Counteracting Risperidone-Induced Hyperprolactinemia in Youths

描述（由申请人提供）：各种精神疾病与低骨矿物质密度（BMD）相关，一些精神药物（如利培酮）可通过引起高泌乳素血症（HiPRL）加剧这种风险。由于成年早期获得的骨量决定了一个人未来低BMD及其后遗症的风险，因此非常需要通过NIH确定的干预措施来识别风险患者并优化峰值BMD。这是最重要的，因为抗精神病药物治疗往往持续多年，使其更有可能是高泌乳素会阻碍骨密度。这种指导以患者为导向的研究职业发展奖（K23）应用程序将允许候选人在评估抗精神病药物引起的激素和代谢异常以及药物遗传学方面发展独特和必要的专业知识。职业发展部分与钙和维生素D补充试验相结合，以优化利培酮诱导的HiPRL儿童的BMD。它还旨在识别可能与该不良事件的病理生理学相关的基因变体。尽管由于精神病理学、治疗和不良的生活习惯，精神疾病患者出现低骨密度的风险增加，但精神病学研究尚未使用目前可用的新型敏感方法。在这个培训和研究的转化计划中，候选人将联合收割机和扩展他的共同赞助商和顾问的知识，以发展在精神病理学中BMD评估的专业知识，预防性干预的有效性，以及可能夸大对HiPRL的脆弱性的遗传变异。候选人的长期职业目标包括识别与儿童精神药物相关的潜在和临床显著不良事件，并制定预防干预措施。识别与这些不良事件相关的遗传预测因子将允许更有选择性地针对所设计的干预措施。这项工作的总体目标是提高这些有效药物的安全性。拟议的工作将在爱荷华州大学进行，该大学是一个首屈一指的学术机构，对理解骨介导的低BMD和精神药物基因组学有重大贡献。

DESCRIPTION (provided by applicant): 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.