Международный эндокринологический журнал Том 22, №1, 2026
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Депресія, цукровий діабет 2-го типу і омега-3 поліненасичені жирні кислоти
Авторы: Сергієнко В.О., Чемерис О.М., Маркевич М.-Ю.Ю., Сергієнко О.О.
ДНП «Львівський національний медичний університет імені Данила Галицького», м. Львів, Україна
Рубрики: Эндокринология
Разделы: Справочник специалиста
Версия для печати
Ризик виникнення депресії у хворих на цукровий діабет (ЦД) 2-го типу у 1,5–2 рази вищий порівняно з особами без порушень вуглеводного обміну. Крім того, у дорослих із предіабетом частіше спостерігаються інсульти та деменція, що свідчить про початок патофізіологічних змін у центральній нервовій системі (ЦНС) ще до появи клінічних симптомів ЦД 2-го типу. Результати низки епідеміологічних досліджень свідчать, що адекватне споживання омега-3 поліненасичених жирних кислот (ω-3 ПНЖК) або їх підвищений рівень у сироватці крові корелює зі зниженим ризиком розвитку депресії. Крім того, значна кількість робіт також вказує на те, що співвідношення рівня споживання ω-3 ПНЖК і ω-6 ПНЖК обернено пропорційно пов’язане з ризиком розвитку депресивних симптомів. Результати метааналізу досліджень продемонстрували, що ω-3 ПНЖК сприяють поліпшенню глікемічного контролю та зниженню інсулінорезистентності у хворих на ЦД 2-го типу. Ω-3 ПНЖК впливають на ліпідний склад, регулюють плинність мембран і мембранні процеси в клітинах, сприяють формуванню білкових комплексів у мембранах і ліпідних доменах, впливають на нейротрансмітери та нейроендокринний екзоцитоз, підтримують активність мікроглії під час фагоцитозу. Вони здатні посилювати антиоксидантний потенціал, генерувати протизапальні метаболіти і регулювати сигнальні шляхи запалення. Ω-3 ПНЖК регулюють шляхи сигналізації, впливають на системи нейромедіаторів, модулюють експресію генів, а також беруть участь у процесах проліферації, диференціації, росту, розвитку, старіння й апоптозу. Завдяки цим механізмам ω-3 ПНЖК значно впливають на нейробіологічні процеси, пов’язані з регуляцією настрою в ЦНС. Крім того, вони сприяють поліпшенню стану при нейрозапаленні, оксидативному стресі, інсулінорезистентності, нейродегенеративних процесах, порушеннях нейропластичності, впливають на функціонування системи нейротрансмітерів. Сукупність цих ефектів може відігравати важливу роль у профілактиці та лікуванні депресії у хворих на ЦД 2-го типу. Основна мета цього огляду полягає в аналізі значення ω-3 ПНЖК у профілактиці й лікуванні коморбідних станів, зокрема депресії та ЦД 2-го типу. Окрім цього, розглядаються актуальні тенденції та окреслюються перспективні напрямки для майбутніх досліджень у цій сфері. Пошук проводився в Scopus, Science Direct (від Elsevier) і PubMed, включно з базами даних Medline. Використано ключові слова «депресія», «цукровий діабет 2-го типу», «ω-3 поліненасичені жирні кислоти». Для виявлення результатів досліджень, які не вдалося знайти під час онлайн-пошуку, використовувався ручний пошук бібліографії публікацій.
The risk of depression in patients with type 2 diabetes mellitus (T2DM) is 1.5–2 times higher than in people without carbohydrate metabolism disorders. In addition, adults with prediabetes are more likely to have strokes and dementia, which indicates the onset of pathophysiological changes in the central nervous system even before clinical manifestation of T2DM. Several epidemiological studies have shown that adequate intake of ω-3 polyunsaturated fatty acids (PUFAs) or their increased serum levels correlate with a reduced risk of depression. In addition, a significant number of studies also indicate that the ratio of ω-3 PUFA to ω-6 PUFA intake is inversely related to the risk of developing depressive symptoms. The results of a meta-analysis of studies have demonstrated that ω-3 PUFAs contribute to the improvement of glycemic control and reduction of insulin resistance in patients with T2DM. Ω-3 PUFAs affect lipid composition, regulate membrane fluidity and membrane processes in cells, promote the formation of protein complexes in membranes and lipid domains, influence neurotransmitters and neuroendocrine exocytosis, and support microglia activity during phagocytosis. They can enhance antioxidant potential, generate anti-inflammatory metabolites, and regulate inflammatory signaling pathways. ω-3 PUFAs regulate signaling pathways, affect neurotransmitter systems, modulate gene expression, and are involved in the processes of proliferation, differentiation, growth, development, aging, and apoptosis. Thanks to these mechanisms, ω-3 PUFAs have a significant impact on neurobiological processes associated with mood regulation in the central nervous system. In addition, they improve the status in neuroinflammation, oxidative stress, insulin resistance, neurodegenerative processes, neuroplasticity disorders, and influence neurotransmitter system functioning. The combination of these effects may play an important role in the prevention and treatment of depression in patients with T2DM. The main purpose of this review is to analyze the importance of ω-3 PUFAs in the prevention and treatment of comorbid conditions, including depression and T2DM. In addition, current trends are discussed, and promising areas for future research in this field are outlined. The search was conducted in Scopus, ScienceDirect (from Elsevier), and PubMed, including MEDLINE databases. The keywords used were “depression”, “type 2 diabetes mellitus”, and “ω-3 polyunsaturated fatty acids”. A manual search of the bibliography of publications was used to identify research results that could not be found during the online search.
