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

描述（由申请人提供）：在精神分裂症综合征中识别单独的疾病“亚型”或“中间表型”将有助于未来对病因的研究，识别突出基因和生物标记，并使更有效的预防和干预成为可能。一种有希望的精神分裂症“亚型”，即“缺陷综合征”（DS），其特征是持续和原发性阴性症状。缺陷综合征与一般阴性症状的不同之处在于它强调原发性阴性症状、对预后的预测能力和特定的危险因素。虽然大量文献支持“缺陷”与“非缺陷”综合征精神分裂症的区分，但证据中存在一个重要的空白，本提案试图解决这一问题。研究方法上的担忧和地理上的限制使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)跨文化概括性。特别是，迄今为止没有研究有效地排除急性精神病和长期药物治疗在评估缺陷综合征的影响。本提案旨在通过对非西方国家（中国）一项具有里程碑意义的精神病学研究中获得的唯一具有代表性的非急性、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的二次数据分析来解决这一差距。利用这个以人群为基础的慢性、未经治疗的精神病患者样本——这些患者的疾病未经治疗的平均时间为10.5年，因此可能具有明显的临床特征，如更大的症状学——为缺陷综合征的结构有效性提供了一个非凡的测试。我们建议利用从中国4个省份（1.13亿成年人的抽样框架）分层随机样本中获得的389名诊断为精神障碍的患者的代表性样本。与之前的研究相比，该样本具有独特的优势：1)大样本（n=389）；2)具有代表性的、基于人群的抽样，通过临床医生管理的访谈获得数据；3)大量“未经治疗/最少治疗”的患者（n= 208），从而提供了一个独特的机会，可以在中国非急性、代表性的“未经治疗和最少治疗组”中全面测试“缺陷综合征”亚型的有效性。我们首先试图在样本中一组“大量接受药物治疗”的精神病患者（即有1次精神病住院治疗）中确认缺陷综合征的结构，然后在一组独特的“未经治疗或最低限度治疗”的精神病患者中评估缺陷综合征的结构有效性。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效度，以确定该亚型是否与西方样本中已建立的关键人口统计学和临床变量具有相同的相关性模式。在所有分析中，我们都控制了疾病对发育的影响。在中国治疗组中确认亏缺证的构效度将为检验Aim #2建立一个基线条件。2)在“未治疗或最低限度治疗”精神病患者组中识别DS病例并评估缺陷综合征的构念效度，以确定该亚型与中国“治疗”组在关键人口学和临床变量上的相关性模式是否相同。3)在全样本（n= 389）中探索两个治疗组和关键构念效变量之间的关系是否在各组之间存在差异。为了模拟“缺陷综合征分类”X“治疗组状态”的统计相互作用，我们将检验用于证明有缺陷综合征和非有缺陷综合征之间结构效度的变量分布是否因治疗组而异。这将是第一个利用未经治疗的、非急性的、基于人群的精神分裂症患者样本来建立缺陷综合征结构效度的研究，从而控制急性精神病、药物使用暴露、并在具有代表性的非西方样本中验证缺陷综合征。这项研究有望为精神分裂症中缺陷综合征作为一种独特的疾病“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。这个R03（小额拨款）将是哥伦比亚大学全球精神健康项目的几个提案中的第一个，该项目将启动一个新的和富有成效的研究项目，研究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方面。

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.