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Positron Emission Tomography Measurement of Cerebral Metabolic Correlates of Yohimbine Administration in Combat-Related Posttraumatic Stress Disorder
J. Douglas Bremner, MD;
Robert B. Innis, MD, PhD;
Chin K. Ng, PhD;
Lawrence H. Staib, PhD;
Ronald M. Salomon, MD;
Richard A. Bronen, MD;
James Duncan, PhD;
Steven M. Southwick, MD;
John H. Krystal, MD;
Dayton Rich;
George Zubal, PhD;
Holley Dey, MD;
Robert Soufer, MD;
Dennis S. Charney, MD
Arch Gen Psychiatry. 1997;54(3):246-254.
Abstract
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Background
We have previously reported an increase in symptoms of anxiety in patients with posttraumatic stress disorder (PTSD) following administration of the β2-antagonist yohimbine, which stimulates brain norepinephrine release. Preclinical studies show decreased metabolism in the neocortex and the caudate nucleus with high-dose yohimbine-induced norepinephrine release, but low levels of norepinephrine release result in an increase in metabolism in these areas.
Methods
We used positron emission tomography and fludeoxyglucose F 18 to measure brain metabolism in Vietnam combat veterans with PTSD (n=10) and healthy age-matched control subjects (n=10), following administration of yohimbine (0.4 mg/kg) or placebo in a randomized, double-blind fashion.
Results
Yohimbine resulted in a significant increase in anxiety in the patients with PTSD, but not in healthy subjects. There was a significant 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 patients with PTSD and increase in healthy subjects following administration of yohimbine.
Conclusion
These findings are consistent with our previous hypothesis of enhanced norepinephrine release in the brain with yohimbine in patients with PTSD.
Author Affiliations
From the Departments of Psychiatry (Drs Bremner, Innis, Salomon, Southwick, Krystal, and Charney) and Diagnostic Radiology (Drs Bremner, Ng, Staib, Bronen, Duncan, Zubal, Dey, and Soufer), Yale University School of Medicine, New Haven, Conn; and the National Center for Posttraumatic Stress Disorder (Drs Bremner, Innis, Southwick, Krystal, and Charney), West Haven Veterans Affairs Medical Center (Drs Bremner, Innis, Ng, Salomon, Southwick, Krystal, Dey, Soufer, and Charney and Mr Rich), and the Yale/Veterans Affairs Positron Emission Tomography Center (Drs Ng, Dey, and Soufer and Mr Rich), West Haven, Conn.
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