This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.

Article

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

Chadi A. Calarge, MD; Vicki L. Ellingrod, PharmD; Bridget Zimmerman, PhD; Michael M. Bliziotes, MD; and Janet A. Schlechte, MD

Published: December 15, 2011

Article 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.

Method: 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.

J Clin Psychiatry 2011;72(12):1685-1690

Submitted: April 26, 2010; accepted December 22, 2010

(doi:10.4088/JCP.10m06198).

Corresponding author: Chadi A. Calarge, MD, Department of Psychiatry, The University of Iowa Carver College of Medicine, Psychiatry Research, 2-209 MEB, 500 Newton Rd, Iowa City, IA ([email protected]).

Volume: 72

Quick Links: Child and Adolescent , Populations

Continue Reading…

Subscribe to read the entire article

$40.00

Buy this Article as a PDF