Examining the Deficit Syndrome Subtype in an Untreated and Treated Non-Acute, Rep

检查未经治疗和治疗的非急性、代表的缺陷综合症亚型

• 批准号: 8178762
• 负责人: LAWRENCE H YANG
• 金额: $ 8万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-05 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8178762
• 关键词: Accounting; Acute; Address; Adult; Age of Onset; Applications Grants; Biological; Biological Markers; Biological Markers; China; Chronic; Classification; Clinical; Data; Data Analyses; Development; Diagnosis; Etiology; Event; Exposure to; Future; Genes; Grant; Hospitalization; Intervention Studies; Interview; Knowledge; Literature; Mental Health; Mental disorders; Outcome; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Physiology; Preventive Intervention; Province; Proxy; Psychotic Disorders; Records; Research; Research Personnel; Risk Factors; Sampling; Schizophrenia; Signs and Symptoms; Societies; Statistical Models; Symptoms; Syndrome; Testing; Time; Validation; Work; base; deficit syndrome; disability; disorder subtype; epidemiology study; genetic linkage; novel; population based; programs; research study; social; treatment response

DESCRIPTION (provided by applicant): The identification of separate disease 'subtypes' or 'intermediate phenotypes' within the syndrome of schizophrenia would facilitate future research on etiology, identification of salient genes and biological markers, and enable more effective prevention and intervention. One promising schizophrenia 'subtype', the 'deficit syndrome' (DS), is characterized by persistent and primary negative symptoms. The deficit syndrome differs from general negative symptoms in its emphasis on primary negative symptoms, predictive power for outcomes, and specific risk factors. While a substantial literature supports the differentiation of 'deficit' from 'non-deficit' syndrome schizophrenia, there is an important gap in the evidence, which this proposal seeks to address. Methodological concerns and geographic limitations of studies have not allowed researchers to fully answer three important questions concerning this subtype: 1) effects of acute psychosis; 2) potential effects of medication treatment; 3) cross-cultural generalizability. In particular, no studies to date have effectively ruled out both the effects of acute psychosis and prolonged medication treatment in the assessment of the deficit syndrome. This proposal seeks to address this gap via a secondary data analysis of the sole existing representative, non-acute, population-based, sample of 'untreated or minimally-treated' schizophrenia patients obtained from a landmark psychiatric epidemiology study in a non-Western context (China). Utilizing this population-based sample of chronic, untreated psychotic illness--who have had untreated illness for an average of 10.5 years and are thus likely to have distinct clinical features such as greater symptomatology--offers an extraordinary test for construct validity of the deficit syndrome. We propose to utilize a representative sample of 389 patients diagnosed with psychotic disorders obtained from a stratified random sample of 4 provinces in China (a sampling frame of 113 million adults). This sample offers unique advantages over prior studies in its: 1) large size (n=389); 2) representative, population-based sampling with data obtained via a clinician-administered interview; and 3) large numbers of 'untreated/minimally-treated' patients (n= 208), thus affording a unique opportunity to comprehensively test the validity of the 'deficit syndrome' subtype within a non-acute, representatively-sampled 'untreated and minimally-treated group' in China. We first seek to confirm the deficit syndrome construct in a group of psychotic patients 'substantially exposed to medication treatment' in this sample (i.e., havinge1 psychiatric hospitalizations), then to assess the construct validity of deficit syndrome within a unique 'untreated or minimally treated' group of psychotic patients. Our specific aims are: 1) To identify cases of deficit syndrome and assess construct validity of deficit syndrome among 'treated' patients with psychotic disorders in China to determine whether this subtype demonstrates the same pattern of correlations to key demographic and clinical variables already established in Western samples. We control for developmental effects of illness in all analyses. Confirming the construct validity of deficit syndrome among the treated group in China will establish a baseline condition to test Aim #2. 2) To identify cases of DS and assess construct validity of deficit syndrome among the 'untreated or minimally treated' psychotic patient group to determine whether this subtype shows the same pattern of correlations to key demographic and clinical variables as the 'treated' group in China. 3) To explore among the full sample (n= 389) whether the relationship between the two treatment groups and key construct validation variables differ in magnitude by group. To model statistical interaction of 'deficit syndrome categorization' X 'treatment group status', we will examine whether the distribution of our variables used to demonstrate construct validity between DS and non-DS varies by treatment groups This will be the first study to utilize an untreated, non-acute, population-based sample of schizophrenia patients to establish construct validity for deficit syndrome, thereby controlling for acute psychosis, exposure to medication use, and validating deficit syndrome in a representative, non-Western based sample. This study has promise to provide evidence for deficit syndrome as a distinct disease 'subtype' within schizophrenia, thus contributing to future etiological, genetic linkage, and intervention studies in schizophrenia. This R03 (small grant) will be the first of several proposals from the Global Mental Health Program at Columbia that will initiate a novel and productive program of research examining subtypes and course determinants of untreated schizophrenia in non-Western societies to examine schizophrenia's cross-cultural aspects. PUBLIC HEALTH RELEVANCE: Schizophrenia is the 9th leading cause of disability worldwide. Although schizophrenia is conceptualized as a single diagnosis, it is likely that the schizophrenia syndrome includes separate 'subtypes', each with distinct causes and physiology. This proposal seeks to advance our knowledge concerning a separate disease 'subtype' of schizophrenia-that of Deficit Syndrome, which is characterized by persistent and primary negative symptoms-by examining it for the first time in an 'untreated/minimally treated', non-acute group to facilitate future research on causes, identification of salient genes and biological markers, and enable more effective prevention and intervention of this chronic mental illness. This proposal will also work in conjunction with the Global Mental Health Program at Columbia to initiate a novel and productive program of research studying subtypes and course features of untreated schizophrenia to examine schizophrenia's cross-cultural aspects.

