title: Pharmacogenomics of antidepressant induced mania: a review and meta-analysis of the serotonin transporter gene (5HTTLPR) association.
abstract: BACKGROUND
  Antidepressants can trigger a rapid mood switch from depression to mania. Identifying genetic risk factors associated with antidepressant induced mania (AIM) may enable individualized treatment strategies for bipolar depression. This review and meta-analysis evaluates the evidence for association between the serotonin transporter gene promoter polymorphism (5HTTLPR) and AIM.
  
  
  METHODS
  Medline up to November 2009 was searched for key words bipolar, antidepressant, serotonin transporter, SLC6A4, switch, and mania.
  
  
  RESULTS
  Five studies have evaluated the SLC6A4 promoter polymorphism and AIM in adults (total N=340 AIM+ cases, N=543 AIM- controls). Although a random effects meta-analysis showed weak evidence of association of the S allele with AIM+ status, a test of heterogeneity indicated significant differences in estimated genetic effects between studies. A similar weak association was observed in a meta-analysis based on a subset of three studies that excluded patients on mood stabilizers; however the result was again not statistically significant.
  
  
  CONCLUSIONS
  Few pharmacogenomic studies of antidepressant treatment of bipolar disorder have been published. The completed studies were underpowered and often lacked important phenotypic information regarding potential confounders such as concurrent use of mood stabilizers or rapid cycling.
  
  
  CONCLUSIONS
  There is insufficient published data to confirm an association between 5HTTLPR and antidepressant induced mania. Pharmacogenomic studies of antidepressant induced mania have high potential clinical impact provided future studies are of adequate sample size and include rigorously assessed patient characteristics (e.g. ancestry, rapid cycling, concurrent mood stabilization, and length of antidepressant exposure).
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States. Electronic address: biernacka.joanna@mayo.edu.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Biernacka
authors.affiliation: Lindner Center of HOPE, Mason, OH, United States; University of Cincinnati College of Medicine, Cincinnati, OH, United States; The Bipolar Collaborative Network, Bethesda, MD, United States.
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN, United States.
authors.forename: Scott
authors.initials: S
authors.lastname: Crow
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Alexis
authors.initials: A
authors.lastname: Sharp
authors.affiliation: Department of Psychiatry, Austin Medical Center, Mayo Health System, Austin, MN, United States.
authors.forename: Joachim
authors.initials: J
authors.lastname: Benitez
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Marin
authors.initials: M
authors.lastname: Veldic
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Simon
authors.initials: S
authors.lastname: Kung
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.affiliation: The Bipolar Collaborative Network, Bethesda, MD, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Post
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States.
authors.forename: David
authors.initials: D
authors.lastname: Mrazek
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States; The Bipolar Collaborative Network, Bethesda, MD, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics*; D003863:Depression / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins