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2000
Volume 26, Issue 14
  • ISSN: 1389-4501
  • E-ISSN: 1873-5592

Abstract

Depression is a debilitating psychiatric disorder characterized by loss of interest, anhedonia, and social isolation, which is projected to become the leading cause of disability worldwide by 2030. Despite the greater economic and social burden imposed by depression, the precise pathophysiology underlying the development of depression remains elusive. Betaine (N, N, N-trimethylglycine), an amino acid derivative, is widely distributed in various animals and plants and has been shown to have numerous beneficial effects, including antioxidant activities, anti-inflammatory functions, regulation of energy metabolism, and reduction of endoplasmic reticulum stress. It has been used to treat Alcohol-Associated Liver Disease (AALD), type 2 diabetes, cancer, obesity, and Alzheimer's Disease (AD). Interestingly, accumulating evidence has shown that betaine exerts a significant role in alleviating depressive-like behavior in patients and animals resulting from chronic stress. Although the antidepressant effects of betaine have not been compared with traditional antidepressants with insufficient verification, based on the neurobiological mechanisms of depression, it may be a potential alternative medicine for the treatment of depression. This is the first review aiming to provide a comprehensive overview of the remarkable effects of betaine in the pathophysiology of depression. These pieces of evidence are of great importance for deepening our understanding of the antidepressant mechanism of betaine, so as to develop betaine supplements for the supplementary treatment of depression.

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2025-08-27
2026-02-01
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References

  1. Depression, other common mental disorders: Global health estimates.Geneva World Health Organization2017241
    [Google Scholar]
  2. ZhangY. ChenY. MaL. Depression and cardiovascular disease in elderly: Current understanding.J. Clin. Neurosci.2018471510.1016/j.jocn.2017.09.02229066229
    [Google Scholar]
  3. GrahamN. SmithD.J. Comorbidity of depression and anxiety disorders in patients with hypertension.J. Hypertens.201634339739810.1097/HJH.000000000000085026818922
    [Google Scholar]
  4. CarneyR.M. FreedlandK.E. New perspectives on treatment of depression in coronary heart disease.Psychosom. Med.202385647447810.1097/PSY.000000000000121937234020
    [Google Scholar]
  5. TasnimS. AunyF.M. HassanY. YesminR. AraI. MohiuddinM.S. KaggwaM.M. GozalD. MamunM.A. Antenatal depression among women with gestational diabetes mellitus: A pilot study.Reprod. Health20221917110.1186/s12978‑022‑01374‑135305655
    [Google Scholar]
  6. LiZ. RuanM. ChenJ. FangY. Major depressive disorder: Advances in neuroscience research and translational applications.Neurosci. Bull.202137686388010.1007/s12264‑021‑00638‑333582959
    [Google Scholar]
  7. QiW. JinX. GuanW. Purinergic P2X7 receptor as a potential therapeutic target in depression.Biochem. Pharmacol.202421911595910.1016/j.bcp.2023.11595938052270
    [Google Scholar]
  8. GuanW. NiM.X. GuH.J. YangY. CREB: A promising therapeutic target for treating psychiatric disorders.Curr. Neuropharmacol.202422142384240110.2174/1570159X2266624020611183838372284
    [Google Scholar]
