Demonstration of abnormal cyclic AMP production in platelets from patients with fragile X syndrome.

Cyclic AMP production was studied in platelets from 31 patients with fragile X syndrome, 16 patients with mental retardation, 4 patients with autistic disorder, and 57 control individuals. 1-isobutyl-3-methylxanthine (IBMX) was used to inhibit phosphodiesterase; prostaglandin E1 (PGE1), to stimulate cAMP production via a receptor-dependent mechanism, and forskolin (FSK), to directly activate the catalytic subunit. Cyclic AMP production in IBMX, PGE1 + IBMX, and FSK + IBMX was 50% (P < 0.05), 65% (P = 0.001), and 53% (P = 0.001), respectively, in fragile X platelets relative to controls. Cyclic AMP production was not statistically different from controls in patients with mental retardation or autistic disorder. There was no effect of age or sex on cAMP production. Dose response curves suggested that abnormal cAMP production was due to diminished maximal response rather than altered potency of stimulating agents. The data presented here demonstrate that diminished cAMP production exists in platelets from patients with fragile X syndrome. Thus, defective functioning of cAMP-mediated regulatory signalling pathways in fragile X brain may contribute to the mental deficiency in these patients.