депресія; цукровий діабет 2-го типу; ω-3 поліненасичені жирні кислоти; огляд
depression; type 2 diabetes mellitus; ω-3 polyunsaturated fatty acids; review
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- Wang F, Wang S, Zong QQ, et al. Prevalence of comorbid major depressive disorder in type 2 diabetes: a meta-analysis of compa–rative and epidemiological studies. Diabet Med. 2019 Aug;36(8):961-969. doi: 10.1111/dme.14042.
- Maida CD, Daidone M, Pacinella G, Norrito RL, Pinto A, Tuttolomondo A. Diabetes and ischemic stroke: An old and new relationship an overview of the close interaction between these diseases. Int J Mol Sci. 2022 Feb 21;23(4):2397. doi: 10.3390/ijms23042397.
- Serhiyenko VA, Serhiyenko LM, Serhiyenko AA. Features of Circadian Rhythms of Heart Rate Variability, Arterial Stiffness and Outpatient Monitoring of Blood Pressure in Diabetes Mellitus: Data, Mechanisms and Consequences. In: Sinha RP, editors. Circadian Rhythms and Their Importance. New York: Nova Science Publishers; 2022. 279-341 pp. doi: 10.52305/GXME8274.
- Serhiyenkо V, Chemerys O, Pankiv V, Serhiyenko A. Type 2 diabetes mellitus, cerebral small vessel disease and depressive disorders. International Neurological Journal. 2025 May 20;21(3):226-237. doi: 10.22141/2224-0713.21.3.2025.1178.
- Mosenzon O, Cheng AY, Rabinstein AA, Sacco S. Diabetes and stroke: What are the connections? J Stroke. 2023 Jan;25(1):26-38. doi: 10.5853/jos.2022.02306.
- Barrea L, Verde L, Colao A, Mandarino LJ, Muscogiuri G. Medical nutrition therapy for the management of type 2 diabetes mellitus. Nat Rev Endocrinol. 2025 Aug 15. doi: 10.1038/s41574-025-01161-5.
- Serhiyenko V, Serhiyenko A. Diabetic Cardiac Autonomic Neuropathy. In: Rodriguez-Saldana JR, editors. The Diabetes Text book: Clinical Principles, Patient Management and Public Health Issues. 2nd ed. Cham: Springer Nature; 2023. 939-966 pp. doi: 10.1007/978-3-031-25519-9_57.
- Sivri D, Akdevelioğlu Y. Effect of fatty acids on glucose metabo–lism and type 2 diabetes. Nutr Rev. 2025 May 1;83(5):897-907. doi: 10.1093/nutrit/nuae165.
- Serhiyenko VA, Serhiyenko LM, Serhiyenko AA. Omega-3 polyunsaturated fatty acids in the treatment of diabetic cardiovascular autonomic neuropathy: A review. In: Moore SJ, editor. Omega-3: Die–tary sources, biochemistry and impact on human health. New York: Nova Science Publishers; 2017. 79-154 pp.
- Hong Y, Jin X, Shi L. Association between polyunsaturated fatty acids and depression in women with infertility: a cross-sectio–nal study based on the National Health and Nutrition Examination Survey. Front Psychiatry. 2024 Jul 2;15:1345815. doi: 10.3389/fpsyt.2024.1345815.
- Wang M, Yan X, Li Y, et al. Association between plasma polyunsaturated fatty acids and depressive among US adults. Front Nutr. 2024 Mar 13;11:1342304. doi: 10.3389/fnut.2024.1342304.