  9. LiuP. LiuZ. WangJ. WangJ. GaoM. ZhangY. YangC. ZhangA. LiG. LiX. LiuS. LiuL. SunN. ZhangK. Immunoregulatory role of the gut microbiota in inflammatory depression.Nat. Commun.2024151300310.1038/s41467‑024‑47273‑w38589368
    [Google Scholar]
  10. CuijpersP. van StratenA. AnderssonG. van OppenP. Psychotherapy for depression in adults: A meta-analysis of comparative outcome studies.J. Consult. Clin. Psychol.200876690992210.1037/a001307519045960
    [Google Scholar]
  11. KennedyS.H. LamR.W. McIntyreR.S. TourjmanS.V. BhatV. BlierP. HasnainM. JollantF. LevittA.J. MacQueenG.M. McInerneyS.J. McIntoshD. MilevR.V. MüllerD.J. ParikhS.V. PearsonN.L. RavindranA.V. UherR. Canadian network for mood and anxiety treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder.Can. J. Psychiatry201661954056010.1177/070674371665941727486148
    [Google Scholar]
  12. CalderA.E. HaslerG. Towards an understanding of psychedelic-induced neuroplasticity.Neuropsychopharmacology202348110411210.1038/s41386‑022‑01389‑z36123427
    [Google Scholar]
  13. ChenM. MaS. LiuH. DongY. TangJ. NiZ. TanY. DuanC. LiH. HuangH. LiY. CaoX. LingleC.J. YangY. HuH. Brain region–specific action of ketamine as a rapid antidepressant.Science20243856709eado701010.1126/science.ado701039116252
    [Google Scholar]
  14. ShethS.A. BijankiK.R. MetzgerB. AllawalaA. PirtleV. AdkinsonJ.A. MyersJ. MathuraR.K. OswaltD. TsolakiE. XiaoJ. NoeckerA. StruttA.M. CohnJ.F. McIntyreC.C. MathewS.J. BortonD. GoodmanW. PouratianN. Deep brain stimulation for depression informed by intracranial recordings.Biol. Psychiatry202292324625110.1016/j.biopsych.2021.11.00735063186
    [Google Scholar]
  15. RuniaN. BergfeldI.O. de KwaastenietB.P. LuigjesJ. van LaarhovenJ. NottenP. BeuteG. van den MunckhofP. SchuurmanR. DenysD. van WingenG.A. Deep brain stimulation normalizes amygdala responsivity in treatment-resistant depression.Mol. Psychiatry20232862500250710.1038/s41380‑023‑02030‑136991129
    [Google Scholar]
  16. OlivaV. LippiM. PaciR. Del FabroL. DelvecchioG. BrambillaP. De RonchiD. FanelliG. SerrettiA. Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: A systematic review and meta-analysis.Prog. Neuropsychopharmacol. Biol. Psychiatry202110911026610.1016/j.pnpbp.2021.11026633549697
    [Google Scholar]
  17. HealyD. Antidepressants and sexual dysfunction: A history.J. R. Soc. Med.2020113413313510.1177/014107681989929931972096
    [Google Scholar]
  18. Alonso-PedreroL. Bes-RastrolloM. MartiA. Effects of antidepressant and antipsychotic use on weight gain: A systematic review.Obes. Rev.201920121680169010.1111/obr.1293431524318
    [Google Scholar]
  19. DayC.R. KempsonS.A. Betaine chemistry, roles, and potential use in liver disease.Biochim. Biophys. Acta, Gen. Subj.2016186061098110610.1016/j.bbagen.2016.02.00126850693
    [Google Scholar]
  20. JinM. ShenY. PanT. ZhuT. LiX. XuF. BetancorM.B. JiaoL. TocherD.R. ZhouQ. Dietary betaine mitigates hepatic steatosis and inflammation induced by a high-fat-diet by modulating the sirt1/srebp-1/pparɑ pathway in juvenile black seabream (acanthopagrus schlegelii).Front. Immunol.20211269472010.3389/fimmu.2021.69472034248992
    [Google Scholar]
  21. HaberboschL. KierszniowskaS. WillmitzerL. MaiK. SprangerJ. MaurerL. 5-Aminovaleric acid betaine predicts impaired glucose metabolism and diabetes.Nutr. Diabetes20231311710.1038/s41387‑023‑00245‑337730732
    [Google Scholar]
