title: Bone growth in juvenile rhesus monkeys is influenced by 5HTTLPR polymorphisms and interactions between 5HTTLPR polymorphisms and fluoxetine.
abstract: Male rhesus monkeys received a therapeutic oral dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine daily from 1 to 3 years of age. Puberty is typically initiated between 2 and 3 years of age in male rhesus and reproductive maturity is reached at 4 years. The study group was genotyped for polymorphisms in the monoamine oxidase A (MAOA) and serotonin transporter (SERT) genes that affect serotonin neurotransmission. Growth was assessed with morphometrics at 4 month intervals and radiographs of long bones were taken at 12 month intervals to evaluate skeletal growth and maturation. No effects of fluoxetine, or MAOA or SERT genotype were found for growth during the first year of the study. Linear growth began to slow during the second year of the study and serotonin reuptake transporter (SERT) long polymorphic region (5HTTLPR) polymorphism effects with drug interactions emerged. Monkeys with two SERT 5HTTLPR L alleles (LL, putative greater transcription) had 25-39% less long bone growth, depending on the bone, than monkeys with one S and one L allele (SL). More advanced skeletal maturity was also seen in the LL group, suggesting earlier onset of puberty. An interaction between 5HTTLPR polymorphisms and fluoxetine was identified for femur and tibia growth; the 5HTTLPR effect was seen in controls (40% less growth for LL) but not in the fluoxetine treated group (10% less growth for LL). A role for serotonin in peripubertal skeletal growth and maturation has not previously been investigated but may be relevant to treatment of children with SSRIs.
authors.affiliation: Department of Environmental Toxicology, University of California, Davis, Davis, CA 95616, USA. Electronic address: msgolub@ucdavis.edu.
authors.forename: Mari S
authors.initials: MS
authors.lastname: Golub
authors.affiliation: California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Bulleri
authors.affiliation: California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Casey E
authors.initials: CE
authors.lastname: Hogrefe
authors.affiliation: Division of Morphological Sciences and Biostatistics, Boonshoft School of Medicine, Wright State University, Dayton, OH 45434, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sherwood
mesh_terms: D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D005473:Fluoxetine / Q000009:adverse effects*; D005838:Genotype; D008253:Macaca mulatta; D008297:Male; D020641:Polymorphism, Single Nucleotide; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*
chemical_list: D005473:Fluoxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Femur; Fluoxetine; Height; Rhesus; Serotonin; Skeletal maturation