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

检查中国未经治疗的代表性 SCZ 队列中的缺陷综合症

基本信息

批准号：
8311054
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
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-05 至 2014-04-30
项目状态：
已结题

项目摘要

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.

描述（申请人提供）：精神分裂症综合征中不同疾病“亚型”或“中间表型”的识别将有助于未来的病因学研究、显着基因和生物标记物的识别，并实现更有效的预防和干预。一个有希望的精神分裂症“亚型”，“缺陷综合征”（DS），其特征是持续性和原发性阴性症状。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、对结果的预测能力和特定的风险因素。虽然大量的文献支持区分“赤字”从“非赤字”综合征精神分裂症，有一个重要的差距的证据，这一建议试图解决。研究的方法论问题和地理限制使研究人员无法完全回答关于这种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，没有任何研究有效地排除了急性精神病和长期药物治疗在评估缺陷综合征中的影响。本提案旨在通过对唯一现有的代表性、非急性、基于人群的“未经治疗或最低限度治疗”的精神分裂症患者样本进行二次数据分析来解决这一差距，这些样本是从非西方背景下（中国）的一项里程碑式精神病学流行病学研究中获得的。利用这种基于人群的慢性未经治疗的精神病样本-平均10.5年未经治疗的疾病，因此可能具有明显的临床特征，如更大的精神病-为缺陷综合征的结构效度提供了一个非凡的测试。我们建议使用的代表性样本389例诊断为精神障碍的患者从中国4个省的分层随机抽样（抽样框架为1.13亿成年人）。与以往的研究相比，该样本具有以下独特优势：1）样本量大（n=389）; 2）具有代表性，基于人群的抽样，通过临床医生管理的访谈获得数据;和3）大量“未治疗/最低限度治疗”的患者（n= 208），因此提供了一个独特的机会来全面测试“缺陷综合征”亚型在非急性，在中国代表性抽样的“未治疗和最低治疗组”。我们首先试图在一组精神病患者中确认缺陷综合征的结构，在这个样本中“基本上暴露于药物治疗”（即，有1精神病住院治疗），然后在一个独特的“未经治疗或最低限度治疗”的精神病患者组中评估缺陷综合征的结构效度。我们的具体目标是：1）识别缺陷综合征的病例，并评估缺陷综合征在中国“治疗”的精神病患者中的结构效度，以确定该亚型是否与西方样本中已经建立的关键人口统计学和临床变量表现出相同的相关性模式。我们在所有分析中控制了疾病对发育的影响。验证中国治疗组中缺陷综合征的结构效度将建立基线条件以检验目标2。2)识别DS病例并评估“未经治疗或最低限度治疗”的精神病患者组中缺陷综合征的结构效度，以确定该亚型与中国“治疗”组中关键人口统计学和临床变量的相关性是否相同。3)在全样本（n= 389）中探索两个治疗组与关键结构验证变量之间的关系是否存在组间差异。为了模拟“缺陷综合征分类”X“治疗组状态”的统计学相互作用，我们将检查用于证明DS和非DS之间的结构效度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建立缺陷综合征结构效度的研究，从而控制急性精神病，暴露于药物使用，并在一个代表性的，非西方的样本中验证缺陷综合征。这项研究有希望提供证据的缺陷综合征作为一个独特的疾病“亚型”内精神分裂症，从而有助于未来的病因学，遗传连锁和精神分裂症的干预研究。这项R 03（小额赠款）将是哥伦比亚全球精神卫生计划的几项建议中的第一项，该计划将启动一项新颖而富有成效的研究计划，研究非西方社会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。