Counteracting Risperidone-Induced Hyperprolactinemia in Youths

描述(申请人提供)：各种精神疾病与低骨密度(BMD)有关，一些精神药物，如利培酮，可能会导致高催乳素血症(HiPRL)，从而加剧这种风险。由于成年早期达到的骨量决定了一个人未来低骨密度及其后遗症的风险，NIH确定，迫切需要采取干预措施来识别高危患者并优化峰值骨密度。这是最重要的，因为抗精神病药物的治疗通常持续数年，使HiPRL更有可能阻碍BMD。这项有指导的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所需的专业知识。职业发展部分与钙和维生素D补充剂的试验相结合，以优化利培酮引起的HiPRL儿童的骨密度。它还旨在确定可能与这一不良事件的病理生理学有关的基因变体。虽然精神疾病患者由于精神病理学、治疗和不良的生活习惯而增加了低骨密度的风险，但精神病学的研究尚未使用目前可用的新的敏感方法。在这个培训和研究的翻译计划中，候选人将结合和扩展他的共同发起人和顾问的知识，以开发在精神病理学中评估骨密度、预防性干预的有效性以及可能夸大HiPRL易感性的基因变异方面的专业知识。候选人的长期职业目标包括识别与儿童精神药物有关的潜在和临床重大不良事件，并开发预防性干预措施。识别与这些不良事件相关的遗传预测因素将使设计的干预措施更有选择性地成为目标。这项工作的总体目标是提高这些有效药物的安全性。这项拟议的工作将在爱荷华大学进行，这是一所主要的学术机构，对理解荷尔蒙介导的低骨密度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.