  22. LiQ. QuM. WangN. WangL. FanG. YangC. Betaine protects rats against ischemia/reperfusion injury-induced brain damage.J. Neurophysiol.2022127244445110.1152/jn.00400.202135020521
    [Google Scholar]
  23. KettunenH. TiihonenK. PeuranenS. SaarinenM.T. RemusJ.C. Dietary betaine accumulates in the liver and intestinal tissue and stabilizes the intestinal epithelial structure in healthy and coccidia-infected broiler chicks.Comp. Biochem. Physiol. A Mol. Integr. Physiol.2001130475976910.1016/S1095‑6433(01)00410‑X11691612
    [Google Scholar]
  24. CraigS.A.S. Betaine in human nutrition.Am. J. Clin. Nutr.200480353954910.1093/ajcn/80.3.53915321791
    [Google Scholar]
  25. SchwahnB.C. HafnerD. HohlfeldT. BalkenholN. LaryeaM.D. WendelU. Pharmacokinetics of oral betaine in healthy subjects and patients with homocystinuria.Br. J. Clin. Pharmacol.200355161310.1046/j.1365‑2125.2003.01717.x12534635
    [Google Scholar]
  26. KempsonS.A. ZhouY. DanboltN.C. The betaine/GABA transporter and betaine: Roles in brain, kidney, and liver.Front. Physiol.2014515910.3389/fphys.2014.0015924795654
    [Google Scholar]
  27. LeverM. SizelandP.C.B. BasonL.M. HaymanC.M. ChambersS.T. Glycine betaine and proline betaine in human blood and urine.Biochim. Biophys. Acta, Gen. Subj.19941200325926410.1016/0304‑4165(94)90165‑18068711
    [Google Scholar]
  28. LeverM. SizelandP.C.B. BasonL.M. HaymanC.M. RobsonR.A. ChambersS.T. Abnormal glycine betaine content of the blood and urine of diabetic and renal patients.Clin. Chim. Acta19942301697910.1016/0009‑8981(94)90090‑67850995
    [Google Scholar]
  29. SunJ. WenS. ZhouJ. DingS. Association between malnutrition and hyperhomocysteine in Alzheimer’s disease patients and diet intervention of betaine.J. Clin. Lab. Anal.2017315e2209010.1002/jcla.2209028671332
    [Google Scholar]
  30. ZhangA. PanC. WuM. LinY. ChenJ. ZhongN. ZhangR. PuL. HanL. PanH. Causal association between plasma metabolites and neurodegenerative diseases.Prog. Neuropsychopharmacol. Biol. Psychiatry202413411106710.1016/j.pnpbp.2024.11106738908505
    [Google Scholar]
  31. Di PierroF. OrsiR. SettembreR. Role of betaine in improving the antidepressant effect of S-adenosyl-methionine in patients with mild-to-moderate depression.J. Multidiscip. Healthc.20158394510.2147/JMDH.S7776625653537
    [Google Scholar]
  32. MiaoM. DuJ. CheB. GuoY. ZhangJ. JuZ. XuT. ZhongX. ZhangY. ZhongC. Circulating choline pathway nutrients and depression after ischemic stroke.Eur. J. Neurol.202229245946810.1111/ene.1513334611955
    [Google Scholar]
  33. MedeirosG.C. RoyD. KontosN. BeachS.R. Post-stroke depression: A 2020 updated review.Gen. Hosp. Psychiatry202066708010.1016/j.genhosppsych.2020.06.01132717644
    [Google Scholar]
  34. MitroS.D. Larrabure-TorrealvaG.T. SanchezS.E. MolsberryS.A. WilliamsM.A. ClishC. GelayeB. Metabolomic markers of antepartum depression and suicidal ideation.J. Affect. Disord.202026242242810.1016/j.jad.2019.11.06131744743
    [Google Scholar]
  35. ChernonosovA.A. MednovaI.A. LevchukL.A. MazurenkoE.O. RoschinaO.V. SimutkinG.G. BokhanN.A. KovalV.V. IvanovaS.A. Untargeted plasma metabolomic profiling in patients with depressive disorders: A preliminary study.Metabolites202414211010.3390/metabo1402011038393002
    [Google Scholar]
  36. LimveeraprajakN. NakhawatchanaS. VisukamolA. SiripakkaphantC. SuttajitS. SrisurapanontM. Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta- analysis.Prog. Neuropsychopharmacol. Biol. Psychiatry202413211098510.1016/j.pnpbp.2024.11098538423354
