PUFAs was conducted on 72 venlafaxine-treated outpatients with first-diagnosed, drug-naïve depression. All participants with longitudinal biomarker data were included in the association analysis to determine how n-3 PUFA supplementation influences fatty acid composition and alleviates anxiety symptoms in depression.
Results: Decreases of the C20:3n6 were found in all participants at both follow-up time points (χ 2 = 96.36, p = 0.000). The n-3 index (χ 2 = 10.59, p = 0.001), EPA (χ 2 = 24.31, p = 0.000), and C22:5n3/C20:5n3 ratio (χ 2 = 10.71, p = 0.001) were increased, while C22:4n6 (χ 2 = 7.703, p = 0.006) was decreased in n-3 PUFA group compared to the placebo group. The improvement in anxiety symptoms positively correlates with the extent of reduction of C16:0, C18:0, and total fatty acid levels as well as D5 desaturase activity (p < 0.05).
Conclusion: These data suggest that the anxiolytic effect exerted by n-3 PUFAs in first-diagnosed, drug-naïve depression is manipulated by erythrocyte fatty acid levels. Saturated fatty acid levels have an important role in predicting the severity of anxiety symptoms.
(© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)
References: Belmaker RH, Agam G (2008) Major depressive disorder. N Engl J Med 358:55–68. (PMID: 10.1056/NEJMra07309618172175)
Strine TW, Mokdad AH, Balluz LS et al (2008) Depression and anxiety in the United States: findings from the 2006 behavioral risk factor surveillance system. Psychiatr Serv 59:1383–1390. (PMID: 10.1176/ps.2008.59.12.138319033164)
Tolmunen T, Lehto SM, Julkunen J et al (2014) Trait anxiety and somatic concerns associate with increased mortality risk: a 23-year follow-up in aging men. Ann Epidemiol 24:463–468. (PMID: 10.1016/j.annepidem.2014.03.00124731699)
Gorman JM (1996) Comorbid depression and anxiety spectrum disorders. Depress Anxiety 4:160–168. (PMID: 10.1002/(SICI)1520-6394(1996)4:4<160::AID-DA2>3.0.CO;2-J9166648)
Fava M, Rush AJ, Alpert JE et al (2008) Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 165:342–351. (PMID: 10.1176/appi.ajp.2007.0611186818172020)
Katon W, Unützer J, Russo J (2010) Major depression: the importance of clinical characteristics and treatment response to prognosis. Depress Anxiety 27:19–26. (PMID: 10.1002/da.2061319798766)
Bandelow B, Michaelis S, Wedekind D (2017) Treatment of anxiety disorders. Dialogues Clin Neurosci 19:93–107. (PMID: 10.31887/DCNS.2017.19.2/bbandelow288679345573566)
Bandelow B, Sher L, Bunevicius R et al (2012) Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract 16:77–84. (PMID: 10.3109/13651501.2012.66711422540422)
Freeman MP, Fava M, Lake J et al (2010) Complementary and alternative medicine in major depressive disorder: the American Psychiatric Association Task Force report. J Clin Psychiatry 71:669–681. (PMID: 10.4088/JCP.10cs05959blu20573326)
Li F, Liu X, Zhang D (2016) Fish consumption and risk of depression: a meta-analysis. J Epidemiol Community Health 70:299–304. (PMID: 10.1136/jech-2015-20627826359502)
Kiecolt-Glaser JK, Belury MA, Andridge R et al (2011) Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial. Brain Behav Immun 25:1725–1734. (PMID: 10.1016/j.bbi.2011.07.229217841453191260)
Su KP, Tseng PT, Lin PY et al (2018) Association of use of omega-3 polyunsaturated fatty acids with changes in severity of anxiety symptoms: a systematic review and meta-analysis. JAMA Netw Open 1:e182327. (PMID: 10.1001/jamanetworkopen.2018.2327306461576324500)
Okereke OI, Vyas CM, Mischoulon D et al (2021) Effect of long-term supplementation with marine omega-3 fatty acids vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: a randomized clinical trial. JAMA 326:2385–2394. (PMID: 10.1001/jama.2021.21187349320798693224)
Amminger GP, Rice S, Davey CG et al (2024) The addition of Fish Oil to cognitive behavioral Case Management for Youth Depression: a Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial. Biol Psychiatry 95:426–433. (PMID: 10.1016/j.biopsych.2023.06.01537355004)
