Assessing Causality Between Plasma Brain-Derived Neurotrophic Factor With Major Depression Disorder: A Bidirectional...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Brain-derived neurotrophic factor (BDNF) is implicated in neuronal plasticity and has been explored as a potential biomarker for major depressive disorder (MDD).
• Previous observational studies suggest a link between BDNF and MDD, but causal relationships remain unclear.

Purpose of the Study:

• To investigate the bidirectional causal relationship between plasma BDNF levels and the risk of developing MDD using a two-sample Mendelian randomization (MR) approach.
• To address limitations of prior observational studies by employing genetic variants as instrumental variables.

Main Methods:

• Utilized large-scale Genome-Wide Association Study (GWAS) datasets for MDD and plasma BDNF levels.
• Employed multiple MR methods, including inverse variance weighted (IVW), to assess causality.
• Analyzed data from multiple consortia including the Psychiatric Genomics Consortium, UK Biobank, FinnGen, deCODE, and INTERVAL.

Main Results:

• No significant association was found between genetically predicted plasma BDNF levels and the risk of MDD (IVW OR = 1.00, p = 0.769).
• No evidence of a causal effect of the BDNF gene on MDD was detected (OR = 0.91, p = 0.893).
• Analysis revealed no causal link between MDD and plasma BDNF levels (OR = 0.99, p = 0.783).

Conclusions:

• This MR study provides no evidence for a causal association between plasma BDNF and MDD.
• Findings suggest plasma BDNF may not be a reliable biomarker for MDD.
• Further research is warranted to explore BDNF's functional role in the brain and cerebrospinal fluid in relation to MDD.