Original article| Volume 58, ISSUE 12, P955-962, December 15, 2005

Platelet Adenylyl Cyclase Activity: A Biological Marker for Major Depression and Recent Drug Use

  • Lisa M. Hines
    Address reprint requests to Lisa M. Hines, Sc.D., University of Colorado Health Sciences Center at Fitzsimons, School of Medicine, Department of Pharmacology, Mail Stop F-8303, P.O. Box 6511, Aurora, CO 80045-0511.
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado.
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  • Boris Tabakoff
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado.
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  • WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence Investigators


      Adenylyl cyclase (AC) is an enzyme that can regulate the physiologic effects of numerous drugs and hormones through the production of cyclic adenosine-3′,5′-monophosphate (cAMP). Some studies suggest that certain measures of AC activity are lower among depressed subjects. We examined the relationship between various measures of AC activity and major depression, taking into account potential confounders, such as drug use and gender.


      We assessed the relationship between platelet levels of AC activity and lifetime diagnosis of major depression among 1481 participants (226 subjects with a history of major depression and 1255 control subjects) in an international, cross-sectional study initiated by the World Health Organization and the International Society on Biomedical Research on Alcoholism.


      After accounting for recent drug use, subjects with a history of major depression had markedly lower mean levels for all measures of platelet AC activity compared with control subjects. The adjusted odds ratios for major depression comparing the bottom to the top quartile of AC activity were 2.69 for basal (95% confidence interval [CI] 1.30–5.56), 3.72 for cesium fluoride-stimulated (95% CI 1.54–8.98), 6.20 for forskolin-stimulated (95% CI 2.04–18.80), and 2.20 for Gpp(NH)p-stimulated (95% CI 1.03–4.70).


      Subjects with major depression have lower platelet AC activity levels, and this relationship is dramatically attenuated by various types of drug use.

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