Table Info

Table 4.

Impact of omega-3 PUFA supplementation on depression in youth: population, dosage, and efficacy insights

Study	Population	Intervention	Duration	Key findings	References
Pilot study on first-time DD/MADD	Children/adolescents (7–18 years)	Omega-3 PUFAs (1,000 mg EPA + 750 mg DHA) vs. n-6 PUFAs	Not specified	Significant reduction in depressive symptoms with omega-3 PUFAs; greater improvement in DD group vs. MADD group.	[171, 208]
Low-dose PUFA study in children	Children (6–12 years)	Omega-3 PUFAs (380–400 mg/day EPA + 180–200 mg/day DHA) vs. placebo	16 weeks	Greater improvement in depressive symptoms in the omega-3 PUFA group compared to placebo.	[171, 209, 210]
Dose-response study in adolescents	Adolescents with treatment-resistant MDD	High-dose (16.2 g) vs. low-dose (2.4 g) omega-3 PUFA supplementation	10 weeks	100% remission in high-dose group; 40% remission in low-dose group.	[211–213]
Larger trial in medication-free adolescents	Adolescents (12–19 years)	Omega-3 PUFA supplementation vs. placebo	Not specified	No significant differences: authors attributed findings to lack of baseline inflammatory markers.	[209, 211, 214, 215]

DD: depressive disorder; MADD: mixed anxiety and depressive disorder; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; PUFAs: polyunsaturated fatty acids; MDD: major depressive disorder

Declarations

Author contributions

RMG and MMN: Conceptualization, Writing—original draft, Writing—review & editing.

Conflicts of interest

The authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Smolińska K, Szopa A, Sobczyński J, Serefko A, Dobrowolski P. Nutritional Quality Implications: Exploring the Impact of a Fatty Acid-Rich Diet on Central Nervous System Development. Nutrients. 2024;16:1093. [DOI] [PubMed] [PMC]

Xiong Y, Li X, Liu J, Luo P, Zhang H, Zhou H, et al. Omega-3 PUFAs slow organ aging through promoting energy metabolism. Pharmacol Res. 2024;208:107384. [DOI] [PubMed]

Lee-Okada H, Xue C, Yokomizo T. Recent advances on the physiological and pathophysiological roles of polyunsaturated fatty acids and their biosynthetic pathway. Biochim Biophys Acta Mol Cell Biol Lipids. 2025;1870:159564. [DOI] [PubMed]

Worthmann A, Ridder J, Piel SYL, Evangelakos I, Musfeldt M, Voß H, et al. Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use. Nat Commun. 2024;15:45. [DOI] [PubMed] [PMC]

Balić A, Vlašić D, Žužul K, Marinović B, Mokos ZB. Omega-3 Versus Omega-6 Polyunsaturated Fatty Acids in the Prevention and Treatment of Inflammatory Skin Diseases. Int J Mol Sci. 2020;21:741. [DOI] [PubMed] [PMC]

Mariamenatu AH, Abdu EM. Overconsumption of Omega-6 Polyunsaturated Fatty Acids (PUFAs) versus Deficiency of Omega-3 PUFAs in Modern-Day Diets: The Disturbing Factor for Their “Balanced Antagonistic Metabolic Functions” in the Human Body. J Lipids. 2021;2021:8848161. [DOI] [PubMed] [PMC]

Mustonen A, Nieminen P. Dihomo- γ-Linolenic Acid (20:3n-6)-Metabolism, Derivatives, and Potential Significance in Chronic Inflammation. Int J Mol Sci. 2023;24:2116. [DOI] [PubMed] [PMC]

Baker EJ, Miles EA, Burdge GC, Yaqoob P, Calder PC. Metabolism and functional effects of plant-derived omega-3 fatty acids in humans. Prog Lipid Res. 2016;64:30–56. [DOI] [PubMed]

Banaszak M, Dobrzyńska M, Kawka A, Górna I, Woźniak D, Przysławski J, et al. Role of Omega-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic (DHA) as modulatory and anti-inflammatory agents in noncommunicable diet-related diseases - Reports from the last 10 years. Clin Nutr ESPEN. 2024;63:240–58. [DOI] [PubMed]

10.

Rao AS, Nair A, Nivetha K, Ayesha B, Hardi K, Divya V, et al. Impacts of Omega-3 Fatty Acids, Natural Elixirs for Neuronal Health, on Brain Development and Functions. Methods Mol Biol. 2024;2761:209–29. [DOI] [PubMed]

11.

Drouillet P, Forhan A, Lauzon-Guillain BD, Thiébaugeorges O, Goua V, Magnin G, et al. Maternal fatty acid intake and fetal growth: evidence for an association in overweight women. The ‘EDEN mother-child’ cohort (study of pre- and early postnatal determinants of the child’s development and health). Br J Nutr. 2009;101:583–91. [DOI] [PubMed] [PMC]

12.

Duttaroy AK, Basak S. Maternal Fatty Acid Metabolism in Pregnancy and Its Consequences in the Feto-Placental Development. Front Physiol. 2022;12:787848. [DOI] [PubMed] [PMC]

13.

Lauritzen L, Brambilla P, Mazzocchi A, Harsløf LBS, Ciappolino V, Agostoni C. DHA Effects in Brain Development and Function. Nutrients. 2016;8:6. [DOI] [PubMed] [PMC]

14.

Echeverría F, Valenzuela R, Hernandez-Rodas MC, Valenzuela A. Docosahexaenoic acid (DHA), a fundamental fatty acid for the brain: New dietary sources. Prostaglandins Leukot Essent Fatty Acids. 2017;124:1–10. [DOI] [PubMed]

15.

Likhar A, Patil MS. Importance of Maternal Nutrition in the First 1,000 Days of Life and Its Effects on Child Development: A Narrative Review. Cureus. 2022;14:e30083. [DOI] [PubMed] [PMC]

16.

Beluska-Turkan K, Korczak R, Hartell B, Moskal K, Maukonen J, Alexander DE, et al. Nutritional Gaps and Supplementation in the First 1000 Days. Nutrients. 2019;11:2891. [DOI] [PubMed] [PMC]

17.

Nevins JEH, Donovan SM, Snetselaar L, Dewey KG, Novotny R, Stang J, et al. Omega-3 Fatty Acid Dietary Supplements Consumed During Pregnancy and Lactation and Child Neurodevelopment: A Systematic Review. J Nutr. 2021;151:3483–94. [DOI] [PubMed] [PMC]

18.

Carlson SE, Colombo J. DHA and Cognitive Development. J Nutr. 2021;151:3265–6. [DOI] [PubMed] [PMC]

19.

Coletta JM, Bell SJ, Roman AS. Omega-3 Fatty acids and pregnancy. Rev Obstet Gynecol. 2010;3:163–71. [PubMed] [PMC]

20.

Pottala JV, Garg S, Cohen BE, Whooley MA, Harris WS. Blood eicosapentaenoic and docosahexaenoic acids predict all-cause mortality in patients with stable coronary heart disease: the Heart and Soul study. Circ Cardiovasc Qual Outcomes. 2010;3:406–12. [DOI] [PubMed] [PMC]

21.

Wen J, Satyanarayanan SK, Li A, Yan L, Zhao Z, Yuan Q, et al. Unraveling the impact of Omega-3 polyunsaturated fatty acids on blood-brain barrier (BBB) integrity and glymphatic function. Brain Behav Immun. 2024;115:335–55. [DOI] [PubMed]

22.