    [Google Scholar]
  37. JiC. KaplowitzN. Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice.Gastroenterology200312451488149910.1016/S0016‑5085(03)00276‑212730887
    [Google Scholar]
  38. ArumugamM.K. ChavaS. PerumalS.K. PaalM.C. RasineniK. GanesanM. DonohueT.M.Jr OsnaN.A. KharbandaK.K. Acute ethanol-induced liver injury is prevented by betaine administration.Front. Physiol.20221394014810.3389/fphys.2022.94014836267591
    [Google Scholar]
  39. Di PierroF. SettembreR. Preliminary results of a randomized controlled trial carried out with a fixed combination of S-adenosyl-L-methionine and betaine versus amitriptyline in patients with mild depression.Int. J. Gen. Med.20158737810.2147/IJGM.S7951825678811
    [Google Scholar]
  40. van LeeL. QuahP.L. SawS.M. YapF.K.P. GodfreyK.M. ChongY.S. MeaneyM.J. ChenH. ChongM.F.F. Maternal choline status during pregnancy, but not that of betaine, is related to antenatal mental well-being: The growing up in Singapore toward healthy outcomes cohort.Depress. Anxiety2017341087788710.1002/da.2263728471488
    [Google Scholar]
  41. KageyamaY. KasaharaT. MorishitaH. MatagaN. DeguchiY. TaniM. KurodaK. HattoriK. YoshidaS. InoueK. KatoT. Search for plasma biomarkers in drug-free patients with bipolar disorder and schizophrenia using metabolome analysis.Psychiatry Clin. Neurosci.201771211512310.1111/pcn.1246127676126
    [Google Scholar]
  42. HuiR. XuJ. ZhouM. XieB. ZhouM. ZhangL. CongB. MaC. WenD. Betaine improves METH-induced depressive-like behavior and cognitive impairment by alleviating neuroinflammation via NLRP3 inflammasome inhibition.Prog. Neuropsychopharmacol. Biol. Psychiatry202413511109310.1016/j.pnpbp.2024.11109339029648
    [Google Scholar]
  43. LiW. AliT. HeK. LiuZ. ShahF.A. RenQ. LiuY. JiangA. LiS. Ibrutinib alleviates LPS-induced neuroinflammation and synaptic defects in a mouse model of depression.Brain Behav. Immun.202192102410.1016/j.bbi.2020.11.00833181270
    [Google Scholar]
  44. ZhangY. JiaJ. Betaine mitigates amyloid-β-associated neuroinflammation by suppressing the NLRP3 and NF-κB signaling pathways in microglial cells.J. Alzheimers Dis.202394s1S9S1910.3233/JAD‑23006437334594
    [Google Scholar]
  45. SookoianS. PuriP. CastañoG.O. ScianR. MirshahiF. SanyalA.J. PirolaC.J. Nonalcoholic steatohepatitis is associated with a state of betaine-insufficiency.Liver Int.201737461161910.1111/liv.1324927614103
    [Google Scholar]
  46. DuncanZ. KippenR. SuttonK. WardB. AgiusP.A. QuinnB. DietzeP. Correlates of anxiety and depression in a community cohort of people who smoke methamphetamine.Aust. N. Z. J. Psychiatry202256896497310.1177/0004867421104815234558302
    [Google Scholar]
  47. AlgaidiS.A. ChristieL.A. JenkinsonA.M. WhalleyL. RiedelG. PlattB. Long-term homocysteine exposure induces alterations in spatial learning, hippocampal signalling and synaptic plasticity.Exp. Neurol.2006197182110.1016/j.expneurol.2005.07.00316095594
    [Google Scholar]
  48. ZhangM. WangX.L. ShiH. MengL.Q. QuanH.F. YanL. YangH.F. PengX.D. Betaine inhibits NLRP3 inflammasome hyperactivation and regulates microglial M1/M2 phenotypic differentiation, thereby attenuating lipopolysaccharide-induced depression-like behavior.J. Immunol. Res.2022202211410.1155/2022/931343636339940
    [Google Scholar]
