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Cyclic adenosine 3',5'-monophosphate (cAMP) signal transduction was examined in lymphocytes and platelets obtained from patients with posttraumatic stress disorder. Intact lymphocytes from the posttraumatic patients (N = 10) showed significantly lower basal, isoproterenol-, and forskolin-stimulated cAMP levels than those from 10 healthy control subjects. In platelet membrane preparations, basal, forskolin-, aluminum chloride plus sodium fluoride-, and prostaglandin E1-stimulated adenylate cyclase activity levels were all significantly lower in the posttraumatic group than in the control group. The authors discuss the potential role of their findings as a biological marker for posttraumatic stress disorder.

Reliability of measurement of lymphocyte cyclic AMP synthesis in intact cells was estimated by taking 3 successive blood samples during a one-month period from 11 healthy volunteers. Isoproterenol and prostaglandin E1-stimulated cyclic AMP accumulation were used to evaluate the activity of these two receptor activities in human lymphocytes. Forskolin-stimulated cyclic AMP accumulation was used to evaluate the activity of the Ns/catalytic subunit. Only for forskolin was significant reliability observed. For isoproterenol and prostaglandin E1 significant reliability was observed only for male subjects.

Beta-adrenergic-mediated cyclic AMP accumulation was reduced in lymphocytes obtained from depressed patients from that observed in an age- and sex-matched group of control subjects. Among the depressed patients, those not responding to treatment showed significantly lower pretreatment responses to isoproterenol compared with patients who exhibited significant clinical improvement during antidepressant treatment. Late-night (terminal) insomnia was significantly associated with the blunted response to beta-adrenergic stimulation. In depressed patients with the lowest isoproterenol response, the effect of forskolin (which acts distal to the receptor and directly stimulates the catalytic subunit) on cyclic AMP accumulation was also significantly decreased. This suggests that post-receptor modulations of signal amplification also play a role in the reduced response to beta-adrenergic stimulation in depression.