- Zhou L, Xiong JY, Chai YQ, et al. Possible antidepressant mechanisms of omega-3 polyunsaturated fatty acids acting on the central nervous system. Front Psychiatry. 2022 Aug 31;13:933704. doi: 10.3389/fpsyt.2022.933704.
- Serefko A, Jach ME, Pietraszuk M, Świąder M, Świąder K, Szopa A. Omega-3 polyunsaturated fatty acids in depression. Int J Mol Sci. 2024 Aug 8;25(16):8675. doi: 10.3390/ijms25168675.
- Guu TW, Mischoulon D, Sarris J, et al. A multi-national, multi-disciplinary Delphi consensus study on using omega-3 polyunsaturated fatty acids (n-3 PUFAs) for the treatment of major depressive disorder. J Affect Disord. 2020 Mar 15;265:233-238. doi: 10.1016/j.jad.2020.01.050.
- Zhang Y, Liu Y, Sun J, Zhang W, Guo Z, Ma Q. Arachidonic acid metabolism in health and disease. MedComm (2020). 2023 Sep 20;4(5):e363. doi: 10.1002/mco2.363.
- Cao H, Li MY, Li G, et al. Retinoid X receptor α regulates DHA-dependent spinogenesis and functional synapse formation in vivo. Cell Rep. 2020 May 19;31(7):107649. doi: 10.1016/j.celrep.2020.
- Wang W, Zhong X, Guo J. Role of 2-series prostaglandins in the pathogenesis of type 2 diabetes mellitus and non-alcoholic fatty liver disease (review). Int J Mol Med. 2021 Jun;47(6):114. doi: 10.3892/ijmm.2021.4947.
- Bayram SŞ, Kızıltan G. The role of omega-3 polyunsaturated fatty acids in diabetes mellitus management: A narrative review. Curr Nutr Rep. 2024 Sep;13(3):527-551. doi: 10.1007/s13668-024-00561-9.
- Li M, Li Z, Fan Y. Omega-3 fatty acids: multi-target mecha–nisms and therapeutic applications in neurodevelopmental disorders and epilepsy. Front Nutr. 2025 May 30;12:1598588. doi: 10.3389/fnut.2025.1598588.
- Ashraf GM, Chatzichronis S, Alexiou A, et al. Dietary alterations in impaired mitochondrial dynamics due to neurodegeneration. Front Aging Neurosci. 2022 Jul 11;14:893018. doi: 10.3389/fnagi.2022.893018.
- Liu H, Wang S, Wang J, et al. Energy metabolism in health and diseases. Signal Transduct Target Ther. 2025 Feb 18;10(1):69. doi: 10.1038/s41392-025-02141-x.
- Choi DH, Lee SM, Park BN, et al. Omega-3 fatty acids modify drp1 expression and activate the PINK1-dependent mitophagy pathway in the kidney and heart of adenine-induced uremic rats. Biomedi–cines. 2024 Sep 15;12(9):2107. doi: 10.3390/biomedicines12092107.
- Son SH, Lee SM, Lee MH, et al. Omega-3 fatty acids upregulate SIRT1/3, activate PGC-1α via deacetylation, and induce NRF1 production in 5/6 nephrectomy rat model. Mar Drugs. 2021 Mar 26;19(4):182. doi: 10.3390/md19040182.
- Song M, Bai Y, Song F. High-fat diet and neuroinflammation: The role of mitochondria. Pharmacol Res. 2025 Feb;212:107615. doi: 10.1016/j.phrs.2025.107615.
- Janiszewska J, Ostrowska J, Szostak-Węgierek D. The influence of nutrition on adiponectin — A narrative review. Nutrients. 2021 Apr 21;13(5):1394. doi: 10.3390/nu13051394.
- Ahmadi AR, Shirani F, Abiri B, Siavash M, Haghighi S, Akbari M. Impact of omega-3 fatty acids supplementation on the gene expression of peroxisome proliferator activated receptors-γ, α and fibroblast growth factor-21 serum levels in patients with various presentation of metabolic conditions: a GRADE assessed systematic review and dose-response meta-analysis of clinical trials. Front Nutr. 2023 Nov 15;10:1202688. doi: 10.3389/fnut.2023.1202688.
- Liu J, Gao Z, Liu C, et al. Alteration of gut microbiota: New strategy for treating autism spectrum disorder. Front Cell Dev Biol. 2022 Mar 3;10:792490. doi: 10.3389/fcell.2022.792490.
