Behavioral Studies of Carriers for Cholesterol Biosynthesis Disorders

胆固醇生物合成障碍携带者的行为研究

• 批准号: 8936527
• 负责人: CORNELIUS F BOERKOEL
• 金额: $ 18万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8936527
• 关键词: Area; Behavior; Behavior Therapy; Behavioral; Brain; British Columbia; Cessation of life; Cholesterol; Chondrodysplasia Punctata; Cohort Studies; Communities; Conduct Disorder; Data; Defect; Development; Disease; Exfoliative Dermatitis; Female; Functional Magnetic Resonance Imaging; General Population; Goals; Individual; Lead; Limb structure; Mental disorders; Metabolic Diseases; Metabolism; Mood Disorders; Mutation; Neurons; Oxidases; Pathology; Personality; Personality Assessment; Personality Disorders; Personality Traits; Phenotype; Play; Predisposition; Principal Investigator; Problem behavior; Questionnaires; Recruitment Activity; Role; Schedule; Short-Term Memory; Site; Smith-Lemli-Opitz Syndrome; Sorting - Cell Movement; Sterol Biosynthesis Pathway; Sterols; Suicide; Suicide attempt; Syndrome; Testing; Therapeutic Intervention; Universities; Violence; Work; anti social; base; cholesterol biosynthesis; hemodynamics; high risk; improved; insight; isoprenoid; mutation carrier; novel marker; prospective; response; tool; trait

Project 5 - Several studies have demonstrated an association between low cholesterol and both violent death (including suicide) and psychiatric disorders such as antisocial disorder, affective disorders, personality disorders and conduct disorder. Based on this observation, we hypothesized that carriers of mutations associated with cholesterol synthesis might also have a higher risk for behavioral problems. The aim of this study is to characterize the behavioral phenotype in carriers of disorders of sterol metabolism associated with low cholesterol, including Smith-Lemli Opitz syndrome, CK syndrome, SC4MOL deficiency, CHILD syndrome and chondrodysplasia punctata 2. A total of 144 individuals (75 subjects and 69 controls) will be recruited from the 5 sites (UBC, OHSU, UNMC, CCHMC, and UPMC) as part of the STAIR consortium. Our study will be done in 2 parts. Firstly, well validated personality disorder questionnaires (Dimensional Assessment of Personality Pathology-Basic Questionnaire [DAPP-BQ], the Schedule for Nonadaptive and Adaptive Personality-2 [SNAP-2]) will be administered to all subjects and 30 controls to identify aberrant behavioral traits. Secondly, to clarify the functional brain changes associated with these behaviors, the hemodynamic responses to working memory tasks will be examined using fMRI. Fifty one subjects (chosen randomly from the above stated 75 subjects) and 39 controls will undergo this part of the study. Behavioral and fMRI Data will be analyzed at UBC with the help of the the STAIR statistical core. Based on our preliminary data, we anticipate finding significant changes in behavior amonst carriers of sterol biosynthesis disorders compared to controls. In addition, we predict that the neuron activation seen in carriers of sterol metabolism disorders will be significantly lower then controls. The long term goal of this study is through the use of the proposed tools, find new markers that could potentially lead to improved behavioral therapies not only for disorders of cholesterol synthesis but also for individuals in the general population that suffer from similar behaviors.

项目5 -几项研究表明，低胆固醇与暴力死亡（包括自杀）和精神障碍（如反社会障碍、情感障碍、人格障碍和行为障碍）之间存在关联。基于这一观察，我们假设与胆固醇合成相关的突变携带者也可能有更高的行为问题风险。本研究的目的是描述与低胆固醇相关的固醇代谢疾病携带者的行为表型，包括Smith-Lemli Opitz综合征、CK综合征、SC 4 MOL缺乏症、CHILD综合征和点状软骨发育不良2。作为STAIR联合体的一部分，将从5个研究中心（UBC、OHSU、UNMC、CCHMC和UPMC）共招募144名个体（75名受试者和69名对照）。 我们的研究将分两部分进行。首先，将对所有受试者和30名对照者进行充分验证的人格障碍问卷调查（人格病理学维度评估-基本问卷[DAPP-BQ]，非适应性和适应性人格量表-2 [SNAP-2]），以识别异常行为特征。其次，为了阐明与这些行为相关的脑功能变化，将使用fMRI检查工作记忆任务的血流动力学反应。51例受试者（从上述75例受试者中随机选择）和39例对照受试者将接受本部分研究。行为和fMRI数据将在UBC的STAIR统计核心的帮助下进行分析。根据我们的初步数据，我们预期发现与对照组相比，固醇生物合成障碍的携带者的行为发生了显著变化。此外，我们预测，在固醇代谢紊乱的携带者中观察到的神经元活化将显著低于对照组。这项研究的长期目标是通过使用所提出的工具，找到新的标记物，这些标记物可能不仅会改善胆固醇合成障碍的行为疗法，而且还会改善普通人群中患有类似行为的个体的行为疗法。