| Title: | Assessing Causality Between Plasma Brain-Derived Neurotrophic Factor With Major Depression Disorder: A Bidirectional Mendelian Randomization Study |
| Journal: | Brain and Behavior |
| Published: | 18 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40103195/ |
| DOI: | https://doi.org/10.1002/brb3.70425 |
| URL: | https://onlinelibrary.wiley.com/doi/pdf/10.1002/brb3.70425 |
Publication 16002
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Abstract
PURPOSE: This study employed a two-sample Mendelian randomization (MR) approach to investigate the bidirectional relationship between brain-derived neurotrophic factor (BDNF) and major depressive disorder (MDD), addressing gaps left by prior observational studies.</p>
METHODS: We utilized Genome-Wide Association Study (GWAS) datasets, including MDD information from the Psychiatric Genomics Consortium (PGC) and the UK Biobank (N = 500,199), along with plasma BDNF measurements from the FinnGen Consortium (N = 619). In a subsequent phase, we analyzed MDD data from FinnGen (N = 448,069) with plasma BDNF data from three additional GWAS sources: UK Biobank (N = 33,924), deCODE (N = 35,353), and INTERVAL (N = 3301). Multiple MR methods were applied to ensure a robust analysis.</p>
RESULTS: The inverse variance weighted (IVW) method revealed no significant association between plasma BDNF levels and the risk of developing MDD (IVW odds ratio [OR] = 1.00, 95% confidence interval [CI] = 0.99-1.01, p = 0.769). Similarly, no causal effect of the BDNF gene on MDD was identified (OR = 0.91, CI = 0.23-3.56, p = 0.893). Furthermore, there was no evidence supporting a causal link between MDD and plasma BDNF levels (OR = 0.99, CI = 0.89-1.09, p = 0.783). The second phase of analysis confirmed the absence of bidirectional causal relationships.</p>
CONCLUSION: This bidirectional MR analysis provides no evidence of a causal association between plasma BDNF levels and MDD. These findings prompt a re-evaluation of plasma BDNF as a biomarker for MDD and emphasize the need for further investigation into its functional role within the plasma as well as its levels and activity in the brain and cerebrospinal fluid.</p>
10 Keywords
- Adult
- Brain-Derived Neurotrophic Factor
- Depressive Disorder, Major
- Female
- Genome-Wide Association Study
- Humans
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Polymorphism, Single Nucleotide
6 Authors
- Ming Chen
- Hao-Zhang Huang
- Yi-Hui Liu
- Qiang Li
- Lin-Yan Fu
- Cai-Lan Hou
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