- Chávez-Ortega MP, Almanza-Pérez JC, Sánchez-Muñoz F, et al. Effect of supplementation with omega-3 polyunsaturated fatty acids on metabolic modulators in skeletal muscle of rats with an obesogenic high-fat diet. Pharmaceuticals (Basel). 2024 Feb 8;17(2):222. doi: 10.3390/ph17020222.
- Jerab D, Blangero F, da Costa PCT, et al. Beneficial effects of omega-3 fatty acids on obesity and related metabolic and chronic inflammatory diseases. Nutrients. 2025 Apr 3;17(7):1253. doi: 10.3390/nu17071253.
- Wenderoth T, Feldotto M, Hernandez J, et al. Effects of omega-3 polyunsaturated fatty acids on the formation of adipokines, cytokines, and oxylipins in retroperitoneal adipose tissue of mice. Int J Mol Sci. 2024 Sep 13;25(18):9904. doi: 10.3390/ijms25189904.
- O’Connell TD, Murphy KA, Zhang N, et al. Signaling through free fatty acid receptor 4 attenuates cardiometabolic disease. Phy–siology (Bethesda). 2022 Nov 1;37(6):311-322. doi: 10.1152/phy–siol.00007.2022.
- Serhiyenko V, Serhiyenko A, Segin V, Serhiyenko L. Association of arterial stiffness, N-terminal pro-brain natriuretic peptide, insulin resistance, and left ventricular diastolic dysfunction with diabetic cardiac autonomic neuropathy. Vessel Plus. 2022 Feb 17;6:11. doi: 10.20517/2574-1209.2021.83.
- Abdalla MA, Abubaker J, Abu-Farha M, et al. Investigating the role of FABP4 in diabetes and obesity and the influence of age and ethnicity: A comprehensive analysis of a cohort from the KEDP-Study. Int J Mol Sci. 2024 Apr 23;25(9):4578. doi: 10.3390/ijms25094578.
- McTavish PV, Mutch DM. Omega-3 fatty acid regulation of lipoprotein lipase and FAT/CD36 and its impact on white adipose tissue lipid uptake. Lipids Health Dis. 2024 Nov 20;23(1):386. doi: 10.1186/s12944-024-02376-7.
- Patt M, Karkossa I, Krieg L, Massier L, et al. FGF21 and its underlying adipose tissue-liver axis inform cardiometabolic burden and improvement in obesity after metabolic surgery. EBioMedicine. 2024 Dec;110:105458. doi: 10.1016/j.ebiom.2024.105458.
- Sherratt SCR, Libby P, Bhatt DL, Mason RP. A biological rationale for the disparate effects of omega-3 fatty acids on cardiovascular disease outcomes. Prostaglandins Leukot Essent Fatty Acids. 2022 Jul;182:102450. doi: 10.1016/j.plefa.2022.102450.
- Sinha S, Haque M, Lugova H, Kumar S. The Effect of omega-3 fatty acids on insulin resistance. Life (Basel). 2023 Jun 5;13(6):1322. doi: 10.3390/life13061322.
- Serhiyenko VA, Sehin VB, Serhiyenko LM, Serhiyenko AA. Post-traumatic stress disorder, metabolic syndrome, and the autono–mic nervous system. Endokrynologia. 2023 Dec;28(4):377-392. doi: 10.31793/1680-1466.2023.28-4.377.
- Serhiyenko A, Baitsar M, Sehin V, Serhiyenko L, Kuznets V, Serhiyenko V. Post-traumatic stress disorder, insomnia, heart rate variability and metabolic syndrome (narrative review). Proc Shevchenko Sci Soc Med Sci. 2024 Jun;73(1):1-10. doi: 10.25040/ntsh2024.01.07.
- Kageyama K, Iwasaki Y, Daimon M. Hypothalamic regulation of corticotropin-releasing factor under stress and stress resilience. Int J Mol Sci. 2021 Nov 12;22(22):12242. doi: 10.3390/ijms222212242.
- Serhiyenkо VA, Chemerys OM, Pankiv VI, Serhiyenko AA. Post-traumatic stress disorder, metabolic syndrome, diabetic distress, and vitamin B1/benfotiamine. International Neurological Journal. 2025;21(1):96-107. doi: 10.22141/2224-0713.21.1.2025.1157.
- Zinkow A, Grodzicki W, Czerwińska M, Dziendzikowska K. Molecular mechanisms linking omega-3 fatty acids and the gut-brain axis. Molecules. 2024 Dec 28;30(1):71. doi: 10.3390/molecules30010071.
- Oravcova H, Katrencikova B, Garaiova I, Durackova Z, Trebaticka J, Jezova D. Stress hormones cortisol and aldosterone, and selected markers of oxidative stress in response to long-term supplementation with omega-3 fatty acids in adolescent children with depression. Antioxidants (Basel). 2022 Aug 10;11(8):1546. doi: 10.3390/antiox11081546.