Schacky Cv. Omega-3 Fatty Acids in Pregnancy-The Case for a Target Omega-3 Index. Nutrients. 2020;12:898. [DOI] [PubMed] [PMC]

23.

Middleton P, Gomersall JC, Gould JF, Shepherd E, Olsen SF, Makrides M. Omega-3 fatty acid addition during pregnancy. Cochrane Database Syst Rev. 2018;11:CD003402. [DOI] [PubMed] [PMC]

24.

Wang T, Zhang X, Zhou N, Shen Y, Li B, Chen BE, et al. Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2023;12:e029512. [DOI] [PubMed] [PMC]

25.

Lane K, Derbyshire E, Li W, Brennan C. Bioavailability and potential uses of vegetarian sources of omega-3 fatty acids: a review of the literature. Crit Rev Food Sci Nutr. 2014;54:572–9. [DOI] [PubMed]

26.

Köhler A, Heinrich J, von Schacky C. Bioavailability of Dietary Omega-3 Fatty Acids Added to a Variety of Sausages in Healthy Individuals. Nutrients. 2017;9:629. [DOI] [PubMed] [PMC]

27.

Maki KC, Dicklin MR. Strategies to improve bioavailability of omega-3 fatty acids from ethyl ester concentrates. Curr Opin Clin Nutr Metab Care. 2019;22:116–23. [DOI] [PubMed]

28.

Stark KD, Van Elswyk ME, Higgins MR, Weatherford CA, Salem N Jr. Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog Lipid Res. 2016;63:132–52. [DOI] [PubMed]

29.

Harris WS. The omega-3 index: clinical utility for therapeutic intervention. Curr Cardiol Rep. 2010;12:503–8. [DOI] [PubMed]

30.

Medoro A, Buonsenso A, Centorbi M, Calcagno G, Scapagnini G, Fiorilli G, et al. Omega-3 Index as a Sport Biomarker: Implications for Cardiovascular Health, Injury Prevention, and Athletic Performance. J Funct Morphol Kinesiol. 2024;9:91. [DOI] [PubMed] [PMC]

31.

Basak S, Mallick R, Banerjee A, Pathak S, Duttaroy AK. Maternal Supply of Both Arachidonic and Docosahexaenoic Acids Is Required for Optimal Neurodevelopment. Nutrients. 2021;13:2061. [DOI] [PubMed] [PMC]

32.

Duttaroy AK, Basak S. Maternal dietary fatty acids and their roles in human placental development. Prostaglandins Leukot Essent Fatty Acids. 2020;155:102080. [DOI] [PubMed]

33.

Basak S, Mallick R, Duttaroy AK. Maternal Docosahexaenoic Acid Status during Pregnancy and Its Impact on Infant Neurodevelopment. Nutrients. 2020;12:3615. [DOI] [PubMed] [PMC]

34.

Nikolajeva K, Aizbalte O, Rezgale R, Cauce V, Zacs D, Meija L. The Intake of Omega-3 Fatty Acids, the Omega-3 Index in Pregnant Women, and Their Correlations with Gestational Length and Newborn Birth Weight. Nutrients. 2024;16:2150. [DOI] [PubMed] [PMC]

35.

Juber BA, Jackson KH, Johnson KB, Harris WS, Baack ML. Breast milk DHA levels may increase after informing women: a community-based cohort study from South Dakota USA. Int Breastfeed J. 2017;12:7. [DOI] [PubMed] [PMC]

36.

Saunders AV, Davis BC, Garg ML. Omega-3 polyunsaturated fatty acids and vegetarian diets. Med J Aust. 2013;199:S22–6. [DOI] [PubMed]

37.

Łuszczki E, Boakye F, Zielińska M, Dereń K, Bartosiewicz A, Oleksy Ł, et al. Vegan diet: nutritional components, implementation, and effects on adults’ health. Front Nutr. 2023;10:1294497. [DOI] [PubMed] [PMC]

38.

von Schacky C. Importance of EPA and DHA Blood Levels in Brain Structure and Function. Nutrients. 2021;13:1074. [DOI] [PubMed] [PMC]

39.

Lanier K, Wisseman B, Strom C, Johnston CA, Isler C, DeVente J, et al. Self-Reported Intake and Circulating EPA and DHA Concentrations in US Pregnant Women. Nutrients. 2023;15:1753. [DOI] [PubMed] [PMC]

40.

Weiser MJ, Butt CM, Mohajeri MH. Docosahexaenoic Acid and Cognition throughout the Lifespan. Nutrients. 2016;8:99. [DOI] [PubMed] [PMC]

41.

Brenna JT, Carlson SE. Docosahexaenoic acid and human brain development: evidence that a dietary supply is needed for optimal development. J Hum Evol. 2014;77:99–106. [DOI] [PubMed]

42.

Yelland LN, Gajewski BJ, Colombo J, Gibson RA, Makrides M, Carlson SE. Predicting the effect of maternal docosahexaenoic acid (DHA) supplementation to reduce early preterm birth in Australia and the United States using results of within country randomized controlled trials. Prostaglandins Leukot Essent Fatty Acids. 2016;112:44–9. [DOI] [PubMed] [PMC]

43.

Cetin I, Carlson SE, Burden C, da Fonseca EB, di Renzo GC, Hadjipanayis A, et al. Omega-3 fatty acid supply in pregnancy for risk reduction of preterm and early preterm birth. Am J Obstet Gynecol MFM. 2024;6:101251. [DOI] [PubMed]

44.

Best KP, Gibson RA, Makrides M. ISSFAL statement number 7 - Omega-3 fatty acids during pregnancy to reduce preterm birth. Prostaglandins Leukot Essent Fatty Acids. 2022;186:102495. [DOI] [PubMed]

45.

Carlson SE. Docosahexaenoic acid supplementation in pregnancy and lactation. Am J Clin Nutr. 2009;89:678S–84S. [DOI] [PubMed] [PMC]

46.

Braarud HC, Markhus MW, Skotheim S, Stormark KM, Frøyland L, Graff IE, et al. Maternal DHA Status during Pregnancy Has a Positive Impact on Infant Problem Solving: A Norwegian Prospective Observation Study. Nutrients. 2018;10:529. [DOI] [PubMed] [PMC]

47.

Bilgundi K, Viswanatha GL, Purushottam KM, John J, Kamath AP, Kishore A, et al. Docosahexaenoic Acid and Pregnancy: A Systematic Review and Meta-Analysis of the Association with Improved Maternal and Fetal Health. Nutr Res. 2024;128:82–93. [DOI] [PubMed]

48.

Makrides M, Gibson RA, McPhee AJ, Yelland L, Quinlivan J, Ryan P, et al. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. JAMA. 2010;304:1675–83. [DOI] [PubMed]

49.

Hadders-Algra M. Prenatal and early postnatal supplementation with long-chain polyunsaturated fatty acids: neurodevelopmental considerations. Am J Clin Nutr. 2011;94:1874S–9S. [DOI] [PubMed]

50.

Shahabi B, Hernández-Martínez C, Voltas N, Canals J, Arija V. The Maternal Omega-3 Long-Chain Polyunsaturated Fatty Acid Concentration in Early Pregnancy and Infant Neurodevelopment: The ECLIPSES Study. Nutrients. 2024;16:687. [DOI] [PubMed] [PMC]

51.

