The impact of brain-derived neurotrophic factor gene polymorphisms on post-stroke naming in aphasia
Post-stroke aphasia, or language deficits after stroke, afflicts 20-30% of survivors and often persists into the chronic phase. The protein brain-derived neurotrophic factor has been identified as important for neuroplasticity, and is regulated by the brain-derived neurotrophic factor gene. A patient's brain-derived neurotrophic factor genotype may influence their post-stroke aphasia recovery. This study aimed to investigate the impact of a single nucleotide polymorphism in the brain-derived neurotrophic factor gene, rs6265, on language recovery. We hypothesized that individuals with the most common polymorphism would exhibit better chronic naming performance and a more favorable recovery trajectory from poor acute performance to strong chronic outcomes compared to those without the polymorphism. We retrospectively analyzed data from 77 participants with post-stroke aphasia from three recent or ongoing studies that included both repeated standardized picture naming assessments in the acute, subacute, and chronic phases and brain-derived neurotrophic factor genotyping. Statistical analyses controlled for acute performance and lesion volume when evaluating the effect of brain-derived neurotrophic factor genotype on the probability of better chronic language recovery (Aim 1) and on the probability of a person with poor acute performance later having strong performance in the subacute to chronic period (Aim 2). Results indicated that those with the most common polymorphism had a 33% higher likelihood of high naming scores in the chronic phase compared to those with the with less common polymorphisms (with a methionine allele). Individuals with the typical polymorphism whose acute naming was below average after stroke exhibited a 24% higher likelihood of recovering to be above average. Brain-derived neurotrophic factor status was not a significant independent predictor of outcome in either model. Our results suggest that the effect of brain-derived neurotrophic factor polymorphisms on chronic post-stroke aphasia recovery is, at best, modest and underscores the importance of individualized approaches to neurorehabilitation.
Authors
- Julian Bösel (ORCID: https://orcid.org/0000-0001-5428-0771)
- Argye E. Hillis (ORCID: https://orcid.org/0000-0002-5192-1171)
- Victoria Tilton-Bolowsky (ORCID: https://orcid.org/0000-0003-1752-6693)
- Melissa D. Stockbridge (ORCID: https://orcid.org/0000-0001-9069-1236)
- Joseph Kang (ORCID: https://orcid.org/0000-0003-4696-5177)
- Adrian Devine
- Lindsey Kelly (ORCID: https://orcid.org/0000-0003-2053-2912)
- Voss Neal (ORCID: https://orcid.org/0009-0006-5661-5639)
- Matilda Randighieri
Institutions
- Johns Hopkins University (US)
- Heidelberg University (DE)
- Johns Hopkins Medicine (US)
- University Hospital Heidelberg (DE)
- University Medical Centre Mannheim (DE)
- Heidelberg University (US)
Publication Details
- Journal
- PLoS ONE
- Published
- 2025-07-14
- DOI
- https://doi.org/10.1371/journal.pone.0327320
- Primary Topic
- Nerve injury and regeneration
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- NIH Office of the Director
- National Institute on Deafness and Other Communication Disorders