Support for the influence of estrogens (and perhaps other sex hormones) on the (gender specific) effects of the COMT Val158Met polymorphism also comes from a study, which showed that genetic variation in the COMT gene associated with extreme COMT enzyme reduction [22q11DS patients (only one copy of the COMT gene) carrying the Met allele in the COMTVal158Met polymorphism], was associated with cortical thinning only in females and only after puberty (similar effect also found in genetically modified mice; Sannino et al., 2017). The gene discussed is COMT; the disease is 22q11.2 deletion syndrome.