Carlson SE, Gajewski BJ, Valentine CJ, Kerling EH, Weiner CP, Cackovic M, et al. Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial. EClinicalMedicine. 2021;36:100905. [DOI] [PubMed] [PMC]

52.

Carlson SE, Gajewski BJ, Valentine CJ, Rogers LK, Weiner CP, DeFranco EA, et al. Assessment of DHA on reducing early preterm birth: the ADORE randomized controlled trial protocol. BMC Pregnancy Childbirth. 2017;17:62. [DOI] [PubMed] [PMC]

53.

Khandelwal S, Kondal D, Chaudhry M, Patil K, Swamy MK, Pujeri G, et al. Prenatal Maternal Docosahexaenoic Acid (DHA) Supplementation and Newborn Anthropometry in India: Findings from DHANI. Nutrients. 2021;13:730. [DOI] [PubMed] [PMC]

54.

Jiang Y, Chen Y, Wei L, Zhang H, Zhang J, Zhou X, et al. DHA supplementation and pregnancy complications. J Transl Med. 2023;21:394. [DOI] [PubMed] [PMC]

55.

Bozzatello P, Brignolo E, Grandi ED, Bellino S. Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data. J Clin Med. 2016;5:67. [DOI] [PubMed] [PMC]

56.

Skulas-Ray AC, Wilson PWF, Harris WS, Brinton EA, Kris-Etherton PM, Richter CK, et al.; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association. Circulation. 2019;140:e673–91. [DOI] [PubMed]

57.

Carretero-Krug A, Montero-Bravo A, Morais-Moreno C, Puga AM, Samaniego-Vaesken ML, Partearroyo T, et al. Nutritional Status of Breastfeeding Mothers and Impact of Diet and Dietary Supplementation: A Narrative Review. Nutrients. 2024;16:301. [DOI] [PubMed] [PMC]

58.

Agostoni C, Guz-Mark A, Marderfeld L, Milani GP, Silano M, Shamir R. The Long-Term Effects of Dietary Nutrient Intakes during the First 2 Years of Life in Healthy Infants from Developed Countries: An Umbrella Review. Adv Nutr. 2019;10:489–501. [DOI] [PubMed] [PMC]

59.

Dempsey M, Rockwell MS, Wentz LM. The influence of dietary and supplemental omega-3 fatty acids on the omega-3 index: A scoping review. Front Nutr. 2023;10:1072653. [DOI] [PubMed] [PMC]

60.

Amza M, Hamoud BH, Sima R, Dinu M, Gorecki G, Popescu M, et al. Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA)-Should They Be Mandatory Supplements in Pregnancy? Biomedicines. 2024;12:1471. [DOI] [PubMed] [PMC]

61.

Stonehouse W, Conlon CA, Podd J, Hill SR, Minihane AM, Haskell C, et al. DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial. Am J Clin Nutr. 2013;97:1134–43. [DOI] [PubMed]

62.

Colombo J, Gustafson KM, Gajewski BJ, Shaddy DJ, Kerling EH, Thodosoff JM, et al. Prenatal DHA supplementation and infant attention. Pediatr Res. 2016;80:656–62. [DOI] [PubMed] [PMC]

63.

Gould JF, Anderson PJ, Yelland LN, Gibson RA, Makrides M. The Influence of Prenatal DHA Supplementation on Individual Domains of Behavioral Functioning in School-Aged Children: Follow-Up of a Randomized Controlled Trial. Nutrients. 2021;13:2996. [DOI] [PubMed] [PMC]

64.

Wu A, Ying Z, Gomez-Pinilla F. Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience. 2008;155:751–9. [DOI] [PubMed] [PMC]

65.

Sharma S, Zhuang Y, Gomez-Pinilla F. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour. Sci Rep. 2012;2:431. [DOI] [PubMed] [PMC]

66.

Mallick R, Basak S, Duttaroy AK. Docosahexaenoic acid,22:6n-3: Its roles in the structure and function of the brain. Int J Dev Neurosci. 2019;79:21–31. [DOI] [PubMed]

67.

Sherzai D, Moness R, Sherzai S, Sherzai A. A Systematic Review of Omega-3 Fatty Acid Consumption and Cognitive Outcomes in Neurodevelopment. Am J Lifestyle Med. 2022;17:649–85. [DOI] [PubMed] [PMC]

68.

Chang JP. Personalised medicine in child and Adolescent Psychiatry: Focus on omega-3 polyunsaturated fatty acids and ADHD. Brain Behav Immun Health. 2021;16:100310. [DOI] [PubMed] [PMC]

69.

Gow RV, Hibbeln JR. Omega-3 fatty acid and nutrient deficits in adverse neurodevelopment and childhood behaviors. Child Adolesc Psychiatr Clin N Am. 2014;23:555–90. [DOI] [PubMed] [PMC]

70.

Peet M, Stokes C. Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs. 2005;65:1051–9. [DOI] [PubMed]

71.

Kim H, Huang BX, Spector AA. Molecular and Signaling Mechanisms for Docosahexaenoic Acid-Derived Neurodevelopment and Neuroprotection. Int J Mol Sci. 2022;23:4635. [DOI] [PubMed] [PMC]

72.

Prado EL, Dewey KG. Nutrition and brain development in early life. Nutr Rev. 2014;72:267–84. [DOI] [PubMed]

73.

Martinat M, Rossitto M, Miceli MD, Layé S. Perinatal Dietary Polyunsaturated Fatty Acids in Brain Development, Role in Neurodevelopmental Disorders. Nutrients. 2021;13:1185. [DOI] [PubMed] [PMC]

74.

Hu R, Xu J, Hua Y, Li Y, Li J. Could early life DHA supplementation benefit neurodevelopment? A systematic review and meta-analysis. Front Neurol. 2024;15:1295788. [DOI] [PubMed] [PMC]

75.

Crawford MA, Hassam AG, Williams G. Essential fatty acids and fetal brain growth. Lancet. 1976;1:452–3. [DOI] [PubMed]

76.

Luxwolda MF, Kuipers RS, Sango WS, Kwesigabo G, Dijck-Brouwer DAJ, Muskiet FAJ. A maternal erythrocyte DHA content of approximately 6 g% is the DHA status at which intrauterine DHA biomagnifications turns into bioattenuation and postnatal infant DHA equilibrium is reached. Eur J Nutr. 2012;51:665–75. [DOI] [PubMed] [PMC]

77.

Kuipers RS, Luxwolda MF, Sango WS, Kwesigabo G, Dijck-Brouwer DAJ, Muskiet FAJ. Maternal DHA equilibrium during pregnancy and lactation is reached at an erythrocyte DHA content of 8 g/100 g fatty acids. J Nutr. 2011;141:418–27. [DOI] [PubMed]

78.

Greenberg JA, Bell SJ, Ausdal WV. Omega-3 Fatty Acid supplementation during pregnancy. Rev Obstet Gynecol. 2008;1:162–9. [PubMed] [PMC]

79.

Gustafson KM, Christifano DN, Hoyer D, Schmidt A, Carlson SE, Colombo J, et al. Prenatal docosahexaenoic acid effect on maternal-infant DHA-equilibrium and fetal neurodevelopment: a randomized clinical trial. Pediatr Res. 2022;92:255–64. [DOI] [PubMed] [PMC]

80.

