title: Variants of the serotonin transporter gene, selective serotonin reuptake inhibitors, and bone mineral density in risperidone-treated boys: a reanalysis of data from a cross-sectional study with emphasis on pharmacogenetics.
abstract: OBJECTIVE
  Selective serotonin reuptake inhibitors (SSRIs) may reduce bone mineral density (BMD). Here, we investigate whether variants of the serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene moderate this association in boys.
  
  
  METHODS
  Between November 2005 and August 2009, medically healthy boys, aged 7 to 17 years, were enrolled in a cross-sectional study exploring the effect of risperidone-induced hyperprolactinemia on BMD. Volumetric BMD of the ultradistal radius was measured using peripheral quantitative computed tomography, and areal BMD of the lumbar spine was estimated using dual energy x-ray absorptiometry. Multiple linear regression analysis tested whether the 5-HTTLPR genotypes interacted with SSRI treatment status to affect BMD, adjusting for relevant confounders. Participant enrollment was conducted at the University of Iowa, Iowa City.
  
  
  RESULTS
  Of 108 boys (mean ± SD age = 11.7 ± 2.8 years), with DSM-IV clinical diagnoses based on chart review, 52% (n = 56) had been taking an SSRI for a median duration of 2.8 years. After adjusting for pubertal development, anthropometric measures, physical activity, calcium intake, and prolactin concentration, there was a significant 5-HTTLPR genotype × SSRI treatment interaction effect on total lumbar spine BMD z score (P < .05) in non-Hispanic whites. The interaction effect on BMD at the ultradistal radius failed to reach statistical significance. Among LS genotype carriers, those treated with SSRIs had lower lumbar BMD z score and trabecular BMD at the radius compared to those not treated (P < .02 and P < .008, respectively).
  
  
  CONCLUSIONS
  These findings add to the growing evidence implicating the serotonin system in bone metabolism. They suggest the potential use of 5-HTTLPR genotypes to guide the safer long-term prescribing of SSRIs in youths. However, prospective confirmation in a controlled matched population is warranted.
authors.affiliation: Department of Psychiatry, The University of Iowa Carver College of Medicine, Psychiatry Research, Iowa City, IA, USA. chadi-calarge@uiowa.edu
authors.forename: Chadi A
authors.initials: CA
authors.lastname: Calarge
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Ellingrod
authors.forename: Bridget
authors.initials: B
authors.lastname: Zimmerman
authors.forename: Michael M
authors.initials: MM
authors.lastname: Bliziotes
authors.forename: Janet A
authors.initials: JA
authors.lastname: Schlechte
mesh_terms: D000293:Adolescent; D000483:Alleles; D014150:Antipsychotic Agents / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D002648:Child; D003430:Cross-Sectional Studies; D014644:Genetic Variation / Q000187:drug effects / Q000502:physiology; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic / Q000187:drug effects; D018967:Risperidone / Q000627:therapeutic use*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human