Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Diabetes Reviews
  4. Volume 21, Issue 4
  5. Article
Volume 21, Issue 4
  • ISSN: 1573-3998
  • E-ISSN: 1875-6417

Abstract

Background

Diabetes mellitus and depression are comorbidities that can be caused by each other. Brain-derived neurotrophic factor (BDNF) functions as a neuronal growth factor. It maintains the functional integrity of the nervous system.

Aim

To study the possible association between BDNF levels and gene polymorphism with depression in patients diagnosed with type 2 diabetes mellitus.

Methods

The Elisa technique measured BDNF, and rs6265 gene polymorphism was detected using real-time PCR. Depression was assessed utilizing a clinical interview tool designed to establish the diagnosis of depression and differentiate it from other psychiatric diseases.

Results

BDNF levels were significantly lower in patients with type 2 diabetes mellitus and symptoms of depression than in patients with type 2 diabetes mellitus and no symptoms of depression (82.6±16.1. 122± 17.47, There was a statistically significant difference in BDNF levels in patients with diabetes among the three genotypes of the BDNF gene (-value < 0.001). Val/ Val carriers had the highest serum BDNF levels, and Met/ Met carriers had the lowest serum BDNF levels. Subgroup analysis showed statistically significant genotype-related differences in serum BDNF levels among the three subgroups in the Depression group. Val/ Val carriers had the highest serum BDNF levels, and Met/ Met carriers had the lowest serum BDNF levels. BDNF Val66Met polymorphism had no significant association with the presence of depression, yet there was a trend towards significance ( = 0.05).

Conclusion

In this pilot, Low levels of BDNF were associated with depression in patients with type 2 diabetes. Carriers of the Met/ Met allele have the lowest serum BDNF levels. Multi-center studies with more participants are required.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdr/10.2174/0115733998274778231218145449
2024-01-08
2025-03-07