Vollet K, Ghassabian A, Sundaram R, Chahal N, Yeung EH. Prenatal fish oil supplementation and early childhood development in the Upstate KIDS Study. J Dev Orig Health Dis. 2017;8:465–73. [DOI] [PubMed] [PMC]

81.

Carlson SE, Colombo J, Gajewski BJ, Gustafson KM, Mundy D, Yeast J, et al. DHA supplementation and pregnancy outcomes. Am J Clin Nutr. 2013;97:808–15. [DOI] [PubMed] [PMC]

82.

Rogers LK, Valentine CJ, Keim SA. DHA supplementation: current implications in pregnancy and childhood. Pharmacol Res. 2013;70:13–9. [DOI] [PubMed] [PMC]

83.

Meldrum SJ, D’Vaz N, Simmer K, Dunstan JA, Hird K, Prescott SL. Effects of high-dose fish oil supplementation during early infancy on neurodevelopment and language: a randomised controlled trial. Br J Nutr. 2012;108:1443–54. [DOI] [PubMed]

84.

Zhang Z, Fulgoni VL, Kris-Etherton PM, Mitmesser SH. Dietary Intakes of EPA and DHA Omega-3 Fatty Acids among US Childbearing-Age and Pregnant Women: An Analysis of NHANES 2001-2014. Nutrients. 2018;10:416. [DOI] [PubMed] [PMC]

85.

Healy-Stoffel M, Levant B. N-3 (Omega-3) Fatty Acids: Effects on Brain Dopamine Systems and Potential Role in the Etiology and Treatment of Neuropsychiatric Disorders. CNS Neurol Disord Drug Targets. 2018;17:216–32. [DOI] [PubMed] [PMC]

86.

Cao D, Kevala K, Kim J, Moon H, Jun SB, Lovinger D, et al. Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. J Neurochem. 2009;111:510–21. [DOI] [PubMed] [PMC]

87.

Dyall SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci. 2015;7:52. [DOI] [PubMed] [PMC]

88.

DiNicolantonio JJ, O’Keefe JH. The Importance of Marine Omega-3s for Brain Development and the Prevention and Treatment of Behavior, Mood, and Other Brain Disorders. Nutrients. 2020;12:2333. [DOI] [PubMed] [PMC]

89.

Cutuli D. Functional and Structural Benefits Induced by Omega-3 Polyunsaturated Fatty Acids During Aging. Curr Neuropharmacol. 2017;15:534–42. [DOI] [PubMed] [PMC]

90.

Vinding RK, Sevelsted A, Horner D, Vahman N, Lauritzen L, Hagen CP, et al. Fish oil supplementation during pregnancy, anthropometrics, and metabolic health at age ten: A randomized clinical trial. Am J Clin Nutr. 2024;119:960–8. [DOI] [PubMed]

91.

Campoy C, Escolano-Margarit MV, Anjos T, Szajewska H, Uauy R. Omega 3 fatty acids on child growth, visual acuity and neurodevelopment. Br J Nutr. 2012;107:S85–106. [DOI] [PubMed]

92.

Checa-Ros A, D’Marco L. Role of Omega-3 Fatty Acids as Non-Photic Zeitgebers and Circadian Clock Synchronizers. Int J Mol Sci. 2022;23:12162. [DOI] [PubMed] [PMC]

93.

Sinclair AJ. Docosahexaenoic acid and the brain- what is its role? Asia Pac J Clin Nutr. 2019;28:675–88. [DOI] [PubMed]

94.

Dai Y, Liu J. Omega-3 long-chain polyunsaturated fatty acid and sleep: a systematic review and meta-analysis of randomized controlled trials and longitudinal studies. Nutr Rev. 2021;79:847–68. [DOI] [PubMed] [PMC]

95.

Li L, Wu J, Chen Z, Weir NL, Tsai MY, Albert P, et al. Plasma phospholipid polyunsaturated fatty acids composition in early pregnancy and fetal growth trajectories throughout pregnancy: Findings from the US fetal growth studies-singletons cohort. EBioMedicine. 2022;82:104180. [DOI] [PubMed] [PMC]

96.

Zou R, Marroun HE, Voortman T, Hillegers M, White T, Tiemeier H. Maternal polyunsaturated fatty acids during pregnancy and offspring brain development in childhood. Am J Clin Nutr. 2021;114:124–33. [DOI] [PubMed]

97.

Brett KE, Ferraro ZM, Yockell-Lelievre J, Gruslin A, Adamo KB. Maternal-fetal nutrient transport in pregnancy pathologies: the role of the placenta. Int J Mol Sci. 2014;15:16153–85. [DOI] [PubMed] [PMC]

98.

Heath RJ, Klevebro S, Wood TR. Maternal and Neonatal Polyunsaturated Fatty Acid Intake and Risk of Neurodevelopmental Impairment in Premature Infants. Int J Mol Sci. 2022;23:700. [DOI] [PubMed] [PMC]

99.

Lewin GA, Schachter HM, Yuen D, Merchant P, Mamaladze V, Tsertsvadze A. Effects of omega-3 fatty acids on child and maternal health. Evid Rep Technol Assess (Summ). 2005:1–11. [PubMed] [PMC]

100.

Jones KL, Will MJ, Hecht PM, Parker CL, Beversdorf DQ. Maternal diet rich in omega-6 polyunsaturated fatty acids during gestation and lactation produces autistic-like sociability deficits in adult offspring. Behav Brain Res. 2013;238:193–9. [DOI] [PubMed]

101.

Jiang Y, Dang W, Nie H, Kong X, Jiang Z, Guo J. Omega-3 polyunsaturated fatty acids and/or vitamin D in autism spectrum disorders: a systematic review. Front Psychiatry. 2023;14:1238973. [DOI] [PubMed] [PMC]

102.

Borasio F, Cosmi VD, D’Oria V, Scaglioni S, Syren ME, Turolo S, et al. Associations between Dietary Intake, Blood Levels of Omega-3 and Omega-6 Fatty Acids and Reading Abilities in Children. Biomolecules. 2023;13:368. [DOI] [PubMed] [PMC]

103.

Pancheva RZ, Nikolova S, Serbezova A, Zaykova K, Zhelyazkova D, Dimitrov L. Evidence or no evidence for essential fatty acids in the treatment of autism spectrum disorders? Front Nutr. 2023;10:1251083. [DOI] [PubMed] [PMC]

104.

Sambra V, Echeverria F, Valenzuela A, Chouinard-Watkins R, Valenzuela R. Docosahexaenoic and Arachidonic Acids as Neuroprotective Nutrients throughout the Life Cycle. Nutrients. 2021;13:986. [DOI] [PubMed] [PMC]

105.

McNamara RK, Vannest JJ, Valentine CJ. Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation: Mechanisms and implications for psychopathology. World J Psychiatry. 2015;5:15–34. [DOI] [PubMed] [PMC]

106.

Cortés-Albornoz MC, García-Guáqueta DP, Velez-van-Meerbeke A, Talero-Gutiérrez C. Maternal Nutrition and Neurodevelopment: A Scoping Review. Nutrients. 2021;13:3530. [DOI] [PubMed] [PMC]

107.

Cinquina V, Keimpema E, Pollak DD, Harkany T. Adverse effects of gestational ω-3 and ω-6 polyunsaturated fatty acid imbalance on the programming of fetal brain development. J Neuroendocrinol. 2023;35:e13320. [DOI] [PubMed] [PMC]

108.

