Genetic variation in the serotonin transporter and HTR1B receptor predicts reduced bone formation during serotonin reuptake inhibitor treatment in older adults.
OBJECTIVE
Studies have reported an association between serotonin reuptake inhibitors (SRIs) and accelerated bone loss. Genetic variation in the serotonin system might modulate bone metabolism changes during SRI treatment. In a clinical trial we examined functional genetic polymorphisms of serotonin transporter and receptors involved in bone metabolism to determine whether they predict changes in bone metabolism during SRI treatment.


METHODS
In 69 adults (age ≥ 60) participating in a 12-week, open-label trial of the SRI venlafaxine for major depression, serum markers of bone formation (P1NP) and resorption (β-CTX) were assayed before and after treatment. Participants were genotyped for putative high- versus low-expressing polymorphisms in the serotonin transporter (5HTTLPR) and 1B receptor (HTR1B) genes.


RESULTS
Bone formation was significantly reduced with administration of venlafaxine in participants with the high-expressing 5HTTLPR genotype and those with the low-expressing HTR1B genotype. This primarily occurred in individuals with the combination of the high-expressing 5HTTLPR genotype and the low-expressing HTR1B genotype.


CONCLUSIONS
These preliminary findings indicate that genetic variation in the serotonin receptors predicts changes in bone metabolism during SRI use. If these results are replicated and clinically confirmed, we will have identified a genetic subgroup at high risk for deleterious bone outcomes with the use of SRIs.
Department of Psychiatry, Washington University School of Medicine , St. Louis, MO , USA.
Lauren D
LD
Garfield
Daniel J
DJ
Müller
James L
JL
Kennedy
Benoit H
BH
Mulsant
Charles F
CF
Reynolds
Steven L
SL
Teitelbaum
Roberto
R
Civitelli
David
D
Dixon
Alexandre A
AA
Todorov
Eric J
EJ
Lenze
D000368:Aged; D001862:Bone Resorption / Q000097:blood / Q000235:genetics; D003511:Cyclohexanols / Q000008:administration & dosage / Q000009:adverse effects*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000069470:Venlafaxine Hydrochloride
D003511:Cyclohexanols; D044302:Receptor, Serotonin, 5-HT1B; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; C470302:HTR1B protein, human
aged; biological markers; bone diseases; pharmacogenetics; serotonin