Association
between low levels of platelet adenylyl cyclase
activity and an increased risk of major
depression
Because
major depression is a complex and heterogeneous
disorder difficult to diagnose and to treat, the
identification of state or trait markers for
major depression would facilitate more effective
prevention and treatment strategies. Adenylyl
cyclase is an enzyme that converts adenosine
5'-triphosphate (ATP) to the intracellular
second messenger, cyclic
adenosine-3',5'-monophosphate (cAMP). Some
studies have suggested lower levels of adenylyl
cyclase activity in platelets of depressed
patients. A study evaluated the relationship
between platelet adenylyl cyclase activity and
major depression.
The World Health Organization and the
International Society on Biomedical Research on
Alcoholism conducted a multi-center,
international, cross-sectional study with 1481
participants (226 subjects with a lifetime
diagnosis of major depression and 1255 control
subjects). Basal, cesium fluoride- stimulated,
forskolin-stimulated, and Gpp(NH)p-stimulated
adenylyl cyclase activity was measured.
After excluding all recent users of addictive
drugs, analgesics, or antidepressants, subjects
in the lowest quartile for all measurements of
adenylyl cyclase activity had a significantly
increased risk of major depression. After
adjusting for the covariates, the odds ratios
for major depression, comparing the bottom and
top quartiles of adenylyl cyclase activity, were
2.69 for basal, 3.72 for cesium
fluoride-stimulated, 6.20 for
forskolin-stimulated, and 2.20 for
Gpp(NH)p-stimulated. However, the association
between all measures of platelet adenylyl
cyclase activity and the increased risk for
depression is markedly attenuated by recent drug
use.
These findings confirm that levels of platelet
adenylyl cyclase activity are associated with an
increased risk of major depression, as suggested
by previous studies. The level adenylyl cyclase
activity could be a good candidate for a state
or trait marker of major depression and may
prove to be useful as a prognostic or diagnostic
tool for major depression. Hines
LM, Tabakoff B; WHO/ISBRA Study on State and
Trait Markers of Alcohol Use and Dependence
Investigators. Platelet adenylyl cyclase
activity: a biological marker for major
depression and recent drug use. Biol Psychiatry
2005, 58:955-962.