  49. QuY. ZhangK. PuY. ChangL. WangS. TanY. WangX. ZhangJ. OhnishiT. YoshikawaT. HashimotoK. Betaine supplementation is associated with the resilience in mice after chronic social defeat stress: A role of brain–gut–microbiota axis.J. Affect. Disord.2020272667610.1016/j.jad.2020.03.09532379622
    [Google Scholar]
  50. MullinsP.M. YongR.J. BhattacharyyaN. Associations between chronic pain, anxiety, and depression among adults in the United States.Pain Pract.202323658959410.1111/papr.1322036881021
    [Google Scholar]
  51. BoccellaS. PerroneM. FuscoA. BonsaleR. InfantinoR. NuzzoS. PecoraroG. RicciardiF. Maria MoraceA. PetrilloG. LeoneI. FranzeseM. de NovellisV. GuidaF. SalvatoreM. MaioneS. LuongoL. Spinal neuronal activity and neuroinflammatory component in a mouse model of CFA-induced vestibulodynia.Brain Behav. Immun.202411940841510.1016/j.bbi.2024.04.01238636564
    [Google Scholar]
  52. LiangY. ChenL. HuangY. XieL. LiuX. ZhouW. CaoW. ChenZ. ZhongX. Betaine eliminates CFA-induced depressive-like behaviour in mice may be through inhibition of microglia and astrocyte activation and polarization.Brain Res. Bull.202420611086310.1016/j.brainresbull.2023.11086338145759
    [Google Scholar]
  53. ShiM.M. XuX.F. SunQ.M. LuoM. LiuD.D. GuoD.M. ChenL. ZhongX.L. XuY. CaoW.Y. Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice.Phytother. Res.202337104755477010.1002/ptr.794437846157
    [Google Scholar]
  54. YoungL.T. WarshJ.J. KishS.J. ShannakK. HornykeiwiczO. Reduced brain 5-HT and elevated NE turnover and metabolites in bipolar affective disorder.Biol. Psychiatry199435212112710.1016/0006‑3223(94)91201‑77513191
    [Google Scholar]
  55. KimSJ LeeMS KimJH LeeTH ShimI Antidepressant-like effects of Lycii radicis cortex and betaine in the forced swimming test in rats.Biomol Ther2013Jan211798310.4062/biomolther.2012.07224009863
    [Google Scholar]
  56. LeeD.S. JoH.G. KimM.J. LeeH. CheongS.H. Antioxidant and anti-stress effects of taurine against electric foot-shock-induced acute stress in rats.Adv. Exp. Med. Biol.2019115518519610.1007/978‑981‑13‑8023‑5_1731468397
    [Google Scholar]
  57. BouvierE. BrouillardF. MoletJ. ClaverieD. CabungcalJ-H. CrestoN. DoligezN. RivatC. DoK.Q. BernardC. BenolielJ-J. BeckerC. Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression.Mol. Psychiatry201722121701171310.1038/mp.2016.14427646262
    [Google Scholar]
  58. MichelT.M. FrangouS. ThiemeyerD. CamaraS. JecelJ. NaraK. BrunklausA. ZoechlingR. RiedererP. Evidence for oxidative stress in the frontal cortex in patients with recurrent depressive disorder—A postmortem study.Psychiatry Res.20071511-214515010.1016/j.psychres.2006.04.01317296234
    [Google Scholar]
  59. MichelT.M. ThomeJ. MartinD. NaraK. ZwerinaS. TatschnerT. WeijersH.G. KoutsilieriE. Cu, Zn- and Mn-superoxide dismutase levels in brains of patients with schizophrenic psychosis.J. Neural Transm.200411191191120110.1007/s00702‑004‑0160‑915338334
    [Google Scholar]
  60. ChenL. LiuD. MaoM. LiuW. WangY. LiangY. CaoW. ZhongX. Betaine ameliorates acute sever ulcerative colitis by inhibiting oxidative stress induced inflammatory pyroptosis.Mol. Nutr. Food Res.20226622220034110.1002/mnfr.20220034136069237
    [Google Scholar]
  61. JeyhoonabadiM. AlimoahmmadiS. HassanpourS. HashemniaM. Betaine ameliorates depressive-like behaviors in zinc oxide nanoparticles exposed mice.Biol. Trace Elem. Res.2022200114771478110.1007/s12011‑021‑03068‑434993911
    [Google Scholar]
  62. AttiaH. NounouH. ShalabyM. Zinc oxide nanoparticles induced oxidative DNA damage, inflammation and apoptosis in rat’s brain after oral exposure.Toxics2018622910.3390/toxics602002929861430
