Association of the serotonin transporter-linked polymorphic region genotype with lower bone mineral density

M. I. Lapid, S. Kung, M. A. Frye, J. M. Biernacka, J. R. Geske, M. T. Drake, M. D. Jankowski, B. L. Clarke

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1 Scopus citations


The serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) S allele is linked to pathogenesis of depression and slower response to selective serotonin reuptake inhibitors (SSRIs); depression and SSRIs are independently associated with bone loss. We aimed to determine whether 5-HTTLPR was associated with bone loss. This crosssectional study included psychiatric patients with both 5-HTTLPR analysis and bone mineral density (BMD) assessment (hip and spine Z-scores if age o50 years and T-scores if ⩾ 50 years). BMD association with 5-HTTLPR was evaluated under models with additive allele effects and dominant S allele effects using linear regression models. Patients were stratified by age ( o50 and ⩾ 50 years) and sex. Of 3016 patients with 5-HTTLPR genotyping, 239 had BMD assessments. Among the younger patients, the S allele was associated with lower Z-scores at the hip (P = 0.002, dominant S allele effects; P = 0.004, additive allele effects) and spine (P = 0.0006, dominant S allele effects; P = 0.01, additive allele effects). In sex-stratified analyses, the association of the S allele with lower BMD in the younger patients was also significant in the subset of women (P ⩽ 0.003 for both hip and spine BMD under the additive allele effect model). In the small group of men younger than 50 years, the S allele was marginally associated with higher spine BMD (P = 0.05). BMD T-scores were not associated with 5-HTTLPR genotypes in patients 50 years or older. The 5-HTTLPR variants may modify serotonin effects on bone with sex-specific effects.

Original languageEnglish (US)
Article numbere1213
JournalTranslational psychiatry
Issue number8
StatePublished - 2017

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry


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