Association between BDNF (Val66Met) Gene Polymorphism, Oxidative Stress Biomarkers and Physiological Alterations in Early and Late Onset Geriatric Depression

<title>Abstract</title> <p>Geriatric depression is a multifactorial psychiatric disorder in which impaired neuroplasticity, oxidative stress and genetic susceptibility may contribute to disease pathogenesis. This study investigated the association of the BDNF rs6265 (Val66Met) polymorphism, serum brain-derived neurotrophic factor (BDNF) levels and oxidative stress biomarkers in North Indian older adults with depression. A hospital-based case control study included 130 patients with geriatric depression (39 early-onset and 91 late-onset) and 130 age and sex matched healthy controls. BDNF rs6265 genotyping was performed using PCR–RFLP, serum BDNF levels were measured by ELISA and oxidative stress biomarkers were estimated using spectrophotometric methods. BDNF rs6265 genotype, allele and genetic model’s analyses showed no significant association (all p &gt; 0.05) with geriatric depression. Serum BDNF concentrations differed significantly among genotypes, with GG carriers exhibiting the highest levels and AA carriers the lowest (p &lt; 0.001). Patients with geriatric depression demonstrated significantly higher lipid peroxidation and glutathione reductase activity than controls (both p &lt; 0.001), whereas catalase, superoxide dismutase and glutathione peroxidase activities showed no significant differences. Although the BDNF rs6265 polymorphism was not associated with geriatric depression, reduced serum BDNF levels and increased oxidative stress were closely related to the disorder. These findings highlight the value of neurotrophic and oxidative stress biomarkers in understanding and clinically evaluating late-life depression.</p>