Do Serotonin Reuptake Inhibitors (SSRIs) Affect Bone Mass in Adolescents
Condition: The Skeletal Effects of SSRIs
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients within one month of initiating treatment with SSRIs will be recruited, regardless
        of the indication for SSRIs.

        Unmedicated controls will be also recruited.
      
Biospecimen description: 
      serum plasma DNA whole blood Stools Urine Paxgene
    
Keywords: SSRI; serotonin transporter; DXA; pQCT; bone mass; adolescents