Chronic Atypical Neuroleptic Treatment

描述(申请人提供)：非典型的抗精神病药物，如利培酮和奎硫平，经常用于患有严重精神疾病的儿童和青少年。这些药物对正常生长和发育的影响目前尚不清楚。该项目将用利培酮、奎硫平或安慰剂治疗48只13-24个月大的正常发育的年轻辫尾猴(猕猴)，并将研究四个月的服药后时期。一岁的猴子在身体成熟、运动技能、生理和在物种寿命中达到的比例上与4岁的儿童发育相似。12名男性将接受为期4个月的低剂量利培酮或奎硫平治疗，然后每组8名男性将切换为高剂量治疗4个月。24名男性将被分配到安慰剂治疗中。在药物或安慰剂治疗之前、期间和之后，动物将接受以下方面的测试：(1)社会、情绪、探索性、学习和记忆、运动技能和感知行为；(2)健康、躯体生长、骨骼矿化、免疫系统状态和激素功能的身体评估。研究设计将允许组内和个体内的比较，以检查药物组的差异以及药物引起的个体增长率的变化。由于辫子猴表现出与人类相似的心理和躯体发育，该项目将确定人类儿童的发育方面可能受到这些药物慢性治疗的影响。

DESCRIPTION (provided by applicant): Atypical neuroleptics such as risperidone and quetiapine are being used frequently in children and adolescents with severe psychopathology. The effects of these agents on normal growth and development are currently unknown. This project will treat 48 normally developing young pigtail monkeys (Macaca nemestrina) with risperidone, quetiapine, or placebo from 13-24 months of age, and will study a four-month post-drug period. Monkeys at one year of age are developmentally similar to children at 4 years of age in physical maturation, motor skills, physiology, and proportion reached in the species lifespan. Twelve males will receive a low dose of risperidone or quetiapine for 4 months, and then 8 in each drug group will be switched to a high dose for 4 months. Twenty-four males will be assigned to the placebo condition. Animals will be tested before, during, and after drug or placebo treatment for (1) social, emotional, exploratory, learning and memory, motor skill, and perceptual behavior; and (2) physical assessments of health, somatic growth, bone mineralization, immune system status, and hormonal function. The study design will permit both between-group and within-individual comparisons to examine drug group differences as well as alterations in individual growth rates caused by the drugs. Since pigtail monkeys demonstrate psychological and somatic development comparable to humans, this project will identify aspects of development in human children that are likely to be affected by chronic treatment with these agents.