PDE4A and fragile X syndrome: Moreover, cAMP itself and the ADCY1-mediated elevation of ERK/PI3K activity may up-regulate certain phosphodiesterases (such as PDE4) (refs 53, 54, 55, but also see ref. 56), which may in turn, as a secondary pathological outcome, counter balance the elevated ADCY1 activity and maintain cAMP homoeostasis in FXS (Fig. 7).