OBJECTIVE: Lithium remains a first-line treatment for bipolar disorder, but the mechanisms by which it prevents the recurrence of mood episodes are not known. The authors utilized data from a genomewide association study to examine associations between single nucleotide polymorphisms (SNPs) and the outcome of lithium treatment in two cohorts of patients with bipolar I disorder or bipolar II disorder. METHOD: The hazard for mood episode recurrence was examined among 1,177 patients with bipolar I disorder or bipolar II disorder, including 458 individuals treated with lithium carbonate or citrate, who were participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) cohort. SNPs showing the greatest evidence of association in Cox regression models were then examined for association with positive lithium response among 359 bipolar I or II disorder patients treated with lithium carbonate or citrate in a second cohort from the University College London. RESULTS: The strongest association in the STEP-BD cohort (minimum p=5.5 x 10(-7)) was identified for a region on chromosome 10p15 (rs10795189). Of the regions showing suggestive evidence (p<5 x 10(-4)) of association with lithium response, five were further associated with positive lithium response in the University College London cohort, including SNPs in a region on chromosome 4q32 spanning a gene coding for the glutamate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) receptor GRIA2. CONCLUSIONS: Multiple novel loci merit further examination for association with lithium response in bipolar disorder patients, including one region that spans the GRIA2 gene, for which expression has been shown to be regulated by lithium treatment.
OBJECTIVE:Lithium remains a first-line treatment for bipolar disorder, but the mechanisms by which it prevents the recurrence of mood episodes are not known. The authors utilized data from a genomewide association study to examine associations between single nucleotide polymorphisms (SNPs) and the outcome of lithium treatment in two cohorts of patients with bipolar I disorder or bipolar II disorder. METHOD: The hazard for mood episode recurrence was examined among 1,177 patients with bipolar I disorder or bipolar II disorder, including 458 individuals treated with lithium carbonate or citrate, who were participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) cohort. SNPs showing the greatest evidence of association in Cox regression models were then examined for association with positive lithium response among 359 bipolar I or II disorderpatients treated with lithium carbonate or citrate in a second cohort from the University College London. RESULTS: The strongest association in the STEP-BD cohort (minimum p=5.5 x 10(-7)) was identified for a region on chromosome 10p15 (rs10795189). Of the regions showing suggestive evidence (p<5 x 10(-4)) of association with lithium response, five were further associated with positive lithium response in the University College London cohort, including SNPs in a region on chromosome 4q32 spanning a gene coding for the glutamate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) receptor GRIA2. CONCLUSIONS: Multiple novel loci merit further examination for association with lithium response in bipolar disorderpatients, including one region that spans the GRIA2 gene, for which expression has been shown to be regulated by lithium treatment.
Authors: Lewis L Judd; Hagop S Akiskal; Pamela J Schettler; William Coryell; Jean Endicott; Jack D Maser; David A Solomon; Andrew C Leon; Martin B Keller Journal: Arch Gen Psychiatry Date: 2003-03
Authors: Lewis L Judd; Hagop S Akiskal; Pamela J Schettler; Jean Endicott; Jack Maser; David A Solomon; Andrew C Leon; John A Rice; Martin B Keller Journal: Arch Gen Psychiatry Date: 2002-06
Authors: Gary S Sachs; Michael E Thase; Michael W Otto; Mark Bauer; David Miklowitz; Stephen R Wisniewski; Philip Lavori; Barry Lebowitz; Mathew Rudorfer; Ellen Frank; Andrew A Nierenberg; Maurizio Fava; Charles Bowden; Terence Ketter; Lauren Marangell; Joseph Calabrese; David Kupfer; Jerrold F Rosenbaum Journal: Biol Psychiatry Date: 2003-06-01 Impact factor: 13.382
Authors: Mauricio Tohen; Carlos A Zarate; John Hennen; Hari-Mandir Kaur Khalsa; Stephen M Strakowski; Priscilla Gebre-Medhin; Paola Salvatore; Ross J Baldessarini Journal: Am J Psychiatry Date: 2003-12 Impact factor: 18.112
Authors: Thomas G Schulze; Martin Alda; Mazda Adli; Nirmala Akula; Raffaella Ardau; Elise T Bui; Caterina Chillotti; Sven Cichon; Piotr Czerski; Maria Del Zompo; Sevilla D Detera-Wadleigh; Paul Grof; Oliver Gruber; Ryota Hashimoto; Joanna Hauser; Rebecca Hoban; Nakao Iwata; Layla Kassem; Tadafumi Kato; Sarah Kittel-Schneider; Sebastian Kliwicki; John R Kelsoe; Ichiro Kusumi; Gonzalo Laje; Susan G Leckband; Mirko Manchia; Glenda Macqueen; Takuya Masui; Norio Ozaki; Roy H Perlis; Andrea Pfennig; Paola Piccardi; Sara Richardson; Guy Rouleau; Andreas Reif; Janusz K Rybakowski; Johanna Sasse; Johannes Schumacher; Giovanni Severino; Jordan W Smoller; Alessio Squassina; Gustavo Turecki; L Trevor Young; Takeo Yoshikawa; Michael Bauer; Francis J McMahon Journal: Neuropsychobiology Date: 2010-05-08 Impact factor: 2.328