title: Higher proportion of inactive Gsk3β in platelets of elderly patients with bipolar disorder: an effect of treatment?
abstract: OBJECTIVE
  It has been postulated that mood stabilizers inhibit glycogen synthase kinase 3-beta (Gsk3β) activity, mainly through its phosphorylation on serine-9 (Ser9). However, in vivo studies addressing Gsk3β activity in patients with bipolar disorder are scarce. Here, we compare Gsk3β inactivation (as indicated by Ser9-phosphorylation) in platelets of elderly patients with bipolar disorder undergoing clinical treatment and healthy elderly adults not taking medication.
  
  
  METHODS
  Platelet samples were obtained from 37 elderly adults (bipolar disorder = 19, controls = 18). Relative changes in Gsk3β inactivation was estimated by comparing the ratios of phosphorylated Gsk3β to total Gsk3β (p-Gsk3β Ser9/Gsk3β) between the disease and control groups.
  
  
  RESULTS
  Phosphorylated-Gsk3β (p < 0.001) and the p-Gsk3β Ser9/Gsk3β ratio (p = 0.006) were elevated in bipolar patients. In the bipolar disorder group, p-Gsk3β Ser9/Gsk3β was positively correlated with serum lithium levels (r = 0.478, p = 0.039).
  
  
  CONCLUSIONS
  Gsk3β inactivation is higher in this group of elderly adults undergoing treatment for bipolar disorder. However, whether the treatment or the disease causes Gsk3β inactivation was confounded by the lack of an unmedicated, bipolar control group and the non-uniform treatment regimens of the bipolar disorder group. Thus, further studies should help distinguish whether Gsk3β inactivation is an effect of drug treatment or an intrinsic characteristic of bipolar disorder.
authors.affiliation: Universidade de São Paulo, School of Medicine, Department and Institute of Psychiatry, Laboratory of Neuroscience, São PauloSP, Brazil.
authors.forename: Rodolfo Braga
authors.initials: RB
authors.lastname: Ladeira
authors.forename: Helena Passarelli Giroud
authors.initials: HP
authors.lastname: Joaquim
authors.forename: Leda Leme
authors.initials: LL
authors.lastname: Talib
authors.forename: Paula Villela
authors.initials: PV
authors.lastname: Nunes
authors.forename: Orestes Vicente
authors.initials: OV
authors.lastname: Forlenza
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000188:drug therapy / Q000201:enzymology*; D001792:Blood Platelets / Q000201:enzymology*; D016022:Case-Control Studies; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000097:blood*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011619:Psychotropic Drugs / Q000627:therapeutic use
chemical_list: D011619:Psychotropic Drugs; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3