COMT and schizophrenia: Nevertheless, multiple lines of evidence indicate that high-activity COMT variants is robustly associated with a greater severity of negative and cognitive symptoms in schizophrenia patients, as well as specific endophenotypic impairments related to functional deficits of the PFC (Egan et al., 2001; Herken and Erdal, 2001; Weinberger et al., 2001; Weinberger, 2002).