- 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 Aug 4;12(8):2333. doi: 10.3390/nu12082333.
- Woźny-Rasała I, Ogłodek EA. NLRP3 inflammasome in stress-related neuropsychiatric disorders: Mechanisms of neuron-microglia-astrocyte crosstalk, HPA axis dysregulation, and therapeutic perspective. Biomolecules. 2025 Sep 19;15(9):1344. doi: 10.3390/biom15091344.
- Choi JE, Kim EY, Park Y. N-3 PUFA improved pup separation-induced postpartum depression via serotonergic pathway regu–lated by miRNA. J Nutr Biochem. 2020;84:108417. doi: 10.1016/j.jnutbio.2020.108417.
- Madison AA, Belury MA, Andridge R, et al. Omega-3 supplementation and stress reactivity of cellular aging biomarkers: an ancillary substudy of a randomized, controlled trial in midlife adults. Mol Psychiatry. 2021;26:3034-3042. doi: 10.1038/s41380-021-01077-2.
- Bhatt S, Nagappa AN, Patil CR. Role of oxidative stress in depression. Drug Discov Today. 2020;25:1270-1276. doi: 10.1016/j.drudis.2020.05.001.
- Głombik K, Budziszewska B, Basta-Kaim A. Mitochondria-targeting therapeutic strategies in the treatment of depression. Mitochondrion. 2021 May;58:169-178. doi: 10.1016/j.mito.2021.03.006.
- Serhiyenko VA, Serhiyenko LM, Sehin VB, Serhiyenko AA. Pathophysiological and clinical aspects of the circadian rhythm of arterial stiffness in diabetes mellitus: A minireview. Endocr Regul. 2022 Oct 20;56(4):284-294. doi: 10.2478/enr-2022-0031.
- Bouvier E, Brouillard F, Molet J, et al. Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression. Mol Psychiatry. 2017 Dec;22(12):1701-1713. doi: 10.1038/mp.2016.144.
- Heshmati J, Morvaridzadeh M, Maroufizadeh S, et al. Omega-3 fatty acids supplementation and oxidative stress parameters: A systematic review and meta-analysis of clinical trials. Pharmacol Res. 2019 Nov;149:104462. doi: 10.1016/j.phrs.2019.104462.
- Golpour P, Nourbakhsh M, Mazaherioun M, Janani L, Nourbakhsh M, Yaghmaei P. Improvement of NRF2 gene expression and antioxidant status in patients with type 2 diabetes mellitus after supplementation with omega-3 polyunsaturated fatty acids: A double-blind randomised placebo-controlled clinical trial. Diabetes Res Clin Pract. 2020 Apr;162:108120. doi: 10.1016/j.diabres.2020.108120.
- Zgórzyńska E, Dziedzic B, Gorzkiewicz A, et al. Omega-3 polyunsaturated fatty acids improve the antioxidative defense in rat astrocytes via an Nrf2-dependent mechanism. Pharmacol Rep. 2017 Oct;69(5):935-942. doi: 10.1016/j.pharep.2017.04.009.
- Borsini A, Stangl D, Jeffries AR, Pariante CM, Thuret S. The role of omega-3 fatty acids in preventing glucocorticoid-induced reduction in human hippocampal neurogenesis and increase in apoptosis. Transl Psychiatry. 2020 Jul 7;10(1):219. doi: 10.1038/s41398-020-00908-0.
- Suneson K, Söderberg Veibäck G, Lindahl J, et al. Omega-3 fatty acids for inflamed depression — A match/mismatch study. Brain Behav Immun. 2024 May;118:192-201. doi: 10.1016/j.bbi.2024.02.029.
- Réus GZ, Maciel AL, Abelaira HM, et al. ω-3 and folic acid act against depressive-like behavior and oxidative damage in the brain of rats subjected to early- or late-life stress. Nutrition. 2018 Sep;53:120-133. doi: 10.1016/j.nut.2018.03.006.
- Tang M, Liu T, Jiang P, Dang R. The interaction between autophagy and neuroinflammation in major depressive disorder: from pathophysiology to therapeutic implications. Pharmacol Res. 2021;168:105586. doi: 10.1016/j.phrs.2021.105586.
- Serhiyenko VA, Sehin VB, Pankiv VI, Serhiyenko AA. Post-traumatic stress disorder, dyssomnias, and metabolic syndrome. Mìžnarodnij endokrinologìčnij žurnal. 2024 Mar;20(1):58-67. doi: 10.22141/2224-0721.20.1.2024.1359.