Bazan NG, Molina MF, Gordon WC. Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer’s, and other neurodegenerative diseases. Annu Rev Nutr. 2011;31:321–51. [DOI] [PubMed] [PMC]

109.

Wu A, Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma. 2004;21:1457–67. [DOI] [PubMed]

110.

Sun GY, Simonyi A, Fritsche KL, Chuang DY, Hannink M, Gu Z, et al. Docosahexaenoic acid (DHA): An essential nutrient and a nutraceutical for brain health and diseases. Prostaglandins Leukot Essent Fatty Acids. 2018;136:3–13. [DOI] [PubMed] [PMC]

111.

Fan C, Fu H, Dong H, Lu Y, Lu Y, Qi K. Maternal n-3 polyunsaturated fatty acid deprivation during pregnancy and lactation affects neurogenesis and apoptosis in adult offspring: associated with DNA methylation of brain-derived neurotrophic factor transcripts. Nutr Res. 2016;36:1013–21. [DOI] [PubMed]

112.

Srinivas V, Varma S, Kona SR, Ibrahim A, Duttaroy AK, Basak S. Dietary omega-3 fatty acid deficiency from pre-pregnancy to lactation affects expression of genes involved in hippocampal neurogenesis of the offspring. Prostaglandins Leukot Essent Fatty Acids. 2023;191:102566. [DOI] [PubMed]

113.

Bradbury J. Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain. Nutrients. 2011;3:529–54. [DOI] [PubMed] [PMC]

114.

Petermann AB, Reyna-Jeldes M, Ortega L, Coddou C, Yévenes GE. Roles of the Unsaturated Fatty Acid Docosahexaenoic Acid in the Central Nervous System: Molecular and Cellular Insights. Int J Mol Sci. 2022;23:5390. [DOI] [PubMed] [PMC]

115.

Chianese R, Coccurello R, Viggiano A, Scafuro M, Fiore M, Coppola G, et al. Impact of Dietary Fats on Brain Functions. Curr Neuropharmacol. 2018;16:1059–85. [DOI] [PubMed] [PMC]

116.

Lee JM, Lee H, Kang S, Park WJ. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances. Nutrients. 2016;8:23. [DOI] [PubMed] [PMC]

117.

Tosi F, Sartori F, Guarini P, Olivieri O, Martinelli N. Delta-5 and delta-6 desaturases: crucial enzymes in polyunsaturated fatty acid-related pathways with pleiotropic influences in health and disease. Adv Exp Med Biol. 2014;824:61–81. [DOI] [PubMed]

118.

Sarparast M, Dattmore D, Alan J, Lee KSS. Cytochrome P450 Metabolism of Polyunsaturated Fatty Acids and Neurodegeneration. Nutrients. 2020;12:3523. [DOI] [PubMed] [PMC]

119.

Hajeyah AA, Griffiths WJ, Wang Y, Finch AJ, O’Donnell VB. The Biosynthesis of Enzymatically Oxidized Lipids. Front Endocrinol (Lausanne). 2020;11:591819. [DOI] [PubMed] [PMC]

120.

Harwood JL. Polyunsaturated Fatty Acids: Conversion to Lipid Mediators, Roles in Inflammatory Diseases and Dietary Sources. Int J Mol Sci. 2023;24:8838. [DOI] [PubMed] [PMC]

121.

National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Food and Nutrition Board. Nutrition During Pregnancy and Lactation: Exploring New Evidence: Proceedings of a Workshop. Washington: National Academies Press; 2020. [DOI] [PubMed]

122.

Miketinas D, Luo H, Firth JA, Bailey A, Bender T, Gross G, et al. Macronutrient and Micronutrient Intake Among US Women Aged 20 to 44 Years. JAMA Netw Open. 2024;7:e2438460. [DOI] [PubMed] [PMC]

123.

Bäck M, Xhaard C, Rouget R, Thuillier Q, Plunde O, Larsson SC, et al. Fatty acid desaturase genetic variations and dietary omega-3 fatty acid intake associate with arterial stiffness. Eur Heart J Open. 2022;2:oeac016. [DOI] [PubMed] [PMC]

124.

Chilton FH, Manichaikul A, Yang C, O’Connor TD, Johnstone LM, Blomquist S, et al. Interpreting Clinical Trials With Omega-3 Supplements in the Context of Ancestry and FADS Genetic Variation. Front Nutr. 2022;8:808054. [DOI] [PubMed] [PMC]

125.

Barabási DL, Schuhknecht GFP, Engert F. Functional neuronal circuits emerge in the absence of developmental activity. Nat Commun. 2024;15:364. [DOI] [PubMed] [PMC]

126.

Jiang X, Nardelli J. Cellular and molecular introduction to brain development. Neurobiol Dis. 2016;92:3–17. [DOI] [PubMed] [PMC]

127.

Colonna M, Butovsky O. Microglia Function in the Central Nervous System During Health and Neurodegeneration. Annu Rev Immunol. 2017;35:441–68. [DOI] [PubMed] [PMC]

128.

Gao C, Jiang J, Tan Y, Chen S. Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets. Signal Transduct Target Ther. 2023;8:359. [DOI] [PubMed] [PMC]

129.

Eltokhi A, Janmaat IE, Genedi M, Haarman BCM, Sommer IEC. Dysregulation of synaptic pruning as a possible link between intestinal microbiota dysbiosis and neuropsychiatric disorders. J Neurosci Res. 2020;98:1335–69. [DOI] [PubMed]

130.

Leyrolle Q, Decoeur F, Briere G, Amadieu C, Quadros ARAA, Voytyuk I, et al. Maternal dietary omega-3 deficiency worsens the deleterious effects of prenatal inflammation on the gut-brain axis in the offspring across lifetime. Neuropsychopharmacology. 2021;46:579–602. [DOI] [PubMed] [PMC]

131.

Madore C, Leyrolle Q, Morel L, Rossitto M, Greenhalgh AD, Delpech JC, et al. Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain. Nat Commun. 2020;11:6133. [DOI] [PubMed] [PMC]

132.

Konishi H, Kiyama H, Ueno M. Dual functions of microglia in the formation and refinement of neural circuits during development. Int J Dev Neurosci. 2019;77:18–25. [DOI] [PubMed]

133.

Nayak D, Roth TL, McGavern DB. Microglia development and function. Annu Rev Immunol. 2014;32:367–402. [DOI] [PubMed] [PMC]

134.

Wright B, King S, Suphioglu C. The Importance of Phosphoinositide 3-Kinase in Neuroinflammation. Int J Mol Sci. 2024;25:11638. [DOI] [PubMed] [PMC]

135.

Chu E, Mychasiuk R, Hibbs ML, Semple BD. Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation. J Neuroinflammation. 2021;18:276. [DOI] [PubMed] [PMC]

136.

Soteros BM, Sia GM. Complement and microglia dependent synapse elimination in brain development. WIREs Mech Dis. 2022;14:e1545. [DOI] [PubMed] [PMC]

137.

Cornell J, Salinas S, Huang H, Zhou M. Microglia regulation of synaptic plasticity and learning and memory. Neural Regen Res. 2022;17:705–16. [DOI] [PubMed] [PMC]

138.

Gomez-Arboledas A, Acharya MM, Tenner AJ. The Role of Complement in Synaptic Pruning and Neurodegeneration. Immunotargets Ther. 2021;10:373–86. [DOI] [PubMed] [PMC]

139.

