title: Effects of Lithium Monotherapy for Bipolar Disorder on Gene Expression in Peripheral Lymphocytes.
abstract: BACKGROUND
  This study investigated the effect of lithium monotherapy on peripheral lymphocyte gene expression in bipolar disorder (BD).
  
  
  METHODS
  Twenty-two medication-free bipolar subjects (11 hypomanic, 11 depressed) were started on lithium monotherapy. Closely matched healthy subjects (n = 15) were included as controls but did not receive treatment. Blood RNA samples were collected at baseline and after 2 and 8 weeks of treatment. RNA expression was measured using the Affymetrix GeneChip® Human Gene 1.0 ST Array followed by Ingenuity pathways analysis. The results for the contrast of weeks 2 and 8 were not significantly different and were combined.
  
  
  RESULTS
  In BD subjects, 56 genes showed significant (false discovery rate <0.1) expression changes from baseline; the effect sizes and directions for all of these were similar at weeks 2 and 8. Among these were immune-related genes (IL5RA, MOK, IFI6, and RFX2), purinergic receptors (P2RY14, P2RY2, and ADORA3) and signal transduction-related genes (CAMK1 and PIK3R6). Pathway and upstream regulator analysis also revealed that lithium altered several immune- and signal transduction-related functions. Differentially expressed genes did not correlate with week 8 clinical response, but other genes involved in protein synthesis and degradation did.
  
  
  CONCLUSIONS
  Peripheral gene expression may serve as a biomarker of lithium effect.
authors.affiliation: Center for Behavioral Health, Cleveland Clinic, Cleveland, Ohio, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Ind., USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Anand
authors.affiliation: Department of Biochemistry and Molecular Biology and Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Ind., USA.
authors.forename: Jeanette N
authors.initials: JN
authors.lastname: McClintick
authors.affiliation: Department of Biochemistry and Molecular Biology and Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Ind., USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Murrell
authors.affiliation: Center for Behavioral Health, Cleveland Clinic, Cleveland, Ohio, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Ind., USA.
authors.forename: Harish
authors.initials: H
authors.lastname: Karne
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Ind., USA.
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.affiliation: Department of Biochemistry and Molecular Biology and Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Ind., USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
keywords: Bipolar disorder; Depression; Gene expression; Immune genes; Interferon; Lithium; Mania; Pathway analysis; Signal transduction