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. 2025;21(4):13-20. doi: 10.2174/0115733998274778231218145449.

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. vs. 122± 17.47, P< 0.001). There was a statistically significant difference in BDNF levels in patients with diabetes among the three genotypes of the BDNF gene (P-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 (p = 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. Multicenter studies with more participants are required.

Keywords: Brain-derived neurotrophic factor; depression; depressive disorder.; diabetes mellitus; nerve growth factors; type 2.

MeSH terms

  • Adult
  • Aged
  • Brain-Derived Neurotrophic Factor* / blood
  • Brain-Derived Neurotrophic Factor* / genetics
  • Case-Control Studies
  • Depression* / blood
  • Depression* / genetics
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / genetics
  • Diabetes Mellitus, Type 2* / psychology
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Risk Factors

Substances

  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human