  • From This Site

    /content/journals/cdr/10.2174/0115733998274778231218145449
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Diagnostic and statistical manual of mental disorders: DSM-5™American Psychiatric Association.2013
  2. GhandourA.A. Out of pocket expenditure on non-communicable diseases among egyptian patients.Egypt. J. Hosp. Med.201558556210.12816/0009361
     [Google Scholar]
  3. GoldenS.H. LazoM. CarnethonM. BertoniA.G. SchreinerP.J. Diez RouxA.V. LeeH.B. LyketsosC. Examining a bidirectional association between depressive symptoms and diabetes.JAMA2008299232751275910.1001/jama.299.23.275118560002
     [Google Scholar]
  4. MezukB. EatonW.W. AlbrechtS. GoldenS.H. Depression and type 2 diabetes over the lifespan: A meta-analysis.Diabetes Care200831122383239010.2337/dc08‑098519033418
     [Google Scholar]
  5. RotellaF. MannucciE. Depression as a risk factor for diabetes: A meta-analysis of longitudinal studies.J. Clin. Psychiatry2013741313710.4088/JCP.12r0792223419223
     [Google Scholar]
  6. NouwenA. WinkleyK. TwiskJ. LloydC.E. PeyrotM. IsmailK. PouwerF. Type 2 diabetes mellitus as a risk factor for the onset of depression: A systematic review and meta-analysis.Diabetologia201053122480248610.1007/s00125‑010‑1874‑x20711716
     [Google Scholar]
  7. AikensJ.E. PerkinsD.W. LiptonB. PietteJ.D. Longitudinal analysis of depressive symptoms and glycemic control in type 2 diabetes.Diabetes Care20093271177118110.2337/dc09‑007119389814
     [Google Scholar]
  8. HamiltonM. A rating scale for depression.J. Neurol. Neurosurg. Psychiatry1960231566210.1136/jnnp.23.1.5614399272
     [Google Scholar]
  9. BathK.G. LeeF.S. Variant BDNF (Val66Met) impact on brain structure and function.Cogn. Affect. Behav. Neurosci.200661798510.3758/CABN.6.1.7916869232
     [Google Scholar]
  10. RauskolbS. ZagrebelskyM. DreznjakA. DeograciasR. MatsumotoT. WieseS. ErneB. SendtnerM. Schaeren-WiemersN. KorteM. BardeY.A. Global deprivation of brain-derived neurotrophic factor in the CNS reveals an area-specific requirement for dendritic growth.J. Neurosci.20103051739174910.1523/JNEUROSCI.5100‑09.201020130183
     [Google Scholar]
  11. PruunsildP. KazantsevaA. AidT. PalmK. TimmuskT. Dissecting the human BDNF locus: Bidirectional transcription, complex splicing, and multiple promoters.Genomics200790339740610.1016/j.ygeno.2007.05.00417629449
     [Google Scholar]
  12. Lima GiacobboB. DoorduinJ. KleinH.C. DierckxR.A.J.O. BrombergE. de VriesE.F.J. Brain-derived neurotrophic factor in brain disorders: Focus on neuroinflammation.Mol. Neurobiol.20195653295331210.1007/s12035‑018‑1283‑630117106
     [Google Scholar]
  13. EganM.F. KojimaM. CallicottJ.H. GoldbergT.E. KolachanaB.S. BertolinoA. ZaitsevE. GoldB. GoldmanD. DeanM. LuB. WeinbergerD.R. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function.Cell2003112225726910.1016/S0092‑8674(03)00035‑712553913
     [Google Scholar]
  14. SartoriusA. HellwegR. LitzkeJ. VogtM. DormannC. VollmayrB. Danker-HopfeH. GassP. Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats.Pharmacopsychiatry200942627027610.1055/s‑0029‑122416219924587
     [Google Scholar]
  15. ShenT. YouY. JosephC. MirzaeiM. KlistornerA. GrahamS.L. GuptaV. BDNF polymorphism: A review of its diagnostic and clinical relevance in neurodegenerative disorders.Aging Dis.20189352353610.14336/AD.2017.071729896439
     [Google Scholar]
  16. ZhouJ.X. LiH.C. BaiX.J. ChangB.C. LiC.J. SunP. ChenL.M. Functional Val66Met polymorphism of Brain-derived neurotrophic factor in type 2 diabetes with depression in Han Chinese subjects.Behav. Brain Funct.201391343410.1186/1744‑9081‑9‑3423968401
     [Google Scholar]
  17. VentrigliaM. Bocchio ChiavettoL. BenussiL. BinettiG. ZanettiO. RivaM.A. GennarelliM. Association between the BDNF 196 A/G polymorphism and sporadic Alzheimer’s disease.Mol. Psychiatry20027213613710.1038/sj.mp.400095211840305
     [Google Scholar]
  18. KüppersE. BeyerC. Dopamine regulates brain-derived neurotrophic factor (BDNF) expression in cultured embryonic mouse striatal cells.Neuroreport20011261175117910.1097/00001756‑200105080‑0002511338187