Wang B, Wu L, Chen J, Dong L, Chen C, Wen Z, et al. Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets. Signal Transduct Target Ther. 2021;6:94. [DOI] [PubMed] [PMC]

140.

Benatzy Y, Palmer MA, Brüne B. Arachidonate 15-lipoxygenase type B: Regulation, function, and its role in pathophysiology. Front Pharmacol. 2022;13:1042420. [DOI] [PubMed] [PMC]

141.

Hajjar T, Meng GY, Rajion MA, Vidyadaran S, Othman F, Farjam AS, et al. Omega 3 polyunsaturated fatty acid improves spatial learning and hippocampal peroxisome proliferator activated receptors (PPARα and PPARγ) gene expression in rats. BMC Neurosci. 2012;13:109. [DOI] [PubMed] [PMC]

142.

Heras-Sandoval D, Pedraza-Chaverri J, Pérez-Rojas JM. Role of docosahexaenoic acid in the modulation of glial cells in Alzheimer’s disease. J Neuroinflammation. 2016;13:61. [DOI] [PubMed] [PMC]

143.

Casali BT, Reed-Geaghan EG. Microglial Function and Regulation during Development, Homeostasis and Alzheimer’s Disease. Cells. 2021;10:957. [DOI] [PubMed] [PMC]

144.

Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol. 2013;75:645–62. [DOI] [PubMed] [PMC]

145.

Loving BA, Bruce KD. Lipid and Lipoprotein Metabolism in Microglia. Front Physiol. 2020;11:393. [DOI] [PubMed] [PMC]

146.

Folick A, Koliwad SK, Valdearcos M. Microglial Lipid Biology in the Hypothalamic Regulation of Metabolic Homeostasis. Front Endocrinol (Lausanne). 2021;12:668396. [DOI] [PubMed] [PMC]

147.

Decoeur F, Picard K, St-Pierre M, Greenhalgh AD, Delpech J, Sere A, et al. N-3 PUFA Deficiency Affects the Ultrastructural Organization and Density of White Matter Microglia in the Developing Brain of Male Mice. Front Cell Neurosci. 2022;16:802411. [DOI] [PubMed] [PMC]

148.

Lim TK, Ruthazer ES. Microglial trogocytosis and the complement system regulate axonal pruning in vivo. Elife. 2021;10:e62167. [DOI] [PubMed] [PMC]

149.

Stephan AH, Barres BA, Stevens B. The complement system: an unexpected role in synaptic pruning during development and disease. Annu Rev Neurosci. 2012;35:369–89. [DOI] [PubMed]

150.

Zhong L, Sheng X, Wang W, Li Y, Zhuo R, Wang K, et al. TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration. Immunity. 2023;56:1794–808.e8. [DOI] [PubMed]

151.

Liu J, Wang Q, You Q, Li Z, Hu N, Wang Y, et al. Acute EPA-induced learning and memory impairment in mice is prevented by DHA. Nat Commun. 2020;11:5465. [DOI] [PubMed] [PMC]

152.

Labrousse VF, Nadjar A, Joffre C, Costes L, Aubert A, Grégoire S, et al. Short-term long chain omega3 diet protects from neuroinflammatory processes and memory impairment in aged mice. PLoS One. 2012;7:e36861. [DOI] [PubMed] [PMC]

153.

Latour A, Grintal B, Champeil-Potokar G, Hennebelle M, Lavialle M, Dutar P, et al. Omega-3 fatty acids deficiency aggravates glutamatergic synapse and astroglial aging in the rat hippocampal CA1. Aging Cell. 2013;12:76–84. [DOI] [PubMed]

154.

Dayananda KK, Ahmed S, Wang D, Polis B, Islam R, Kaffman A. Early life stress impairs synaptic pruning in the developing hippocampus. Brain Behav Immun. 2023;107:16–31. [DOI] [PubMed] [PMC]

155.

Agostoni C, Nobile M, Ciappolino V, Delvecchio G, Tesei A, Turolo S, et al. The Role of Omega-3 Fatty Acids in Developmental Psychopathology: A Systematic Review on Early Psychosis, Autism, and ADHD. Int J Mol Sci. 2017;18:2608. [DOI] [PubMed] [PMC]

156.

Delpech J, Thomazeau A, Madore C, Bosch-Bouju C, Larrieu T, Lacabanne C, et al. Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced Spatial Memory Impairment. Neuropsychopharmacology. 2015;40:2774–87. [DOI] [PubMed] [PMC]

157.

Tang M, Zhang M, Cai H, Li H, Jiang P, Dang R, et al. Maternal diet of polyunsaturated fatty acid altered the cell proliferation in the dentate gyrus of hippocampus and influenced glutamatergic and serotoninergic systems of neonatal female rats. Lipids Health Dis. 2016;15:71. [DOI] [PubMed] [PMC]

158.

Moreira JD, Knorr L, Ganzella M, Thomazi AP, de Souza CG, de Souza DG, et al. Omega-3 fatty acids deprivation affects ontogeny of glutamatergic synapses in rats: relevance for behavior alterations. Neurochem Int. 2010;56:753–9. [DOI] [PubMed]

159.

Frajerman A, Scoriels L, Kebir O, Chaumette B. Shared Biological Pathways between Antipsychotics and Omega-3 Fatty Acids: A Key Feature for Schizophrenia Preventive Treatment? Int J Mol Sci. 2021;22:6881. [DOI] [PubMed] [PMC]

160.

Tanaka K, Farooqui AA, Siddiqi NJ, Alhomida AS, Ong W. Effects of docosahexaenoic Acid on neurotransmission. Biomol Ther (Seoul). 2012;20:152–7. [DOI] [PubMed] [PMC]

161.

Rouch L, Giudici KV, Cantet C, Guyonnet S, Delrieu J, Legrand P, et al. Associations of erythrocyte omega-3 fatty acids with cognition, brain imaging and biomarkers in the Alzheimer’s disease neuroimaging initiative: cross-sectional and longitudinal retrospective analyses. Am J Clin Nutr. 2022;116:1492–506. [DOI] [PubMed] [PMC]

162.

Lehner A, Staub K, Aldakak L, Eppenberger P, Rühli F, Martin RD, et al. Impact of omega-3 fatty acid DHA and EPA supplementation in pregnant or breast-feeding women on cognitive performance of children: systematic review and meta-analysis. Nutr Rev. 2021;79:585–98. [DOI] [PubMed]

163.

Dobrian AD, Lieb DC, Cole BK, Taylor-Fishwick DA, Chakrabarti SK, Nadler JL. Functional and pathological roles of the 12- and 15-lipoxygenases. Prog Lipid Res. 2011;50:115–31. [DOI] [PubMed] [PMC]

164.

Fu Y, Wang Y, Gao H, Li D, Jiang R, Ge L, et al. Associations among Dietary Omega-3 Polyunsaturated Fatty Acids, the Gut Microbiota, and Intestinal Immunity. Mediators Inflamm. 2021;2021:8879227. [DOI] [PubMed] [PMC]

165.

Zhou L, Xiong J, Chai Y, Huang L, Tang Z, Zhang X, et al. Possible antidepressant mechanisms of omega-3 polyunsaturated fatty acids acting on the central nervous system. Front Psychiatry. 2022;13:933704. [DOI] [PubMed] [PMC]

166.

