Veterans with alcohol use disorder carrying the BDNF Met allele showed accelerated age-related decline in a brain health marker (NAA) in the prefrontal cortex, and had higher rates of cannabis use disorder and depression.
Read this if you are interested in genetic risk factors for brain damage from substance use or in personalized approaches to addiction treatment.
BDNF Met carriersShowed markedly steeper age-related brain metabolite decline in prefrontal cortex
What the researchers found
Among 95 veterans with alcohol use disorder, those carrying the BDNF rs6265 Met variant (n=35) showed markedly greater age-related decline in NAA/Cr levels in the left dorsolateral prefrontal cortex compared to Val/Val homozygotes (n=60). While mean metabolite levels did not differ between groups, the trajectory of decline with age was steeper in Met carriers. Met carriers also had higher rates of major depression history and cannabis use disorder in the 12 months prior to the study.
Why it matters
The BDNF gene influences brain repair and plasticity. This study suggests that a common genetic variant may make some people with alcohol use disorder more vulnerable to brain aging, and that this same variant clusters with cannabis use disorder and depression — potentially identifying a high-risk subgroup.
The numbers in context
- 95 veterans with AUD (mean age 46±12 years, range 25-71)
- Val/Met carriers: n=35; Val/Val: n=60
- Val/Met showed greater age-related NAA/Cr decline in left DLPFC
- Val/Met had higher frequency of MDD history
- Val/Met had higher frequency of cannabis use disorder
- MRS at 3 Tesla
How the study worked
Cross-sectional study of veterans from VA Palo Alto residential treatment centers. Single voxel magnetic resonance spectroscopy (MRS) at 3 Tesla measured NAA, choline, and creatine in left dorsolateral prefrontal cortex. Metabolite ratios compared between BDNF genotype groups.
Who was studied
95 veterans with alcohol use disorder from VA Palo Alto residential treatment centers
What this study cannot tell us
Cross-sectional design infers age-related decline from age variation, not longitudinal follow-up. Relatively small sample. All participants were veterans in residential treatment, limiting generalizability. Multiple comparisons not fully addressed.
How to read the evidence
Cross-sectional neuroimaging genetics study in a specific veteran population. Novel findings but limited by design and sample size.
When this study was published
Published in 2023. Represents growing interest in pharmacogenomics of addiction treatment.
The bigger picture
Identifying genetic moderators of brain damage in substance use disorders could lead to personalized treatment approaches. If BDNF Met carriers are more vulnerable to prefrontal decline, they might benefit from different or more intensive interventions.
Questions still open
- Does the BDNF Met allele similarly accelerate brain aging in cannabis use disorder independent of alcohol?
- Could BDNF-targeted interventions (exercise, specific therapies) be especially beneficial for Met carriers?
- Would non-invasive brain stimulation of the left DLPFC be more or less effective in Met carriers?
Read the original research
BDNF rs6265 Met carriers with alcohol use disorder show greater age-related decline of N-acetylaspartate in left dorsolateral prefrontal cortex.
Drug and alcohol dependence, 248, 109901
Citation
Durazzo, Timothy C; McNerney, M Windy; Hansen, Annika M; Gu, Meng; Sacchet, Matthew D; Padula, Claudia B. (2023). BDNF rs6265 Met carriers with alcohol use disorder show greater age-related decline of N-acetylaspartate in left dorsolateral prefrontal cortex.. Drug and alcohol dependence, 248, 109901. https://doi.org/10.1016/j.drugalcdep.2023.109901