Examining Deficit Syndrome in an Untreated, Representative SCZ Cohort in China

描述(申请人提供)：识别精神分裂症综合征中不同的疾病‘亚型’或‘中间表型’将有助于未来对病因学的研究，识别显著基因和生物标志物，并使更有效的预防和干预。精神分裂症的一个有希望的“亚型”--“缺陷综合征”(DS)，其特征是持续的和主要的阴性症状。缺陷综合征与一般阴性症状的不同之处在于，它强调主要的阴性症状，对结果的预测力，以及特定的危险因素。虽然有大量文献支持区分“缺陷”和“非缺陷”综合征精神分裂症，但在证据上存在一个重要的差距，这项建议试图解决这一问题。研究的方法论问题和地域限制使研究人员不能完全回答关于这一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)跨文化的概括性。特别是，到目前为止，还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方面的影响。这项建议试图通过对现有唯一具有代表性的非急性、基于人群的精神分裂症患者样本的二次数据分析来解决这一差距，这些样本是从一项里程碑式的非西方精神病学流行病学研究中获得的(中国)。利用这种以人群为基础的未经治疗的慢性精神病样本--他们平均有10.5年未经治疗的疾病，因此可能具有明显的临床特征，如更严重的症状--为缺陷综合征的结构效度提供了一个非凡的测试。我们建议使用一个具有代表性的样本，从中国4个省的分层随机抽样中获得389例精神障碍患者(抽样框架为1.13亿成年人)。与以前的研究相比，本样本在以下方面具有独特的优势：1)规模大(n=389)；2)具有代表性的以总体为基础的抽样，通过临床医生管理的访谈获得数据；以及3)大量的“未经治疗/最低限度治疗”患者(n=208)，从而为在中国的非急性、具有代表性的抽样“未经治疗和最低限度治疗组”中全面测试“虚证”亚型的有效性提供了独特的机会。我们首先试图在样本中确认一组“大量暴露于药物治疗”的精神病患者(即有精神科住院治疗的患者)的缺陷综合征结构，然后评估缺陷综合征在一组独特的“未经治疗或最低限度治疗”的精神病患者中的结构效度。我们的具体目标是：1)识别虚证病例，评估中国治疗的精神病患者虚证的结构效度，以确定该亚型与西方样本中已建立的关键人口学和临床变量是否具有相同的相关性模式。我们在所有分析中都对疾病的发育影响进行了控制。在《中国》中确认虚证在治疗组中的构念效度，将建立一个基线条件来检验目的#2)识别DS病例，并在未经治疗或经最低限度治疗的精神病患者组中评估虚证的构念效度，以确定该亚型与中国中的经治疗的精神病人组是否呈现出与关键的人口学和临床变量相同的相关模式。3)在全样本(n=389)中探索两个处理组之间的关系和关键结构效度变量是否在不同组之间的大小不同。为了模拟“缺陷综合征分类”X“治疗组状态”的统计交互作用，我们将检验我们用来证明DS和非DS之间的结构有效性的变量的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来建立缺陷综合征的结构有效性的研究，从而在一个具有代表性的、非西医基础的样本中控制急性精神病、药物使用和验证缺陷综合征。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，从而为未来精神分裂症的病因学、遗传连锁和干预研究做出贡献。这笔R03(小额拨款)将是哥伦比亚大学全球精神健康计划提出的几项建议中的第一项，该计划将启动一个新颖而富有成效的研究计划，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，以检查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.