METHYLATION OF METABOTROPIC GLUTAMATE RECEPTORS (MGLUR) IN BRAZILIAN INDIVIDUALS WITH ALCOHOL USE DISORDER

Alcohol use disorder (AUD) is a multifactorial disease, closely related to neurodevelopment, genetic and environmental factors that influence the behavior. Chronic alcohol exposure is associated with enhanced glutamatergic signaling in the brain. Glutamate, the main excitatory neurotransmitter, plays a central role in motivation, reward, affect, learning, memory, and cognitive performance. Persistent glutamatergic overactivation promotes a hyperglutamatergic state, leading to excitotoxic damage and cognitive impairment, which is highly prevalent in individuals with AUD. This preliminary study aimed to investigate the DNA methylation profile of glutamatergic system–related genes, including receptors, enzymes, and transporters, in individuals with AUD. Peripheral blood samples were acquired from recently detoxified patients with AUD (n = 50) and healthy controls (HC; n = 50). Genome-wide DNA methylation was assessed using the Infinium MethylationEPIC BeadChip v2.0, covering over 935,000 CpG sites. After quality control procedures, including assessment of hybridization quality, chip position effects, smoking score, and blood cell composition, we found differential methylation in the metabotropic glutamate receptor 1 gene (GRM1). Previous studies have shown that reduced expression of mGlu receptors can disrupt cognitive processes, particularly learning and memory. In this context, our findings suggest that chronic alcohol consumption–induced glutamatergic imbalance may trigger hypermethylation of GRM1 as a compensatory mechanism to regulate excessive signaling, potentially resulting in cognitive deficits as a secondary effect.