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Related Experiment Video

Updated: May 26, 2025

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BDNF/BDNF-AS Gene Polymorphisms Modulate Treatment Response and Remission in Bipolar Disorder: A Randomized Clinical

Anton Shkundin1, Heather E Wheeler2, James Sinacore3

  • 1Department of Psychiatry and Behavioral Neurosciences, Loyola University Chicago, Maywood, IL 60153, USA.

Journal of Personalized Medicine
|February 25, 2025
PubMed
Summary

Genetic variations in Brain-Derived Neurotrophic Factor (BDNF) influence treatment outcomes for bipolar disorder depression. Specific BDNF gene polymorphisms impact response and remission rates when using escitalopram with celecoxib.

Keywords:
bipolar disorderbrain-derived neurotrophic factor (BDNF)celecoxibcyclooxygenase-2 (COX-2)escitalopramrs10835210rs1519480rs6265selective serotonin reuptake inhibitors (SSRIs)treatment-resistant depression

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Bipolar disorder (BD) is a chronic mental health condition linked to treatment resistance, cognitive impairment, and reduced life expectancy.
  • Neuroinflammation and excitotoxicity are implicated in the progression of BD and mood episodes.
  • Brain-Derived Neurotrophic Factor (BDNF) is crucial for neuronal function, and its dysregulation is associated with psychiatric disorders.

Purpose of the Study:

  • To investigate the impact of three BDNF and BDNF-AS gene polymorphisms (rs1519480, rs6265, rs10835210) on treatment outcomes in patients with treatment-resistant bipolar disorder depression (TRBDD).
  • To assess the influence of these genetic variations on serum BDNF levels and treatment response over an eight-week period.

Main Methods:

  • Analysis of 41 participants from a prior randomized clinical trial with available BDNF serum samples and genotype data.
  • Participants diagnosed with bipolar disorder and TRBDD were treated with escitalopram plus placebo or escitalopram plus celecoxib for eight weeks.
  • Statistical methods included mixed ANOVA and chi-square tests to evaluate the association between SNP genotypes and treatment response/remission rates.

Main Results:

  • Non-carriers of the rs6265 A allele and carriers of the rs10835210 A allele showed significantly higher treatment response to adjunctive celecoxib.
  • Remission rates were significantly higher with adjunctive celecoxib compared to escitalopram alone across all three studied SNPs.
  • Specific allele carrier statuses (e.g., rs1519480 G allele non-carriers, rs10835210 A allele non-carriers, rs6265 A allele carriers) were associated with notably higher remission rates.

Conclusions:

  • Genetic variations in BDNF and BDNF-AS genes significantly modulate treatment response and remission rates in patients with bipolar disorder.
  • These findings suggest a potential role for pharmacogenomics in personalizing treatment strategies for TRBDD.
  • Adjunctive celecoxib may offer differential benefits based on specific BDNF gene polymorphisms.