A Potential State and Relapse Predictive Marker in Schizophrenia

精神分裂症的潜在状态和复发预测标记

• 批准号: 8354551
• 负责人: Brian James Miller
• 金额: $ 18.42万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8354551
• 关键词: Acute; Affect; Alcohol or Other Drugs use; Anti-Inflammatory Agents; Anti-inflammatory; Antipsychotic Agents; Award; Blood specimen; Brain; CD14 gene; Cells; Chronic; Chronic Disease; Clinical; Cognition; Comorbidity; Complex; Cross-Sectional Studies; Data; Development Plans; Disease; Double-Blind Method; Encephalitis; FCGR3B gene; Family; Functional disorder; Funding; Future; Goals; Hippocampus (Brain); Immune; Immunology; Impaired cognition; Individual; Inflammation; Injectable; Interleukin-2; Interleukin-6; Knowledge; Kynurenic Acid; Lead; Left; Leukocytes; Life; Longitudinal Studies; Lymphocyte Subset; Marijuana Abuse; Marijuana Dependence; Marijuana Smoking; Measures; Mentored Patient-Oriented Research Career Development Award; National Institute of Mental Health; Oral; Outcome Measure; Outpatients; Participant; Patients; Pharmaceutical Preparations; Physicians; Psychopathology; Psychotic Disorders; Randomized; Recurrence; Regulatory T-Lymphocyte; Relapse; Research; Resistance; Role; Sampling; Schizophrenia; Scientist; Serum; Strategic Planning; Study of serum; Symptoms; Techniques; Testing; Therapeutic Intervention; Thinking; Time; TimeLine; Treatment Effectiveness; Tryptophan; Writing; adverse outcome; base; career; career development; cytokine; design; disorder later incidence prevention; experience; functional disability; improved; monocyte; novel; patient oriented research; prevent; primary outcome; public health priorities; response; skills; skills training

DESCRIPTION (provided by applicant): My career development goal during this Mentored Patient-Oriented Research Career Development Award (K23) is to obtain the skills and training needed to become an independent physician-scientist in patient-oriented research in the immunology of schizophrenia. The Career Development Plan will focus on: 1) increasing my knowledge of monocyte and T-helper lymphocyte subsets, 2) developing an understanding of and experience with modern techniques in immunological research, 3) increasing my knowledge and skills in the design, conduct, and analysis of longitudinal studies, 4) developing a greater understanding and experience with relapse in schizophrenia research, and 5) honing my skills in critical thinking, scientific writing, and presentation. I will apply this knowledge to patient-orinted research to advance our understanding of the pathophysiology and potentially the treatment of relapse in schizophrenia. My research goal is to evaluate serum interleukin-6 (IL-6) levels as a potential clinical state and relapse predictive marker in schizophrenia using novel, complementary cross-sectional and longitudinal approaches. Project # 1 is a longitudinal study of serum IL-6 levels in participants in the NIMH-funded PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) study, a 30-month relapse prevention trial for which blood samples were drawn regularly, and relapse was the primary outcome measure. The primary goal is to determine if changes in serum IL-6 levels predict relapse. Project #2 is a cross-sectional study of serum IL-6 levels, tryptophan catabolites, and leukocyte subsets in relapsed and stable outpatients with schizophrenia, and controls. The primary goal is to evaluate serum IL-6 levels as a potential state marker for acute psychosis. A pathophysiological role for immune abnormalities in schizophrenia, including inflammation, was first hypothesized in 1967, and has been one of the more enduring findings in the field. Recently, increased understanding of the complex interactions between inflammation and the brain in other chronic diseases has better informed this relationship in schizophrenia. Moreover, several randomized, double-blinded trials found that adjunctive treatment with non-steroidal anti-inflammatory drugs (NSAIDs) significantly improved psychopathology in relapsed patients, and serum cytokine levels predicted response to NSAIDs. The confluence of these findings provides important empirical support for a pathophysiological role of inflammation in relapse in some patients with schizophrenia. This application promotes the NIMH Strategic Plan by exploring a novel potential marker for relapse in schizophrenia that could be used to assess treatment effectiveness, inform and advance relapse prevention efforts, and even help pave the way for future immune-based therapeutic interventions. PUBLIC HEALTH RELEVANCE: Schizophrenia is commonly a chronic, debilitating disorder with life-long consequences for affected individuals and families, and the clinical course is often characterized by recurrent relapses, which are associated with adverse outcomes, including increased treatment-resistant symptoms, cognitive decline, and functional disability. This Mentored Patient-Oriented Research Career Development Award (K23) will enable Dr. Brian Miller to further develop his career trajectory in schizophrenia research by exploring a novel potential clinical state and relapse predictive marker in schizophrenia. A better ability to understand and predict relapse in schizophrenia is a compelling opportunity and a public health priority.

描述（由申请人提供）：我在以患者为导向的研究职业发展奖（K23）期间的职业发展目标是获得成为精神分裂症免疫学以患者为导向的研究中的独立医师科学家所需的技能和培训。职业发展计划将侧重于：1) 增加我对单核细胞和辅助性 T 淋巴细胞亚群的了解，2) 加深对免疫学研究现代技术的理解和经验，3) 增加我在纵向研究的设计、实施和分析方面的知识和技能，4) 加深对精神分裂症研究复发的理解和经验，5) 磨练我在批判性思维、科学写作和演示方面的技能。我将把这些知识应用到以患者为导向的研究中，以增进我们对病理生理学和精神分裂症复发治疗的潜在理解。我的研究目标是使用新颖、互补的横断面和纵向方法来评估血清白细胞介素 6 (IL-6) 水平作为精神分裂症的潜在临床状态和复发预测标志物。项目 #1 是对 NIMH 资助的 PROACTIVE（口服抗精神病药物与注射药物疗效相比预防复发）研究参与者血清 IL-6 水平的纵向研究，这是一项为期 30 个月的复发预防试验，定期抽取血样，复发是主要结果指标。主要目标是确定血清 IL-6 水平的变化是否预示复发。项目 #2 是对复发和稳定的精神分裂症门诊患者和对照患者的血清 IL-6 水平、色氨酸分解代谢物和白细胞亚群进行的横断面研究。主要目标是评估血清 IL-6 水平作为急性精神病的潜在状态标志物。免疫异常（包括炎症）在精神分裂症中的病理生理作用最早于 1967 年被提出，并且一直是该领域最持久的发现之一。最近，人们对其他慢性疾病中炎症与大脑之间复杂相互作用的了解不断加深，更好地了解了精神分裂症中的这种关系。此外，几项随机、双盲试验发现，非甾体抗炎药 (NSAID) 辅助治疗可显着改善复发患者的精神病理学，血清细胞因子水平可预测对 NSAID 的反应。这些发现的结合为炎症在某些精神分裂症患者复发中的病理生理学作用提供了重要的经验支持。该申请通过探索精神分裂症复发的新型潜在标志物来促进 NIMH 战略计划，该标志物可用于评估治疗效果、告知和推进复发预防工作，甚至有助于为未来基于免疫的治疗干预措施铺平道路。 公共卫生相关性：精神分裂症通常是一种慢性、使人衰弱的疾病，对受影响的个人和家庭造成终生后果，临床病程通常是 其特点是反复复发，与不良后果相关，包括难治性症状增加、认知能力下降和功能障碍。这项以患者为导向的研究职业发展奖 (K23) 将使 Brian Miller 博士能够通过探索精神分裂症的新型潜在临床状态和复发预测标记，进一步发展他在精神分裂症研究方面的职业轨迹。更好地理解和预测精神分裂症复发的能力是一个令人信服的机会，也是公共卫生的优先事项。