     [Google Scholar]
  19. HorchH.W. KatzL.C. BDNF release from single cells elicits local dendritic growth in nearby neurons.Nat. Neurosci.20025111177118410.1038/nn92712368805
     [Google Scholar]
  20. HymanC. HoferM. BardeY.A. JuhaszM. YancopoulosG.D. SquintoS.P. LindsayR.M. BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra.Nature1991350631523023210.1038/350230a02005978
     [Google Scholar]
  21. KleinA.B. WilliamsonR. SantiniM.A. ClemmensenC. EttrupA. RiosM. KnudsenG.M. AznarS. Blood BDNF concentrations reflect brain-tissue BDNF levels across species.Int. J. Neuropsychopharmacol.201114334735310.1017/S146114571000073820604989
     [Google Scholar]
  22. American Diabetes Association2. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2021.Diabetes Care202144Suppl. 1S15S3310.2337/dc21‑S00233298413
     [Google Scholar]
  23. Chacon-CortesD. HauptL.M. LeaR.A. GriffithsL.R. Comparison of genomic DNA extraction techniques from whole blood samples: A time, cost and quality evaluation study.Mol. Biol. Rep.20123955961596610.1007/s11033‑011‑1408‑822228086
     [Google Scholar]
  24. ChanY.H. Biostatistics 103: Qualitative data - tests of independence.Singapore Med. J.2003441049850315024452
     [Google Scholar]
  25. ChanY.H. Biostatistics 104: Correlational analysis.Singapore Med. J.2003441261461914770254
     [Google Scholar]
  26. HegaziR. El-GamalM. Abdel-HadyN. HamdyO. Epidemiology of and risk factors for type 2 diabetes in egypt.Ann. Glob. Health201681681482010.1016/j.aogh.2015.12.01127108148
     [Google Scholar]
  27. NanayakkaraN. PeaseA. RanasinhaS. WischerN. AndrikopoulosS. SpeightJ. de CourtenB. ZoungasS. Depression and diabetes distress in adults with type 2 diabetes: Results from the Australian National Diabetes Audit (ANDA) 2016.Sci. Rep.201881784610.1038/s41598‑018‑26138‑529777153
     [Google Scholar]
  28. de GrootM. AndersonR. FreedlandK.E. ClouseR.E. LustmanP.J. Association of depression and diabetes complications: A meta-analysis.Psychosom. Med.200163461963010.1097/00006842‑200107000‑0001511485116
     [Google Scholar]
  29. HeraclidesA. ChandolaT. WitteD.R. BrunnerE.J. Psychosocial stress at work doubles the risk of type 2 diabetes in middle-aged women: Evidence from the Whitehall II study.Diabetes Care200932122230223510.2337/dc09‑013219720842
     [Google Scholar]
  30. LustmanP.J. ClouseR.E. Depression in diabetic patients: The relationship between mood and glycemic control.J. Diabetes Complications200519211312215745842
     [Google Scholar]
  31. BădescuS.V. TătaruC. KobylinskaL. GeorgescuE.L. ZahiuD.M. ZăgreanA.M. ZăgreanL. The association between Diabetes mellitus and Depression.J. Med. Life20169212012527453739
     [Google Scholar]
  32. KreiderK.E. Diabetes distress or major depressive disorder? A practical approach to diagnosing and treating psychological comorbidities of diabetes.Diabetes Ther.2017811710.1007/s13300‑017‑0231‑128160185
     [Google Scholar]
  33. KhalediM. HaghighatdoostF. FeiziA. AminorroayaA. The prevalence of comorbid depression in patients with type 2 diabetes: An updated systematic review and meta-analysis on huge number of observational studies.Acta Diabetol.201956663165010.1007/s00592‑019‑01295‑930903433
     [Google Scholar]
  34. KatonW.J. RussoJ.E. HeckbertS.R. LinE.H.B. CiechanowskiP. LudmanE. YoungB. Von KorffM. The relationship between changes in depression symptoms and changes in health risk behaviors in patients with diabetes.Int. J. Geriatr. Psychiatry201025546647510.1002/gps.236319711303
     [Google Scholar]
  35. MoultonC.D. PickupJ.C. IsmailK. The link between depression and diabetes: The search for shared mechanisms.Lancet Diabetes Endocrinol.20153646147110.1016/S2213‑8587(15)00134‑525995124
     [Google Scholar]
  36. MondalA.C. FatimaM. Direct and indirect evidences of BDNF and NGF as key modulators in depression: Role of antidepressants treatment.Int. J. Neurosci.2019129328329610.1080/00207454.2018.152732830235967
     [Google Scholar]
  37. LealG. AfonsoP.M. SalazarI.L. DuarteC.B. Regulation of hippocampal synaptic plasticity by BDNF.Brain Res.201516218210110.1016/j.brainres.2014.10.01925451089
