Genetics of Parkinsonism in a Special Population of Untreated Schizophrenia

未经治疗的精神分裂症特殊人群中帕金森症的遗传学

• 批准号: 8032861
• 负责人: GABRIEL Alejandro DE ERAUSQUIN
• 金额: $ 16.24万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8032861
• 关键词: Address; Adverse effects; Affect; Age; Aggressive behavior; Antipsychotic Agents; Argentina; Attention; Attitude to Health; Award; Blood; Blood specimen; Bradykinesia; Characteristics; Classification; Clinical; Cognitive; Cognitive deficits; Collection; Consent; Control Groups; DNA; Data; Databases; Deltastab; Dependence; Development; Diagnosis; Diagnostic; Diamond; Dimensions; Early Diagnosis; Early treatment; Enrollment; Epidemiology; Equipment and supply inventories; First Degree Relative; Funding; Future; General Population; Genes; Genetic; Genetic Variation; Genomics; Goals; Health; Health system; Heritability; High Prevalence; Image; Impairment; Individual; Institution; Interview; Language; Life; Link; Master' s Degree; Measures; Memory impairment; Mental Health; Mental disorders; Mentorship; Midbrain structure; Motor; Movement; Movement Disorders; Multivariate Analysis; Muscle Rigidity; Neurobiology; Neurocognitive; Neurologic; Neurologic Examination; Neurologist; Neurology; Newly Diagnosed; Nicotine; Nicotine Dependence; Noise; Outcome; Parkinson Disease; Parkinsonian Disorders; Participant; Pathway interactions; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Population; Population Control; Predisposition; Prevalence; Prevention; Principal Investigator; Province; Psychiatrist; Psychiatry; Psychotic Disorders; Quality of life; Quantitative Trait Loci; Recruitment Activity; Research; Research Personnel; Risk; Sampling; Scanning; Schedule; Schizophrenia; Severities; Sex Education; Short-Term Memory; Siblings; Signal Transduction; Single Nucleotide Polymorphism; Smoke; Smoker; Smoking; Substance Addiction; Substantia nigra structure; Surveys; Symptoms; Syndrome; Temperament; Testing; Training; Transportation; Tremor; Ultrasonography; Universities; Visuospatial; Washington; Work; base; career; case control; clinical Diagnosis; compliance behavior; deficit syndrome; design; endophenotype; executive function; field survey; genetic epidemiology; genome wide association study; improved; indexing; mRNA Expression; medical schools; meetings; motor impairment; named group; neurobiological mechanism; neuropsychiatry; neuropsychological; non-smoker; outreach; patient population; prevent; proband; professor; programs; protective effect; smoking prevalence; tool; trait

DESCRIPTION (provided by applicant): The candidate is a neurologist/psychiatrist with training in neurobiology, and an assistant professor of psychiatry and neurology at the Washington University School of Medicine (WUStL), a world leading institution in genetics and epidemiology of psychiatric disorders. The candidate's immediate goal is to complete a master's degree in epidemiology and genetics to maximize opportunities afforded by his currently funded research and under the mentorship of Dr. Cloninger and Dr. Goate. His long term goal is to concentrate his research career on the study of the genetic control of the relationship between parkinsonism and schizophrenia. Project. Parkinsonism is highly prevalent in newly diagnosed -untreated- patients with schizophrenia; its presence predicts greater susceptibility to neuroleptic-induced side effects, reduced treatment compliance and poorer outcome. Smoking has a negative association with parkinsonism, whereas hyperechogenicity of the substantia nigra, executive function and working memory deficits, and increased harm avoidance on the temperament and character inventory are all positively associated with motor impairment. These diverse phenotypic manifestations are related to a single neurobiological mechanism, namely decreased dopaminergic function. Studying untreated patients prevents the noise introduced into such phenotypic manifestations by the effects of antipsychotic drugs, and therefore will permit isolation of the genetic signal from environmental noise (represented by treatment). We identified a population with untreated schizophrenia, and collected a pilot sample to study the clinical, neuropsychological and neurological characteristics of patients, their first degree relatives, and culturally appropriate controls. We propose to expand the sample. With the funds of this award we will focus on the clinical characterization of the probands and their siblings as well as of controls and their siblings to investigate the heritability of a composite endophenotype including parkinsonism, smoking, cognitive deficit and hyperechogenicity of the substantia nigra. Towards the end of the award period we will work on an Roi application to study the relationship of the proposed phenotype to quantitative trait loci (QTL). The major relevance of the proposed research lies on the possibility of testing if a neurobiologically well defined set of individual characteristics is genetically determined. Because these deficits possibly predate the onset of psychosis, we believe our strategy might provide tools for early detection and early intervention, possibly leading to prevention of psychosis in subjects at-risk for schizophrenia. Lastly, we anticipate that our research strategy may indicate new ways to study and address the increased vulnerability of schizophrenic patients to nicotine dependence.

描述（由申请人提供）：候选人是一位接受过神经生物学培训的神经科医生/精神病学家，也是华盛顿大学医学院（WUStL）的精神病学和神经病学助理教授，华盛顿大学医学院是世界领先的精神疾病遗传学和流行病学机构。该候选人的近期目标是在 Cloninger 博士和 Goate 博士的指导下完成流行病学和遗传学硕士学位，以最大限度地利用他目前资助的研究提供的机会。他的长期目标是将他的研究生涯集中在帕金森症和精神分裂症之间关系的基因控制研究上。项目。帕金森症在新诊断且未经治疗的精神分裂症患者中非常普遍；它的存在预示着更容易受到抗精神病药物引起的副作用、治疗依从性降低和结果较差。吸烟与帕金森病呈负相关，而黑质的高回声、执行功能和工作记忆缺陷以及气质和性格清单上的伤害避免增加都与运动障碍呈正相关。这些不同的表型表现与单一的神经生物学机制有关，即多巴胺能功能下降。研究未经治疗的患者可以防止抗精神病药物的作用将噪音引入到此类表型表现中，因此可以将遗传信号与环境噪音（以治疗为代表）分开。我们确定了未经治疗的精神分裂症人群，并收集了试点样本来研究患者、其一级亲属以及文化上适当的对照的临床、神经心理学和神经学特征。我们建议扩大样本。利用该奖项的资金，我们将重点关注先证者及其兄弟姐妹以及对照及其兄弟姐妹的临床特征，以研究复合内表型的遗传力，包括帕金森病、吸烟、认知缺陷和黑质高回声。在奖励期结束时，我们将开展 Roi 应用程序，以研究拟议表型与数量性状基因座 (QTL) 的关系。拟议研究的主要相关性在于测试神经生物学上明确定义的一组个体特征是否是由基因决定的可能性。由于这些缺陷可能早于精神病发作，我们相信我们的策略可能为早期发现和早期干预提供工具，可能有助于预防有精神分裂症风险的受试者的精神病。最后，我们预计我们的研究策略可能会指明研究和解决精神分裂症患者对尼古丁依赖的脆弱性增加的新方法。