- Xiao K, Luo Y, Liang X, et al. Beneficial effects of running exercise on hippocampal microglia and neuroinflammation in chronic unpredictable stress-induced depression model rats. Transl Psychiatry. 2021 Sep 6;11(1):461. doi: 10.1038/s41398-021-01571-9.
- Li Z, Ruan M, Chen J, Fang Y. Major depressive disorder: Advances in neuroscience research and translational applications. Neurosci Bull. 2021 Jun;37(6):863-880. doi: 10.1007/s12264-021-00638-3.
- Silberstein S, Liberman AC, Dos Santos Claro PA, Ugo MB, Deussing JM, Arzt E. Stress-related brain neuroinflammation impact in depression: Role of the corticotropin-releasing hormone system and P2X7 receptor. Neuroimmunomodulation. 2021;28(2):52-60. doi: 10.1159/000515130.
- Hassamal S. Chronic stress, neuroinflammation, and depression: An overview of pathophysiological mechanisms and emerging anti-inflammatories. Front Psychiatry. 2023 May 11;14:1130989. doi: 10.3389/fpsyt.2023.1130989.
- Peng S, Peng Z, Qin M, et al. Targeting neuroinflammation: The therapeutic potential of ω-3 PUFAs in substance abuse. Nutrition. 2021 Mar;83:111058. doi: 10.1016/j.nut.2020.111058.
- Madore C, Leyrolle Q, Morel L, et al. Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain. Nat Commun. 2020;11:6133. doi: 10.1038/s41467-020-19861-z.
- Malau IA, Chang JP-C, Lin Y-W, Chang C-C, Chiu W-C, Su K-P. Omega-3 fatty acids and neuroinflammation in depression: Targeting damage-associated molecular patterns and neural biomar–kers. Cells. 2024;13(21):1791. doi: 10.3390/cells13211791.
- McNamara RK, Almeida DM. Omega-3 polyunsaturated fatty acid deficiency and progressive neuropathology in psychiatric disorders: a review of translational evidence and candidate mechanisms. Harv Rev Psychiatry. 2019;27:94. doi: 10.1097/HRP.0000000000000199.
- Luan X, Wang X, Shi Y, et al. Abnormalities of lipid metabolism in the progression and treatment of depression. Front Psychiatry. 2025 May 29;16:1589663. doi: 10.3389/fpsyt.2025.1589663.
- Hussain M, Kumar P, Khan S, Gordon DK, Khan S. Simila–rities between depression and neurodegenerative diseases: pathophysio–logy, challenges in diagnosis and treatment options. Cureus. 2020 Nov 21;12(11):e11613. doi: 10.7759/cureus.11613.
- Han K, Ham B, Kim Y. Development of neuroimagingbased biomarkers in major depression. Adv Exp Med Biol. 2021;1305:85-99. doi: 10.1007/978-981-33-6044-0_6.
- Correia AS, Cardoso A, Vale N. BDNF unveiled: Exploring its role in major depression disorder serotonergic imbalance and associated stress conditions. Pharmaceutics. 2023 Aug 3;15(8):2081. doi: 10.3390/pharmaceutics15082081.
- Papa D, Ingenito A, von Gal A, De Pandis MF, Piccardi L. Relationship between depression and neurodegeneration: Risk factor, prodrome, consequence, or something else? A scoping review. Biome–dicines. 2025 Apr 23;13(5):1023. doi: 10.3390/biomedicines13051023.
- Crump C, Sieh W, Vickrey BG, Edwards AC, Sundquist J, Sundquist K. Risk of depression in persons with Alzheimer’s di–sease: A national cohort study. Alzheimers Dement (Amst). 2024 Apr 14;16(2):e12584. doi: 10.1002/dad2.12584.
- Khedr EM, Abdelrahman AA, Elserogy Y, Zaki AF, Gamea A. Depression and anxiety among patients with Parkinson’s disease: frequency, risk factors, and impact on quality of life. Egypt J Neurol Psych. 2020;56:1-9. doi: 10.1186/s41983-020-00253-5.
- Tomaszewski N, He X, Solomon V, Lee M, et al. Effect of APOE genotype on plasma docosahexaenoic acid (DHA), eicosapentaenoic acid, arachidonic acid, and hippocampal volume in the Alzheimer’s disease cooperative study-sponsored DHA clinical trial. J Alzheimers Dis. 2020;74:975-990. doi: 10.3233/JAD-191017.
