PAH also requires the cofactor BH4 for optimal activity and inflammatory cytokines such as interferon-γ (the levels of which have been reported to be elevated in schizophrenia [28]) stimulate GTPCH-1, the first enzyme involved in the synthesis of BH4; however, due to the relative deficiency of an intermediate enzyme, 6-pyruvoyltetrahydropterin synthase, there is reduced BH4 synthesis in immune-activated states [29]. Here, GCH1 is linked to schizophrenia.