Absence of reduced platelet adenylate cyclase activity in Vietnam veterans with PTSD

Abstract

Many studies have been devoted to an examination of radioligand receptor binding and postreceptor signal transduction in peripheral cells obtained from patients suffering from mood or anxiety disorders. Postreceptor signal transduction has been investigated by the use of agents that interact with the adenylate cyclase system at points distal to the receptor, such as aluminum chloride (AIC13) and sodium fluoride (NaF), which affect the guanyl nucleotidebinding (G) protein, and forskolin, which affects the catalytic (C) unit of the enzyme. Post-traumatic stress disorder (PTSD) is a member of the group of anxiety disorders which also includes generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder. PTSD also shares phenomenological features with depression (Sierles et al 1983). Abnormalities in adenylate cyclase activity have been demonstrated in peripheral cells derived both from panic disorder patients (Charney et al 1989) and depressed patients (Ebstein et a11988; Kanof et al 1988). Recent evidence has indicated possible abnormalities at both the receptor and postreeeptor levels in platelets from PTSD patients. Perry et al (1987) found a reduction in alpha-2-adrenergic receptors in 11 Vietnam veterans with PTSD relative to agematched normal controls. This was due to a relative loss of sites labeled with low affinity by the antagonist 3H-rauwolscine, representing those sites coupled via the inhibitory G protein Gi to adenylate cyclase. The involvement of adrenergic receptors in PTSD has been recently reviewed (Lerer et al 1994). In a series of studies, our laboratory has investigated platelet adenylate cyclase in PTSD with mixed results. A first study (Lerer