- Yu JZ, Wang J, Sheridan SD, Perlis RH, Rasenick MM. N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of camp in patient-derived neural stem cells. Mol Psychiatry. 2020;26:4605-4615. doi: 10.1038/s41380-020-0786-5.
- Colucci-D’Amato L, Speranza L, Volpicelli F. Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer. Int J Mol Sci. 2020;21:7777. doi: 10.3390/ijms21207777.
- Wu SK, Chen WJ, Chang JP, et al. Personalized medicine of omega-3 fatty acids in depression treatment in obese and metabolically dysregulated patients. J Pers Med. 2023 Jun 15;13(6):1003. doi: 10.3390/jpm13061003.
- Yang T, Nie Z, Shu H, et al. The role of BDNF on neural plasticity in depression. Front Cell Neurosci. 2020;14:82. doi: 10.3389/fncel.2020.00082.
- Aleksandrova LR, Phillips AG. Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics. Trends Pharmacol Sci. 2021 Nov;42(11):929-942. doi: 10.1016/j.tips.2021.08.003.
- Lo Van A, Hachem M, Lagarde M, Bernoud-Hubac N. Omega-3 docosahexaenoic acid is a mediator of fate-decision of adult neural stem cells. Int J Mol Sci. 2019 Aug 30;20(17):4240. doi: 10.3390/ijms20174240.
- Akerele OA, Cheema SK. Maternal diet high in omega-3 fatty acids upregulate genes involved in neurotrophin signalling in fetal brain during pregnancy in C57BL/6 mice. Neurochem Int. 2020 Sep;138:104778. doi: 10.1016/j.neuint.2020.104778.
- Serrano M, Saumell-Esnaola M, Ocerin G, et al. Impact of omega-3 on endocannabinoid system expression and function, enhancing cognition and behavior in male mice. Nutrients. 2024 Dec 17;16(24):4344. doi: 10.3390/nu16244344.
- Zhao T, Liu T, Wang L, Xie K, Tang H, Tang M. Dysfunction of neurotransmitter metabolism is associated with the severity of depression in first-diagnosed, drug-naïve depressed patients. J Affect Disord. 2024 Mar 15;349:332-341. doi: 10.1016/j.jad.2024.01.023.
- Serhiyenko VA, Sehin VB, Serhiyenko LM, Serhiyenko AA. Post-traumatic stress disorder, metabolic syndrome, and chronic low-grade inflammation: A narrative review. Problemi Endocrinnoi Patologii. 2024 Mar 14;81(1):77-83. doi: 10.21856/j-PEP.2024.1.10.
- Bej E, Cesare P, Volpe AR, d’Angelo M, Castelli V. Oxidative stress and neurodegeneration: Insights and therapeutic strategies for Parkinson’s Disease. Neurol Int. 2024;16(3):502-517. doi: 10.3390/neurolint16030037.
- Balistreri CR, Monastero R. Neuroinflammation and neurodegenerative diseases: How much do we still not know? Brain Sci. 2023 Dec 23;14(1):19. doi: 10.3390/brainsci14010019.
- Sic A, Bogicevic M, Brezic N, Nemr C, Knezevic NN. Chronic stress and headaches: The role of the HPA axis and autonomic nervous system. Biomedicines. 2025 Feb 13;13(2):463. doi: 10.3390/biome–dicines13020463.
- Sălcudean A, Bodo CR, Popovici RA, et al. Neuroinflammation — A crucial factor in the pathophysiology of depression — a comprehensive review. Biomolecules. 2025 Mar 30;15(4):502. doi: 10.3390/biom15040502.
- Pathak S, Nadar R, Kim S, et al. The influence of kynurenine metabolites on neurodegenerative pathologies. Int J Mol Sci. 2024 Jan 10;25(2):853. doi: 10.3390/ijms25020853.
- Xu R, Molenaar AJ, Chen Z, Yuan Y. Mode and mechanism of action of omega-3 and omega-6 unsaturated fatty acids in chronic diseases. Nutrients. 2025 Apr 30;17(9):1540. doi: 10.3390/nu17091540.
- Borrego-Ruiz A, Borrego JJ. Plant-derived nutraceuticals in mental health and brain function: Mechanisms of action and therapeutic potential. Int J Mol Sci. 2025 Sep 11;26(18):8849. doi: 10.3390/ijms26188849.
- Yin Y, Ju T, Zeng D, et al. “Inflamed” depression: A review of the interactions between depression and inflammation and current anti-inflammatory strategies for depression. Pharmacol Res. 2024 Sep;207:107322. doi: 10.1016/j.phrs.2024.107322.