描述（由申请人提供）：精神分裂症综合征中单独疾病“亚型”或“中间表型”的鉴定将有助于未来的病因学研究、显着基因和生物标志物的鉴定，并实现更有效的预防和干预。一种有前景的精神分裂症“亚型”，即“缺陷综合征”（DS），其特征是持续的、原发性阴性症状。缺陷综合征与一般阴性症状的不同之处在于它强调主要阴性症状、结果的预测能力和特定的危险因素。虽然大量文献支持区分“缺陷”与“非缺陷”综合征精神分裂症，但证据方面存在重要差距，而本提案试图解决这一问题。研究的方法学问题和地理限制使得研究人员无法完全回答有关该亚型的三个重要问题：1）急性精神病的影响； 2）药物治疗的潜在影响； 3）跨文化的普遍性。特别是，迄今为止还没有研究有效排除急性精神病和长期药物治疗对缺陷综合征评估的影响。该提案旨在通过对从非西方背景下的一项具有里程碑意义的精神病学流行病学研究中获得的唯一现有代表性、非急性、基于人群的“未经治疗或最低限度治疗”精神分裂症患者样本进行二次数据分析来解决这一差距（中国）。利用这一基于人群的慢性、未经治疗的精神病样本（这些人平均患有未经治疗的疾病长达 10.5 年，因此可能具有明显的临床特征，例如更严重的症状），为缺陷的构建有效性提供了非凡的测试综合症。我们建议使用从中国 4 个省份的分层随机样本（1.13 亿成年人的抽样框架）中获得的 389 名被诊断患有精神障碍的患者作为代表性样本。该样本与之前的研究相比具有独特的优势：1）样本量大（n=389）； 2) 具有代表性的、基于人群的抽样，其数据是通过临床医生进行的访谈获得的； 3）大量“未经治疗/最低限度治疗”的患者（n = 208），从而提供了一个独特的机会，可以在非急性、代表性采样的“未经治疗和最低限度治疗”中全面测试“缺陷综合征”亚型的有效性中国的“治疗组”。我们首先试图在该样本中“大量接受药物治疗”的一组精神病患者（即，曾接受过精神病住院治疗）中确认缺陷综合征的构建，然后评估在独特的“未经治疗或最低限度治疗”的情况下缺陷综合征的构建有效性。 ' 一群精神病患者。我们的具体目标是： 1) 在中国“接受治疗”的精神障碍患者中识别缺陷综合征病例并评估缺陷综合征的结构有效性，以确定该亚型是否表现出与已在中国建立的关键人口和临床变量相同的相关模式。西方样品。我们在所有分析中控制疾病对发育的影响。确认中国治疗组中缺陷综合征的结构有效性将为测试目标 2 建立基线条件。 2) 识别 DS 病例并评估“未治疗或最低限度治疗”精神病患者组中缺陷综合征的构建有效性，以确定该亚型是否与中国“治疗”组表现出与关键人口和临床变量相同的相关模式。 3) 在完整样本 (n= 389) 中探索两个治疗组和关键构建验证变量之间的关系是否因组而异。为了模拟“缺陷综合征分类”X“治疗组状态”的统计交互作用，我们将检查用于证明 DS 和非 DS 之间的构建有效性的变量分布是否因治疗组而异。这将是第一项利用未经治疗的、非急性的、基于人群的精神分裂症患者样本，以建立缺陷综合征的结构有效性，从而控制急性精神病、药物使用暴露，并在代表性的、非西方样本中验证缺陷综合征。这项研究有望为缺陷综合征作为精神分裂症中一种独特的疾病“亚型”提供证据，从而有助于未来精神分裂症的病因学、遗传联系和干预研究。该 R03（小额赠款）将是哥伦比亚全球心理健康计划的多项提案中的第一个，该计划将启动一项新颖且富有成效的研究计划，检查非西方社会中未经治疗的精神分裂症的亚型和病程决定因素，以研究精神分裂症的跨文化影响。方面。 公共卫生相关性：精神分裂症是全球第九大导致残疾的原因。尽管精神分裂症被概念化为单一诊断，但精神分裂症综合征很可能包括单独的“亚型”，每种亚型都有不同的病因和生理学。该提案旨在增进我们对精神分裂症的一种单独疾病“亚型”的认识，即缺乏综合症，其特点是持续的、原发性阴性症状，通过首次在“未经治疗/最低限度治疗”、非-急性组，以促进未来对病因的研究，识别显着基因和生物标记，并能够更有效地预防和干预这种慢性精神疾病。该提案还将与哥伦比亚大学全球心理健康项目合作，启动一项新颖且富有成效的研究计划，研究未经治疗的精神分裂症的亚型和病程特征，以研究精神分裂症的跨文化方面。