    [Google Scholar]
  63. HaramipourP. AsghariA. HassanpourS. JahandidehA. Anti-depressant effect of betaine mediates via nitrergic and serotoninergic systems in ovariectomized mice.Arch. Razi Inst.20217651404141710.22092/ari.2020.352221.155335355756
    [Google Scholar]
  64. XuQ. SunL. ChenQ. JiaoC. WangY. LiH. XieJ. ZhuF. WangJ. ZhangW. XieL. WuH. ZuoZ. ChenX. Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model.Brain Behav. Immun.202411922023510.1016/j.bbi.2024.04.00238599497
    [Google Scholar]
  65. SalesAJ MacielIS CrestaniCC GuimarãesFS JocaSRL S-adenosyl-l-methionine antidepressant-like effects involve activation of 5-HT(1A) receptors.Neurochem Int202316210544210.1016/j.neuint.2022.10544236402294
    [Google Scholar]
  66. ZhangK. WangF. ZhaiM. HeM. HuY. FengL. LiY. YangJ. WuC. Hyperactive neuronal autophagy depletes BDNF and impairs adult hippocampal neurogenesis in a corticosterone-induced mouse model of depression.Theranostics20231331059107510.7150/thno.8106736793868
    [Google Scholar]
  67. LiuW. ZhongX. YiY. XieL. ZhouW. CaoW. ChenL. Prophylactic effects of betaine on depression and anxiety behaviors in mice with dextran sulfate sodium-induced colitis.J. Agric. Food Chem.20247238210412105110.1021/acs.jafc.4c0554739276097
    [Google Scholar]
  68. KomotoM. AsadaA. OhshimaY. MiyanagaK. MorimotoH. YasukawaT. MoritoK. TakayamaK. UozumiY. NagasawaK. Dextran sulfate sodium-induced colitis in C57BL/6J mice increases their susceptibility to chronic unpredictable mild stress that induces depressive-like behavior.Life Sci.202228912021710.1016/j.lfs.2021.12021734896162
    [Google Scholar]
  69. BarberioB. ZamaniM. BlackC.J. SavarinoE.V. FordA.C. Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: A systematic review and meta-analysis.Lancet Gastroenterol. Hepatol.20216535937010.1016/S2468‑1253(21)00014‑533721557
    [Google Scholar]
  70. RheeT.G. ShimS.R. ForesterB.P. NierenbergA.A. McIntyreR.S. PapakostasG.I. KrystalJ.H. SanacoraG. WilkinsonS.T. Efficacy and safety of ketamine vs electroconvulsive therapy among patients with major depressive episode.JAMA Psychiatry202279121162117210.1001/jamapsychiatry.2022.335236260324
    [Google Scholar]
  71. LinJ.C. ChanM.H. LeeM.Y. ChenY.C. ChenH.H. N,N-dimethylglycine differentially modulates psychotomimetic and antidepressant-like effects of ketamine in mice.Prog. Neuropsychopharmacol. Biol. Psychiatry20167171310.1016/j.pnpbp.2016.06.00227296677
    [Google Scholar]
  72. LinJ.C. LeeM.Y. ChanM.H. ChenY.C. ChenH.H. Betaine enhances antidepressant-like, but blocks psychotomimetic effects of ketamine in mice.Psychopharmacology2016233173223323510.1007/s00213‑016‑4359‑x27363702
    [Google Scholar]
  73. ChenH. LeeM. Modulatory role for sarcosine, N, N-dimethylglycine and betaine in NMDA receptor activation.Basic Clin Pharmacol Toxicol2014115203
    [Google Scholar]
  74. WeiI.H. ChenK.T. TsaiM.H. WuC.H. LaneH.Y. HuangC.C. Acute amino acid d -serine administration, similar to ketamine, produces antidepressant-like effects through identical mechanisms.J. Agric. Food Chem.20176549107921080310.1021/acs.jafc.7b0421729161812
    [Google Scholar]
  75. YangS.Y. HongC.J. HuangY.H. TsaiS.J. The effects of glycine transporter I inhibitor, N-methylglycine (sarcosine), on ketamine-induced alterations in sensorimotor gating and regional brain c-Fos expression in rats.Neurosci. Lett.2010469112713010.1016/j.neulet.2009.11.05819944746
