evidence: Imbalanced one carbon metabolism and aberrant autophagy is robustly reported in patients with autism. Polymorphism in the gene methylenetetrahydrofolate reductase (Mthfr), encoding for a key enzyme in this pathway is associated with an increased risk for autistic-spectrum-disorders (ASDs). Autistic-like core and associated behaviors have been described, with contribution of both maternal and offspring Mthfr+/− genotype to the different domains of behavior. Preconception and prenatal supplementation with methyl donor rich diet to human subjects and mice reduced the risk for developing autism and autistic-like behavior, respectively. Here we tested the potential of choline supplementation to Mthfr-deficient mice at young-adulthood to reduce behavioral and neurochemical changes reminiscent of autism characteristics. We show that offspring of Mthfr+/− mothers, whether wildtype or heterozygote, exhibit autistic-like behavior, altered brain p62 protein levels and LC3-II/LC3-I levels ratio, both, autophagy markers. Choline supplementation to adult offspring of Mthfr+/− mothers for 14 days counteracted characteristics related to repetitive behavior and anxiety both in males and in females and improved social behavior solely in male mice. Choline treatment also normalized deviant cortical levels of the autophagy markers measured in male mice. [...] We recently reported that mice heterozygosity of Mthfr-KO causes ASD-like behavior, with a significant contribution of both the offspring and the maternal genotype18. Using a similar phenotyping protocol the possibility to normalize behavior in young adult offspring of Mthfr+/− mothers by choline supplementation was addressed. [...] Goin-Kochel, R. P. et al. The MTHFR 677C–>T polymorphism and behaviors in children with autism: exploratory genotype-phenotype correlations. Autism Res.2, 98–108 (2009).