Serefko A, Jach ME, Pietraszuk M, Świąder M, Świąder K, Szopa A. Omega-3 Polyunsaturated Fatty Acids in Depression. Int J Mol Sci. 2024;25:8675. [DOI] [PubMed] [PMC]

167.

Mozurkewich EL, Clinton CM, Chilimigras JL, Hamilton SE, Allbaugh LJ, Berman DR, et al. The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial. Am J Obstet Gynecol. 2013;208:313.e1–9. [DOI] [PubMed] [PMC]

168.

Levant B. N-3 (omega-3) Fatty acids in postpartum depression: implications for prevention and treatment. Depress Res Treat. 2011;2011:467349. [DOI] [PubMed] [PMC]

169.

Labrousse VF, Leyrolle Q, Amadieu C, Aubert A, Sere A, Coutureau E, et al. Dietary omega-3 deficiency exacerbates inflammation and reveals spatial memory deficits in mice exposed to lipopolysaccharide during gestation. Brain Behav Immun. 2018;73:427–40. [DOI] [PubMed]

170.

Tang M, Zhang M, Wang L, Li H, Cai H, Dang R, et al. Maternal dietary of n-3 polyunsaturated fatty acids affects the neurogenesis and neurochemical in female rat at weaning. Prostaglandins Leukot Essent Fatty Acids. 2018;128:11–20. [DOI] [PubMed]

171.

Chang JP, Su KP. Nutritional Neuroscience as Mainstream of Psychiatry: The Evidence- Based Treatment Guidelines for Using Omega-3 Fatty Acids as a New Treatment for Psychiatric Disorders in Children and Adolescents. Clin Psychopharmacol Neurosci. 2020;18:469–83. [DOI] [PubMed] [PMC]

172.

Vecchione R, Vigna C, Whitman C, Kauffman EM, Braun JM, Chen A, et al. The Association Between Maternal Prenatal Fish Intake and Child Autism-Related Traits in the EARLI and HOME Studies. J Autism Dev Disord. 2021;51:487–500. [DOI] [PubMed] [PMC]

173.

Julvez J, Méndez M, Fernandez-Barres S, Romaguera D, Vioque J, Llop S, et al. Maternal Consumption of Seafood in Pregnancy and Child Neuropsychological Development: A Longitudinal Study Based on a Population With High Consumption Levels. Am J Epidemiol. 2016;183:169–82. [DOI] [PubMed]

174.

Sinclair AJ, Wang Y, Li D. What Is the Evidence for Dietary-Induced DHA Deficiency in Human Brains? Nutrients. 2022;15:161. [DOI] [PubMed] [PMC]

175.

Mullen S. Major depressive disorder in children and adolescents. Ment Health Clin. 2018;8:275–83. [DOI] [PubMed] [PMC]

176.

Dwyer JB, Bloch MH. Antidepressants for Pediatric Patients. Curr Psychiatr. 2019;18:26–42F. [PubMed] [PMC]

177.

Chaves RdCS, Aguiar OB, Moreno AB, Brunoni AR, Molina MDCB, Viana MC, et al. Consumption of Omega-3 and Maintenance and Incidence of Depressive Episodes: The ELSA-Brasil Study. Nutrients. 2022;14:3227. [DOI] [PubMed] [PMC]

178.

Larrieu T, Laye S. Food for Mood: Relevance of Nutritional Omega-3 Fatty Acids for Depression and Anxiety. Front Physiol. 2018;9:1047. [DOI] [PubMed] [PMC]

179.

Carney RM, Freedland KE, Stein PK, Steinmeyer BC, Harris WS, Rubin EH, et al. Effect of omega-3 fatty acids on heart rate variability in depressed patients with coronary heart disease. Psychosom Med. 2010;72:748–54. [DOI] [PubMed] [PMC]

180.

Grosso G, Galvano F, Marventano S, Malaguarnera M, Bucolo C, Drago F, et al. Omega-3 fatty acids and depression: scientific evidence and biological mechanisms. Oxid Med Cell Longev. 2014;2014:313570. [DOI] [PubMed] [PMC]

181.

Tribulova N, Bacova BS, Benova TE, Knezl V, Barancik M, Slezak J. Omega-3 Index and Anti-Arrhythmic Potential of Omega-3 PUFAs. Nutrients. 2017;9:1191. [DOI] [PubMed] [PMC]

182.

Troubat R, Barone P, Leman S, Desmidt T, Cressant A, Atanasova B, et al. Neuroinflammation and depression: A review. Eur J Neurosci. 2021;53:151–71. [DOI] [PubMed]

183.

Richardson B, MacPherson A, Bambico F. Neuroinflammation and neuroprogression in depression: Effects of alternative drug treatments. Brain Behav Immun Health. 2022;26:100554. [DOI] [PubMed] [PMC]

184.

Malau IA, Chang JP, Lin Y, Chang C, Chiu W, Su K. Omega-3 Fatty Acids and Neuroinflammation in Depression: Targeting Damage-Associated Molecular Patterns and Neural Biomarkers. Cells. 2024;13:1791. [DOI] [PubMed] [PMC]

185.

Li X, Bi X, Wang S, Zhang Z, Li F, Zhao AZ. Therapeutic Potential of ω-3 Polyunsaturated Fatty Acids in Human Autoimmune Diseases. Front Immunol. 2019;10:2241. [DOI] [PubMed] [PMC]

186.

Gutiérrez S, Svahn SL, Johansson ME. Effects of Omega-3 Fatty Acids on Immune Cells. Int J Mol Sci. 2019;20:5028. [DOI] [PubMed] [PMC]

187.

Calder PC. Omega-3 fatty acids and inflammatory processes. Nutrients. 2010;2:355–374. [DOI] [PubMed] [PMC]

188.

Joffre C, Rey C, Layé S. N-3 Polyunsaturated Fatty Acids and the Resolution of Neuroinflammation. Front Pharmacol. 2019;10:1022. [DOI] [PubMed] [PMC]

189.

Giacobbe J, Benoiton B, Zunszain P, Pariante CM, Borsini A. The Anti-Inflammatory Role of Omega-3 Polyunsaturated Fatty Acids Metabolites in Pre-Clinical Models of Psychiatric, Neurodegenerative, and Neurological Disorders. Front Psychiatry. 2020;11:122. [DOI] [PubMed] [PMC]

190.

Su K, Lai H, Yang H, Su W, Peng C, Chang JP, et al. Omega-3 fatty acids in the prevention of interferon-alpha-induced depression: results from a randomized, controlled trial. Biol Psychiatry. 2014;76:559–66. [DOI] [PubMed]

191.

Costantini L, Molinari R, Farinon B, Merendino N. Impact of Omega-3 Fatty Acids on the Gut Microbiota. Int J Mol Sci. 2017;18:2645. [DOI] [PubMed] [PMC]

192.

Berding K, Vlckova K, Marx W, Schellekens H, Stanton C, Clarke G, et al. Diet and the Microbiota-Gut-Brain Axis: Sowing the Seeds of Good Mental Health. Adv Nutr. 2021;12:1239–85. [DOI] [PubMed] [PMC]

193.

Marrone MC, Coccurello R. Dietary Fatty Acids and Microbiota-Brain Communication in Neuropsychiatric Diseases. Biomolecules. 2019;10:12. [DOI] [PubMed] [PMC]

194.

