Abnormalities of cyclic adenosine monophosphate signaling in platelets from untreated patients with bipolar disorder

Background: Abnormalities in the cyclic adenosine monophosphate (cAMP)-depe ndent phosphorylation system have been recently reported in patients with b ipolar disorder. We evaluated the immunoreactivity of the regulatory and ca talytic subunits of cAMP-dependent protein kinase (protein kinase A) and 1 of its substrates, Rap 1, in platelets from untreated euthymic, manic, and depressed patients with bipolar disorder and healthy subjects. Methods: Platelets were collected from 112 drug-free patients with bipolar disorder (52 euthymic, 29 depressed, and 31 manic) and 62 healthy subjects. The levels of cAMP-dependent protein kinase and Rap 1 were assessed by Wes tern blot analysis, immunostaining, and computer-assisted imaging. Results: The immunolabeling of the catalytic subunit of cAMP-dependent prot ein kinase was significantly different among groups (P<.001), with higher v alues in untreated depressed and manic patients with bipolar disorder compa red with untreated euthymic patients with bipolar disorder and healthy subj ects. No significant differences were found in the immunolabeling of the re gulatory subunits (type I and type II) of cAMP-dependent protein kinase. Th e immunolabeling of Rap1 was significantly higher (P<.001) in untreated eut hymic, depressed, and manic patients than in healthy persons. Conclusions: Levels of Rapl and the catalytic subunit of cAMP-dependent pro rein kinase are altered in the platelets of bipolar patients. These findin gs may provide clues toward understanding the involvement of cAMP signaling in the pathogenesis of bipolar disorder.