- Yassin LK, Nakhal MM, Alderei A, et al. Exploring the microbiota-gut-brain axis: impact on brain structure and function. Front Neuroanat. 2025 Feb 12;19:1504065. doi: 10.3389/fnana.2025.1504065.
- Xu J, Lu Y. The microbiota-gut-brain axis and central nervous system diseases: from mechanisms of pathogenesis to therapeutic strategies. Front Microbiol. 2025 Jun 13;16:1583562. doi: 10.3389/fmicb.2025.1583562.
- You M, Chen N, Yang Y, et al. The gut microbiota-brain axis in neurological disorders. MedComm (2020). 2024 Jul 20;5(8):e656. doi: 10.1002/mco2.656.
- Al-Ewaidat OA, Gogia S, Naffaa MM. Omega-3 PUFAs: A multifaceted approach to lifespan brain health, neurodevelopment, and precision therapeutics with implications for ASD, ADHD, and cognitive function. Dis Res. 2025;5(2):77-99. doi: 10.54457/DR.202501005.
- Ribichini E, Scalese G, Mocci C, Severi C. Gut-brain axis and psychopathology: Exploring the impact of diet with a focus on the Low-FODMAP Approach. Nutrients. 2024;16(20):3515. doi: 10.3390/nu16203515.
- Usuda H, Okamoto T, Wada K. Leaky gut: Effect of dietary fiber and fats on microbiome and intestinal barrier. Int J Mol Sci. 2021 Jul 16;22(14):7613. doi: 10.3390/ijms22147613.
- Liu XF, Shao JH, Liao YT, et al. Regulation of short-chain fatty acids in the immune system. Front Immunol. 2023 May 5;14:1186892. doi: 10.3389/fimmu.2023.1186892.
- Sittipo P, Choi J, Lee S, Lee YK. The function of gut microbiota in immune-related neurological disorders: a review. J Neuroinflammation. 2022 Jun 15;19(1):154. doi: 10.1186/s12974-022-02510-1.
- Yang R, Wang L, Jin K, et al. 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. 2022 Jul 12;9:876152. doi: 10.3389/fnut.2022.876152.
- Doherty M, Foley KR, Schloss J. Complementary and alternative medicine for Autism — A systematic review. J Autism Dev Disord. 2025 Oct;55(10):3689-3699. doi: 10.1007/s10803-024-06449-5.
- Tian J, Zhang Y, Zhao X. The effects and mechanisms of n-3 and n-6 polyunsaturated fatty acids in the central nervous system. Cell Mol Neurobiol. 2025 Mar 17;45(1):25. doi: 10.1007/s10571-025-01543-3.
- Li J, Lin YC, Zuo HL, et al. Dietary omega-3 PUFAs in metabolic disease research: A decade of omics-enabled insights (2014-2024). Nutrients. 2025 May 28;17(11):1836. doi: 10.3390/nu17111836.
- Bodur M, Yilmaz B, Agagunduz D, Ozogul T. Immunomodulatory effects of omega-3 fatty acids: Mechanistic insights and health implications. Mol Nutr Food Res. 2025;69(10):e202400752. doi: 10.1002/mnfr.202400752.
- Xue Y, Wang L, Liu T, et al. Omega-3 polyunsaturated fatty acids supplementation improves memory in first-diagnosed, drug-naïve patients with depression: Secondary analysis of data from a randomi–zed controlled trial. J Affect Disord. 2024 Apr 1;350:403-410. doi: 10.1016/j.jad.2024.01.149.
- 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 Nov 12;10(1):19749. doi: 10.1038/s41598-020-76552-x.
- Aguilar M, Alberti KGMM, Amiel SA, et al. Leitfaden zu typ-2-diabetes mellitus/Guide for type 2 diabetes mellitus (Review). Diabetes und Stoffwechsel. 2000 Mar 20;9(2):104-136. ISSN: 09420037.
- Banović Fuentes J, Beara I, Torović L. Regulatory compliance of health claims on omega-3 fatty acid food supplements. Foods. 2025;14(1):67. doi: 10.3390/foods14010067.
- D’Angelo S, Motti ML, Meccariello R. ω-3 and ω-6 polyunsaturated fatty acids, obesity and cancer. Nutrients. 2020;12(9):2751. doi: 10.3390/nu12092751.
- Wang L, Huang X, Sun M, et al. New light on ω-3 polyunsaturated fatty acids and diabetes debate: A population pharmacokinetic-pharmacodynamic modelling and intake threshold study. Nutr Diabetes. 2024 Mar 4;14(1):8. doi: 10.1038/s41387-024-00262-w.