    [Google Scholar]
  76. HsiaoY.C. LeeM.Y. ChanM.H. ChenH.H. NMDA receptor glycine binding site modulators for prevention and treatment of ketamine use disorder.Pharmaceuticals.16681220233737576010.3390/ph16060812
    [Google Scholar]
  77. ChenS.T. HsiehC.P. LeeM.Y. ChenL.C. HuangC.M. ChenH.H. ChanM.H. Betaine prevents and reverses the behavioral deficits and synaptic dysfunction induced by repeated ketamine exposure in mice.Biomed. Pharmacother.202114411236910.1016/j.biopha.2021.11236934715446
    [Google Scholar]
  78. KofodJ. ElfvingB. NielsenE.H. MorsO. Köhler-ForsbergO. Depression and inflammation: Correlation between changes in inflammatory markers with antidepressant response and long-term prognosis.Eur. Neuropsychopharmacol.20225411612510.1016/j.euroneuro.2021.09.00634598835
    [Google Scholar]
  79. ZhangB. WangP.P. HuK.L. LiL.N. YuX. LuY. ChangH.S. Antidepressant-like effect and mechanism of action of honokiol on the mouse lipopolysaccharide (LPS) depression model.Molecules20192411203510.3390/molecules2411203531141940
    [Google Scholar]
  80. Fusar-PoliL. VozzaL. GabbiadiniA. VanellaA. ConcasI. TinacciS. PetraliaA. SignorelliM.S. AgugliaE. Curcumin for depression: A meta-analysis.Crit. Rev. Food Sci. Nutr.202060152643265310.1080/10408398.2019.165326031423805
    [Google Scholar]
  81. YangW. HuangL. GaoJ. WenS. TaiY. ChenM. HuangZ. LiuR. TangC. LiJ. Betaine attenuates chronic alcohol-induced fatty liver by broadly regulating hepatic lipid metabolism.Mol. Med. Rep.20171645225523410.3892/mmr.2017.729528849079
    [Google Scholar]
  82. LuoQ. HuY. ChenX. LuoY. ChenJ. WangH. Effects of gut microbiota and metabolites on heart failure and its risk factors: A two-sample mendelian randomization study.Front. Nutr.2022989974610.3389/fnut.2022.89974635799593
    [Google Scholar]
  83. AlfthanG. TapaniK. NissinenK. SaarelaJ. AroA. The effect of low doses of betaine on plasma homocysteine in healthy volunteers.Br. J. Nutr.200492466566910.1079/BJN2004125315522136
    [Google Scholar]
  84. YuD.Y. XuZ.R. LiW.F. Effects of betaine on growth performance and carcass characteristics in growing pigs.Asian-Australas. J. Anim. Sci.200417121700170410.5713/ajas.2004.1700
    [Google Scholar]
  85. BarakA.J. BeckenhauerH.C. TumaD.J. Betaine, ethanol, and the liver: A review.Alcohol199613439539810.1016/0741‑8329(96)00030‑48836329
    [Google Scholar]
  86. RenY. ChenZ.Z. SunX.L. DuanH.J. TianJ.S. WangJ.Y. YangH. Metabolomic analysis to detect urinary molecular changes associated with bipolar depression.Neurosci. Lett.202174213551510.1016/j.neulet.2020.13551533227370
    [Google Scholar]
  87. SetoyamaD. KatoT.A. HashimotoR. KunugiH. HattoriK. HayakawaK. Sato-KasaiM. ShimokawaN. KanekoS. YoshidaS. GotoY. YasudaY. YamamoriH. OhgidaniM. SagataN. MiuraD. KangD. KanbaS. Plasma metabolites predict severity of depression and suicidal ideation in psychiatric patients-A multicenter pilot analysis.PLoS One20161112e016526710.1371/journal.pone.016526727984586
    [Google Scholar]
  88. GawandeD. BarewarS. TaksandeJ. UmekarM. GhuleB. TaksandeB. KotagaleN. Achyranthes asperaameliorates stress induced depression in mice by regulating neuroinflammatory cytokines.J. Tradit. Complement. Med.202212654555510.1016/j.jtcme.2022.06.00136325246
    [Google Scholar]
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