Yang R, Wang L, Jin K et al (2022) Omega-3 polyunsaturated fatty acids supplementation alleviate anxiety rather than depressive symptoms among first-diagnosed, drug-Naïve major depressive disorder patients: a randomized clinical trial. Front Nutr 9:876152. (PMID: 10.3389/fnut.2022.876152359034489315396)
Li N, Yang P, Tang M et al (2022) Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophrenia. Schizophrenia (Heidelb) 8:7. (PMID: 10.1038/s41537-022-00214-235217671)
Reddy RD, Keshavan MS, Yao JK (2004) Reduced red blood cell membrane essential polyunsaturated fatty acids in first episode schizophrenia at neuroleptic-naive baseline. Schizophr Bull 30:901–911. (PMID: 10.1093/oxfordjournals.schbul.a00714015957200)
Liu T, Wang L, Guo J et al (2023) Erythrocyte membrane fatty acid composition as a potential biomarker for depression. Int J Neuropsychopharmacol 26:385–395. (PMID: 10.1093/ijnp/pyad0213721725810289140)
McNamara RK, Jandacek R, Rider T et al (2011) Differential effects of antipsychotic medications on polyunsaturated fatty acid biosynthesis in rats: relationship with liver delta6-desaturase expression. Schizophr Res 129:57–65. (PMID: 10.1016/j.schres.2011.03.006214582373100388)
Brivio P, Audano M, Gallo MT et al (2023) Venlafaxine’s effect on resilience to stress is associated with a shift in the balance between glucose and fatty acid utilization. Neuropsychopharmacology: Official Publication Am Coll Neuropsychopharmacol 48:1475–1483. (PMID: 10.1038/s41386-023-01633-0)
Tkachev A, Stekolshchikova E, Bobrovskiy DM et al (2021) Long-term fluoxetine administration causes substantial lipidome alteration of the juvenile macaque brain. Int J Mol Sci 22.
He Y, Hogrefe CE, Grapov D et al (2014) Identifying individual differences of fluoxetine response in juvenile rhesus monkeys by metabolite profiling. Translational Psychiatry 4:e478. (PMID: 10.1038/tp.2014.116253691454259988)
Park SH, Ishino R (2013) Liver injury associated with antidepressants. Curr Drug Saf 8:207–223. (PMID: 10.2174/157488631130803001123914755)
Raeder MB, Fernø J, Glambek M et al (2006) Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells. Neurosci Lett 395:185–190. (PMID: 10.1016/j.neulet.2005.10.09616324787)
Moon ML, Joesting JJ, Lawson MA et al (2014) The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice. Metabolism 63:1131–1140. (PMID: 10.1016/j.metabol.2014.06.002250165204151238)
Nakajima S, Fukasawa K, Gotoh M et al (2020) Saturated fatty acid is a principal cause of anxiety-like behavior in diet-induced obese rats in relation to serum lysophosphatidyl choline level. Int J Obes (Lond) 44:727–738. (PMID: 10.1038/s41366-019-0468-z31636375)
Amminger GP, Nelson B, Markulev C et al (2020) The NEURAPRO biomarker analysis: long-chain omega-3 fatty acids improve 6-month and 12-month outcomes in youths at ultra-high risk for psychosis. Biol Psychiatry 87:243–252. (PMID: 10.1016/j.biopsych.2019.08.03031690495)
Berger ME, Smesny S, Kim SW et al (2017) Omega-6 to omega-3 polyunsaturated fatty acid ratio and subsequent mood disorders in young people with at-risk mental states: a 7-year longitudinal study. Translational Psychiatry 7:e1220. (PMID: 10.1038/tp.2017.190288501105611753)
Tang M, Floyd S, Cai H et al (2019) The status of ω-3 PUFAs influence chronic unpredicted mild stress-induced metabolic side effects in rats through INSIG/SREBP pathway. Food Funct 10:4649–4660. (PMID: 10.1039/C9FO00076C31292598)
Su KP, Yang HT, Chang JP et al (2018) Eicosapentaenoic and docosahexaenoic acids have different effects on peripheral phospholipase A2 gene expressions in acute depressed patients. Prog Neuro-psychopharmacol Biol Psychiatry 80:227–233. (PMID: 10.1016/j.pnpbp.2017.06.020)
Komprda T, Škultéty O, Křížková S et al (2015) Effect of dietary schizochytrium microalga oil and fish oil on plasma cholesterol level in rats. J Anim Physiol Anim Nutr (Berl) 99:308–316. (PMID: 10.1111/jpn.1222125040911)
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