Borrego-Ruiz A, Borrego JJ. Human gut microbiome, diet, and mental disorders. Int Microbiol. 2025;28:1–15. [DOI] [PubMed] [PMC]

195.

Borrego-Ruiz A, Borrego JJ. Neurodevelopmental Disorders Associated with Gut Microbiome Dysbiosis in Children. Children (Basel). 2024;11:796. [DOI] [PubMed] [PMC]

196.

Bodur M, Yilmaz B, Agagunduz D, Ozogul Y. Immunomodulatory Effects of Omega-3 Fatty Acids: Mechanistic Insights and Health Implications. Mol Nutr Food Res. 2025;e202400752. [DOI] [PubMed]

197.

Chen X, Wu S, Chen C, Xie B, Fang Z, Hu W, et al. Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-induced inflammation by inhibiting the HMGB1/TLR4/NF-κB pathway following experimental traumatic brain injury. J Neuroinflammation. 2017;14:143. [DOI] [PubMed] [PMC]

198.

Liu L, Wang H, Chen X, Zhang Y, Zhang H, Xie P. Gut microbiota and its metabolites in depression: from pathogenesis to treatment. EBioMedicine. 2023;90:104527. [DOI] [PubMed] [PMC]

199.

Zheng P, Zeng B, Zhou C, Liu M, Fang Z, Xu X, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol Psychiatry. 2016;21:786–96. [DOI] [PubMed]

200.

Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. [DOI] [PubMed] [PMC]

201.

Vecsey CG, Hawk JD, Lattal KM, Stein JM, Fabian SA, Attner MA, et al. Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation. J Neurosci. 2007;27:6128–40. [DOI] [PubMed] [PMC]

202.

Patrick RP, Ames BN. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. FASEB J. 2015;29:2207–22. [DOI] [PubMed]

203.

Tomczyk M, Bidzan-Wiącek M, Kortas JA, Kochanowicz M, Jost Z, Fisk HL, et al. Omega-3 fatty acid supplementation affects tryptophan metabolism during a 12-week endurance training in amateur runners: a randomized controlled trial. Sci Rep. 2024;14:4102. [DOI] [PubMed] [PMC]

204.

Ney L, Wipplinger M, Grossmann M, Engert N, Wegner VD, Mosig AS. Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections. Open Biol. 2023;13:230014. [DOI] [PubMed] [PMC]

205.

Ziaei S, Mohammadi S, Hasani M, Morvaridi M, Belančić A, Daneshzad E, et al. A systematic review and meta-analysis of the omega-3 fatty acids effects on brain-derived neurotrophic factor (BDNF). Nutr Neurosci. 2024;27:715–25. [DOI] [PubMed]

206.

Vyas CM, Mischoulon D, Chang G, 3rd CFR, Cook NR, Weinberg A, et al. Relation of serum BDNF to major depression and exploration of mechanistic roles of serum BDNF in a study of vitamin D3 and omega-3 supplements for late-life depression prevention. J Psychiatr Res. 2023;163:357–64. [DOI] [PubMed] [PMC]

207.

Guo C, Liu Y, Fang M, Li Y, Li W, Mahaman YAR, et al. ω-3PUFAs Improve Cognitive Impairments Through Ser133 Phosphorylation of CREB Upregulating BDNF/TrkB Signal in Schizophrenia. Neurotherapeutics. 2020;17:1271–86. [DOI] [PubMed] [PMC]

208.

Trebatická J, Hradečná Z, Böhmer F, Vaváková M, Waczulíková I, Garaiova I, et al. Emulsified omega-3 fatty-acids modulate the symptoms of depressive disorder in children and adolescents: a pilot study. Child Adolesc Psychiatry Ment Health. 2017;11:30. [DOI] [PubMed] [PMC]

209.

Campisi SC, Zasowski C, Bradley-Ridout G, Schumacher A, Szatmari P, Korczak D. Omega-3 fatty acid supplementation for depression in children and adolescents. Cochrane Database Syst Rev. 2024;11:CD014803. [DOI] [PubMed]

210.

Ciesielski TH, Williams SM. Low Omega-3 intake is associated with high rates of depression and preterm birth on the country level. Sci Rep. 2020;10:19749. [DOI] [PubMed] [PMC]

211.

Gabbay V, Freed RD, Alonso CM, Senger S, Stadterman J, Davison BA, et al. A Double-Blind Placebo-Controlled Trial of Omega-3 Fatty Acids as a Monotherapy for Adolescent Depression. J Clin Psychiatry. 2018;79:17m11596. [DOI] [PubMed] [PMC]

212.

McNamara RK, Strimpfel J, Jandacek R, Rider T, Tso P, Welge JA, et al. Detection and Treatment of Long-Chain Omega-3 Fatty Acid Deficiency in Adolescents with SSRI-Resistant Major Depressive Disorder. PharmaNutrition. 2014;2:38–46. [DOI] [PubMed] [PMC]

213.

Li S, Li R, Hu X, Zhang Y, Wang D, Gao Y, et al. Omega-3 supplementation improves depressive symptoms, cognitive function and niacin skin flushing response in adolescent depression: A randomized controlled clinical trial. J Affect Disord. 2024;345:394–403. [DOI] [PubMed]

214.

Smesny S, Milleit B, Schaefer MR, Hesse J, Schlögelhofer M, Langbein K, et al. Effects of omega-3 PUFA on immune markers in adolescent individuals at ultra-high risk for psychosis - Results of the randomized controlled Vienna omega-3 study. Schizophr Res. 2017;188:110–7. [DOI] [PubMed]

215.

Rangel-Huerta OD, Aguilera CM, Mesa MD, Gil A. Omega-3 long-chain polyunsaturated fatty acids supplementation on inflammatory biomakers: a systematic review of randomised clinical trials. Br J Nutr. 2012;107:S159–70. [DOI] [PubMed]

216.

Häberling I, Berger G, Schmeck K, Held U, Walitza S. Omega-3 Fatty Acids as a Treatment for Pediatric Depression. A Phase III, 36 Weeks, Multi-Center, Double-Blind, Placebo-Controlled Randomized Superiority Study. Front Psychiatry. 2019;10:863. [DOI] [PubMed] [PMC]

217.

Chang JP, Chang S, Yang H, Chen H, Chien Y, Yang B, et al. Omega-3 polyunsaturated fatty acids in cardiovascular diseases comorbid major depressive disorder - Results from a randomized controlled trial. Brain Behav Immun. 2020;85:14–20. [DOI] [PubMed]

218.

Davidson PW, Strain JJ, Myers GJ, Thurston SW, Bonham MP, Shamlaye CF, et al. Neurodevelopmental effects of maternal nutritional status and exposure to methylmercury from eating fish during pregnancy. Neurotoxicology. 2008;29:767–75. [DOI] [PubMed] [PMC]

219.

Mou Y, Blok E, Barroso M, Jansen PW, White T, Voortman T. Dietary patterns, brain morphology and cognitive performance in children: Results from a prospective population-based study. Eur J Epidemiol. 2023;38:669–87. [DOI] [PubMed] [PMC]

220.

Firth J, Solmi M, Wootton RE, Vancampfort D, Schuch FB, Hoare E, et al. A meta-review of “lifestyle psychiatry”: the role of exercise, smoking, diet and sleep in the prevention and treatment of mental disorders. World Psychiatry. 2020;19:360–80. [DOI] [PubMed] [PMC]