     [Google Scholar]
  38. OzanE. OkurH. EkerÇ. EkerÖ.D. GönülA.S. AkarsuN. The effect of depression, BDNF gene val66met polymorphism and gender on serum BDNF levels.Brain Res. Bull.2010811616510.1016/j.brainresbull.2009.06.02219589373
     [Google Scholar]
  39. SharifS. RazaM.T. MushtaqS. AfreenB. HashmiB.A. AliM.H. Frequency of depression in patients with type 2 diabetes mellitus and its relationship with glycemic control and diabetic microvascular complications.Cureus2019117e514510.7759/cureus.514531523573
     [Google Scholar]
  40. GaryT.L. CrumR.M. Cooper-PatrickL. FordD. BrancatiF.L. Depressive symptoms and metabolic control in African-Americans with type 2 diabetes.Diabetes Care2000231232910.2337/diacare.23.1.2310857963
     [Google Scholar]
  41. WeiY.G. CaiD.B. LiuJ. LiuR.X. WangS.B. TangY.Q. ZhengW. WangF. Cholesterol and triglyceride levels in first-episode patients with major depressive disorder: A meta-analysis of case-control studies.J. Affect. Disord.202026646547210.1016/j.jad.2020.01.11432056914
     [Google Scholar]
  42. SuwaM. KishimotoH. NofujiY. NakanoH. SasakiH. RadakZ. KumagaiS. Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus.Metabolism200655785285710.1016/j.metabol.2006.02.01216784955
     [Google Scholar]
  43. LiB. LangN. ChengZ.F. Serum Levels of brain-derived neurotrophic factor are associated with diabetes risk, complications, and obesity: A cohort study from chinese patients with type 2 diabetes.Mol. Neurobiol.20165385492549910.1007/s12035‑015‑9461‑226454822
     [Google Scholar]
  44. SandriniL. Di MinnoA. AmadioP. IeraciA. TremoliE. BarbieriS. Association between obesity and circulating Brain-Derived Neurotrophic Factor (BDNF) levels: Systematic review of literature and meta-analysis.Int. J. Mol. Sci.2018198228110.3390/ijms1908228130081509
     [Google Scholar]
  45. PrabuP. PoongothaiS. ShanthiraniC.S. AnjanaR.M. MohanV. BalasubramanyamM. Altered circulatory levels of miR-128, BDNF, cortisol and shortened telomeres in patients with type 2 diabetes and depression.Acta Diabetol.202057779980710.1007/s00592‑020‑01486‑932025863
     [Google Scholar]
  46. YoussefM.M. UnderwoodM.D. HuangY.Y. HsiungS. LiuY. SimpsonN.R. BakalianM.J. RosoklijaG.B. DworkA.J. ArangoV. MannJ.J. Association of BDNF Val66Met polymorphism and brain BDNF levels with major depression and suicide.Int. J. Neuropsychopharmacol.201821652853810.1093/ijnp/pyy00829432620
     [Google Scholar]
  47. PeiY. SmithA.K. WangY. PanY. YangJ. ChenQ. PanW. BaoF. ZhaoL. TieC. WangY. WangJ. ZhenW. ZhouJ. MaX. The brain‐derived neurotrophic‐factor ( BDNF ) val66met polymorphism is associated with geriatric depression: A meta‐analysis.Am. J. Med. Genet. B. Neuropsychiatr. Genet.2012159B556056610.1002/ajmg.b.3206222610920
     [Google Scholar]
  48. YoshimuraR. KishiT. SuzukiA. Umene-NakanoW. Ikenouchi-SugitaA. HoriH. OtaniK. IwataN. NakamuraJ. The brain-derived neurotrophic factor (BDNF) polymorphism Val66Met is associated with neither serum BDNF level nor response to selective serotonin reuptake inhibitors in depressed Japanese patients.Prog. Neuropsychopharmacol. Biol. Psychiatry20113541022102510.1016/j.pnpbp.2011.02.00921338649
     [Google Scholar]
  49. VerhagenM. van der MeijA. van DeurzenP A M. JanzingJ.G.E. Arias-VásquezA. BuitelaarJ.K. FrankeB. Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity.Mol. Psychiatry201015326027110.1038/mp.2008.10918852698
     [Google Scholar]
/content/journals/cdr/10.2174/0115733998274778231218145449
Loading
Brain-derived Neurotrophic Factor Level and Gene Polymorphism as Risk Factors for Depression in Patients with type 2 Diabetes Mellitus- A Case-Controlled Study
Curr. Diabetes Rev. 21, E080124225344 (2025); https://doi.org/10.2174/0115733998274778231218145449
/content/journals/cdr/10.2174/0115733998274778231218145449
/content/journals/cdr/10.2174/0115733998274778231218145449
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Brain-derived neurotrophic factor; depression; depressive disorder; diabetes mellitus; nerve growth factors; type 2

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test