Various psychiatric disorders are associated with low bone mineral density'(BMD) and some psychotropics, such as risperidone, can exacerbate this risk by causing hyperprolactinemia (HiPRL). Since bone mass achieved by early adulthood determines one's future risk for low BMD and its sequelae, interventions to identify at-risk patients and optimize peak BMD are greatly needed, as determined by the NIH. This is most significant since antipsychotic treatment often extends over years, making it more likely that HiPRL would hinder BMD. This Mentored Patient-Oriented Research Career Development Award (K23) application will allow the candidate to develop unique and needed expertise in the assessment antipsychotic-induced hormonal and metabolic abnormalities and in pharmacogenetics. The career development component is integrated with a trial of calcium and vitamin D supplementation to optimize BMD in children with risperidone-induced HiPRL. It also aims to identify variants of genes potentially linked to the pathophysiology of this adverse event. Although patients with mental illness are at increased risk for low BMD due to psychopathology, its treatment, and poor lifestyle habits, studies in psychiatry have not used the novel sensitive methods currently available. In this translational program of training and research, the candidate will combine and extend the knowledge of his cosponsors and consultants to develop expertise in the assessment of BMD in psychopathology, the efficacy of a preventative intervention, and genetic variants that could exaggerate the vulnerability to HiPRL. The long-term career goals of the candidate include identifying insidious and clinically significant adverse events associated with psychotropics in children and developing preventative interventions. The identification of genetic predictors associated with these adverse events will allow targeting the designed interventions more selectively. The overall aim of this work would be to improve the safety of these effective medications. The proposed work will be conducted at the University of Iowa, a premiere academic institution with major contributions to the understanding of hormonally-mediated low BMD and psychopharmacogenomics.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Interventions Committee for Disorders Involving Children and Their Families (ITVC)
Program Officer
Grabb, Margaret C
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University of Iowa
Schools of Medicine
Iowa City
United States
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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
Calarge, Chadi A; Ivins, Stephanie D; Motyl, Katherine J et al. (2013) Possible mechanisms for the skeletal effects of antipsychotics in children and adolescents. Ther Adv Psychopharmacol 3:278-93
Safer, Daniel J; Calarge, Chadi A; Safer, Alan M (2013) Prolactin serum concentrations during aripiprazole treatment in youth. J Child Adolesc Psychopharmacol 23:282-9
Calarge, Chadi Albert; Ziegler, Ekhard E (2013) Iron deficiency in pediatric patients in long-term risperidone treatment. J Child Adolesc Psychopharmacol 23:101-9
Turner, Catharyn A; Xie, Diqiong; Zimmerman, Bridget M et al. (2012) Iron status in toddlerhood predicts sensitivity to psychostimulants in children. J Atten Disord 16:295-303
Calarge, Chadi Albert; Miller, Del D (2011) Predictors of risperidone and 9-hydroxyrisperidone serum concentration in children and adolescents. J Child Adolesc Psychopharmacol 21:163-9
Calarge, Chadi A; Ellingrod, Vicki L; Zimmerman, Bridget et al. (2011) Variants of the serotonin transporter gene, selective serotonin reuptake inhibitors, and bone mineral density in risperidone-treated boys: a reanalysis of data from a cross-sectional study with emphasis on pharmacogenetics. J Clin Psychiatry 72:1685-90