POSITRON EMISSION TOMOGRAPHY MEASUREMENT OF CEREBRAL METABOLIC CORRELATES OF YOHIMBINE ADMINISTRATION IN COMBAT-RELATED POSTTRAUMATIC-STRESS-DISORDER

Background: We have previously reported an increase in symptoms of anx iety in patients with posttraumatic stress disorder (PTSD) following a dministration of the beta(2)-antagonist yohimbine, which stimulates br ain norepinephrine release. Preclinical studies show decreased metabol ism in the neocortex and the caudate nucleus with high-dose yohimbine- induced norepinephrine release, but low levels of norepinephrine relea se result in an increase in metabolism in these areas. Methods: We use d positron emission tomography and fludeoxyglucose F 18 to measure bra in metabolism in Vietnam combat veterans with PTSD (n=10) and healthy age-matched control subjects (n=10), following administration of yohim bine (0.4 mg/kg) or placebo in a randomized, double-blind fashion. Res ults: Yohimbine resulted in a significant increase in anxiety in the p atients with PTSD, but not in healthy subjects. There was a significan t difference in brain metabolic response to yohimbine in patients with PTSD compared with healthy subjects in prefrontal, temporal, parietal , and orbitofrontal cortexes. Metabolism tended to decrease in patient s with PTSD and increase in healthy subjects following administration of yohimbine. Conclusion: These findings are consistent with our previ ous hypothesis of enhanced norepinephrine release in the brain with yo himbine in patients with PTSD.