Building on findings from animal studies, pediatric clinical trials, epidemiologic research
in adults, and on preliminary findings from the investigators' laboratory in children and
adolescents, this project aims to investigate whether selective serotonin reuptake inhibitors
(SSRIs), a group of widely-used psychotropics, are associated with impaired bone
mineralization in youths. Establishing such an association is a first step in a process that
would eventually involve developing preventative interventions. Identifying genetic factors
that place certain youths at higher risks for this side effect would ultimately allow
clinicians to tailor treatment to the needs and vulnerabilities of each youth, moving the
field closer towards individualized medicine.
Bone mass achieved by early adulthood is a major determinant of lifetime risk for
osteoporosis. Therefore, optimizing peak bone mass is crucial to avoiding bone fracture with
its associated morbidity and mortality.
Emerging evidence suggests that serotonin plays a central role in bone metabolism. For
example, preclinical experiments have shown that bone cells express the serotonin transporter
and a variety of functional serotonin receptors whose activity modulates bone turnover.
Epidemiologic studies have linked SSRIs to reduced bone mineral density and increased
fracture risk in the elderly. SSRIs are widely used in youths to treat a number of
psychiatric disorders. However, while their short-term efficacy and safety have been
established, their long-term safety remains little investigated.
The investigators aim to recruit, in a 2-year prospective observational study, 15 to 20
year-old participants upon the initiation of SSRI treatment. During the study period, bone
mineral density of the lumbar spine and whole body will be measured using dual-energy x-ray
absorptiometry (DXA) and of the radius using peripheral quantitative computed tomography
(pQCT). A detailed psychiatric assessment will be conducted to control for psychopathology,
as a potential confounding factor affecting bone mineralization. Changes in psychiatric
treatment during the follow up period will also be documented and accounted for. By using a
group of controls, of comparable age and sex distribution, the investigators aim to evaluate
1) whether psychopathology, at baseline, is associated with low bone mass, 2) if treatment
with SSRIs suppresses bone mineralization, and 3) if the discontinuation of the SSRI is
followed by a restoration of bone mineral accrual. 4) Furthermore, genetic testing will
investigate whether variants of the serotonin system genes moderate the effect of SSRI
treatment on bone mineral density.
In sum, this work aims to improve the long-term safety of psychiatric treatments in order to
optimize functioning and the quality of life of those who suffer from psychiatric disorders.
1. Age 15 to 20 years old (inclusive).
2. Treatment with an SSRI, regardless of the indication, having been started within one
month. This criterion does not apply to controls. SSRIs include: fluoxetine,
citalopram, escitalopram, sertraline, paroxetine, and fluvoxamine.
3. Ability to provide consent.
1. Age- and sex-adjusted height Z-score < -2 or > 2.
2. Concomitant treatment with other antidepressants, psychostimulants, or mood
stabilizers and antipsychotics. Treatment with benzodiazepines, low dose trazodone,
alpha-2 agonists, and antihistaminergic agents will be allowed.
3. Presence of illicit drug and/or alcohol dependence.
5. Primary bone diseases (e.g., Paget's disease, osteogenesis imperfecta, rheumatoid
6. Potential secondary bone disease (e.g., due to chronic inflammatory diseases,
diabetes, hypo- or hyperparathyroidism, hyperthyroidism, growth hormone deficiency,
and other endocrine disturbances, history of childhood cancer, or prior
7. Chronic disorders involving a vital organ (heart, lung, liver, kidney, brain) and
8. Malnutrition conditions (e.g., chronic diarrhea, inflammatory bowel disease) or lead
9. Chronic use of drugs affecting bone metabolism (e.g., oral corticosteroids).
10. Inability to cooperate with the BMD measurements.
11. Eating disorders, due to their potential effect on BMD.
12. If a senior in high school, plan to join an out-of-state college.