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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH085005-04
Application #
8230650
Study Section
Interventions Committee for Disorders Involving Children and Their Families (ITVC)
Program Officer
Grabb, Margaret C
Project Start
2009-03-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
4
Fiscal Year
2012
Total Cost
$173,264
Indirect Cost
$12,834
Name
University of Iowa
Department
Psychiatry
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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Calarge, Chadi A; Schlechte, Janet A; Burns, Trudy L et al. (2015) The effect of psychostimulants on skeletal health in boys co-treated with risperidone. J Pediatr 166:1449-54.e1
Calarge, Chadi A; Burns, Trudy L; Schlechte, Janet A et al. (2015) Longitudinal examination of the skeletal effects of selective serotonin reuptake inhibitors and risperidone in boys. J Clin Psychiatry 76:607-13
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Bahr, S M; Tyler, B C; Wooldridge, N et al. (2015) Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children. Transl Psychiatry 5:e652
Calarge, Chadi A; Ziegler, Ekhard E; Del Castillo, Nicole et al. (2015) Iron homeostasis during risperidone treatment in children and adolescents. J Clin Psychiatry 76:1500-5
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
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
Del Castillo, Nicole; Zimmerman M, Bridget; Tyler, Billie et al. (2013) 759C/T Variants of the Serotonin (5-HT2C) Receptor Gene and Weight Gain in Children and Adolescents in Long-Term Risperidone Treatment. Clin Pharmacol Biopharm 2:110
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

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