Brain-derived neurotrophic factor and stress perception

Abstract

Background

Bipolar disorder (BD) is a severe and chronic mental health condition. Stress is a significant risk factor for BD onset and exacerbation, often triggering depressive symptoms. Perceived stress, reflecting an individual’s subjective experience of stress, is elevated in BD patients. Brain-Derived Neurotrophic Factor (BDNF), crucial for neuronal plasticity and neurotransmitter modulation, decreases under stress conditions. The variation in stress response, with some individuals developing stress-related disorders while others remain resilient, suggests that genetic variations may alter the impact of stress on the risk of psychopathology. The present work was undertaken to investigate the correlations between stress perception (PSS-14) scores and BDNF serum levels and explore their relationship with the minor allele carrier status of specific single nucleotide polymorphisms (SNPs) in patients with treatment-resistant bipolar disorder depression (TRBDD).

Methods

Our cohort included 41 patients diagnosed with BD experiencing treatment resistant depression. Participants, aged 21 to 65, met DSM-IV criteria for BD I or II. Treatment resistance was defined as persistent depression despite adequate antidepressant trials or breakthrough depressive episodes while on a mood stabilizer, an antidepressant and/or an atypical antipsychotic. Patients completed the Perceived Stress Scale-14 (PSS-14) and provided blood samples for BDNF measurement and genotyping. Three SNPs (rs10835210, rs6265, and rs1519480) were selected based on their reported associations with affective disorders. Carriers were identified as individuals with at least one A allele for rs6265, A allele for rs10835210, and G allele for rs1519480.

Results

There was a significant negative Pearson correlation (p = 0.014) between baseline BDNF serum levels and PSS-14 scores. Multiple regression analyses revealed complex patterns involving the SNPs rs10835210, rs6265, and rs1519480. All three SNPs showed a negative correlation between PSS-14 scores and BDNF levels. Both rs10835210 and rs6265 exhibited crossover interactions between carriers and non-carriers at approximately 5 and 10 points, respectively. Additionally, rs6265 demonstrated an inverted directional effect compared to rs10835210 and rs1519480.

Conclusions

Our study highlights a complex relationship between stress, BDNF levels, and BDNF SNPs. The findings suggest two interpretations: perceived stress may reduce BDNF levels, or elevated BDNF levels may protect against stress. The unique roles of these SNPs in modulating BDNF activity are crucial for understanding the biological processes involved in mood disorders and may aid in the implementation of personalized diagnostic and therapeutic interventions.