TY - JOUR
T1 - Abnormalities of cyclic adenosine monophosphate signaling in platelets from untreated patients with bipolar disorder
AU - Perez, Jorge
AU - Tardito, Daniela
AU - Mori, Silvia
AU - Racagni, Giorgio
AU - Smeraldi, Enrico
AU - Zanardi, Raffaella
PY - 1999/3
Y1 - 1999/3
N2 - Background: Abnormalities in the cyclic adenosine monophosphate (cAMP)- dependent phosphorylation system have been recently reported in patients with bipolar disorder. We evaluated the immunoreactivity of the regulatory and catalytic subunits of cAMP-dependent protein kinase (protein kinase A) and 1 of its substrates, Rap1, 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 Rap1 were assessed by Western blot analysis, immunostaining, and computer-assisted imaging. Results: The immunolabeling of the catalytic subunit of cAMP-dependent protein kinase was significantly different among groups (P <.001), with higher values in untreated depressed and manic patients with bipolar disorder compared with untreated euthymic patients with bipolar disorder and healthy subjects. No significant differences were found in the immunolabeling of the regulatory subunits (type I and type II) of cAMP-dependent protein kinase. The immunolabeling of Rap1 was significantly higher (P <.001) in untreated euthymic, depressed, and manic patients than in healthy persons. Conclusions: Levels of Rap1 and the catalytic subunit of cAMP-dependent protein kinase are altered in the platelets of bipolar patients. These findings may provide clues toward understanding the involvement of cAMP signaling in the pathogenesis of bipolar disorder.
AB - Background: Abnormalities in the cyclic adenosine monophosphate (cAMP)- dependent phosphorylation system have been recently reported in patients with bipolar disorder. We evaluated the immunoreactivity of the regulatory and catalytic subunits of cAMP-dependent protein kinase (protein kinase A) and 1 of its substrates, Rap1, 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 Rap1 were assessed by Western blot analysis, immunostaining, and computer-assisted imaging. Results: The immunolabeling of the catalytic subunit of cAMP-dependent protein kinase was significantly different among groups (P <.001), with higher values in untreated depressed and manic patients with bipolar disorder compared with untreated euthymic patients with bipolar disorder and healthy subjects. No significant differences were found in the immunolabeling of the regulatory subunits (type I and type II) of cAMP-dependent protein kinase. The immunolabeling of Rap1 was significantly higher (P <.001) in untreated euthymic, depressed, and manic patients than in healthy persons. Conclusions: Levels of Rap1 and the catalytic subunit of cAMP-dependent protein kinase are altered in the platelets of bipolar patients. These findings may provide clues toward understanding the involvement of cAMP signaling in the pathogenesis of bipolar disorder.
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M3 - Article
C2 - 10078502
AN - SCOPUS:0033019227
VL - 56
SP - 248
EP - 253
JO - Archives of General Psychiatry
JF - Archives of General Psychiatry
SN - 0003-990X
IS - 3
ER -