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 selective serotonin reuptake inhibitors (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. We, here, propose to recruit, in a 2-year prospective observational study, 15 to 20 year-old participants upon the initiation of SSRI treatment. During the period of the Award, bone mineral density of the lumbar spine and whole body will be measured using dual x-ray absorptiometry and of the radius using peripheral quantitative computerized tomography. 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 healthy controls, of comparable age and sex distribution, we 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. This is consistent with the mission of the National Institute of Mental Health.

Public Health Relevance

Building on findings from animal studies, pediatric clinical trials, epidemiologic research in adults, and on preliminary findings from our laboratory in children and adolescents, this project aims to investigate whether 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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Study Section
Interventions Committee for Disorders Involving Children and Their Families (ITVC)
Program Officer
Vitiello, Benedetto
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University of Iowa
Schools of Medicine
Iowa City
United States
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Gillentine, Madelyn A; Lozoya, Ricardo; Yin, Jiani et al. (2018) CHRNA7 copy number gains are enriched in adolescents with major depressive and anxiety disorders. J Affect Disord 239:247-252
Coryell, William H; Langbehn, Douglas R; Norris, Andrew W et al. (2017) Polyunsaturated fatty acid composition and childhood adversity: Independent correlates of depressive symptom persistence. Psychiatry Res 256:305-311
Dindo, Lilian N; Recober, Ana; Haddad, Rita et al. (2017) Comorbidity of Migraine, Major Depressive Disorder, and Generalized Anxiety Disorder in Adolescents and Young Adults. Int J Behav Med 24:528-534
Calarge, Chadi A; Mills, James A; Janz, Kathleen F et al. (2017) The Effect of Depression, Generalized Anxiety, and Selective Serotonin Reuptake Inhibitors on Change in Bone Metabolism in Adolescents and Emerging Adults. J Bone Miner Res 32:2367-2374
Calarge, Chadi A; Mills, James A; Janz, Kathleen F et al. (2017) Body Composition in Adolescents During Treatment With Selective Serotonin Reuptake Inhibitors. Pediatrics 140:
Deumic, Emira; Butcher, Brandon D; Clayton, Anita D et al. (2016) Sexual Functioning in Adolescents With Major Depressive Disorder. J Clin Psychiatry 77:957-62
Coryell, William; Yolken, Robert; Butcher, Brandon et al. (2016) Toxoplasmosis Titers and past Suicide Attempts Among Older Adolescents Initiating SSRI Treatment. Arch Suicide Res 20:605-13
Coryell, William H; Butcher, Brandon D; Burns, Trudy L et al. (2016) Fat distribution and major depressive disorder in late adolescence. J Clin Psychiatry 77:84-9
Saha, Punam K; Liu, Yinxiao; Chen, Cheng et al. (2015) Characterization of trabecular bone plate-rod microarchitecture using multirow detector CT and the tensor scale: Algorithms, validation, and applications to pilot human studies. Med Phys 42:5410-25
Calarge, Chadi A; Butcher, Brandon D; Burns, Trudy L et al. (2014) Major depressive disorder and bone mass in adolescents and young adults. J Bone Miner Res 29:2230-7

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