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Biomarkers and Mechanisms of Stress Pathophysiology in Early Schizophrenia

早期精神分裂症应激病理生理学的生物标志物和机制

基本信息

批准号：
9891098
负责人：
Joshua Chiappelli
金额：
$ 19.08万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-01 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9891098
关键词：
Acute Adrenal Glands Age of Onset Ambulatory Care Facilities Anterior Antipsychotic Agents Area Behavioral Biochemical Biological Biological Markers Brain Caring Chronic Disease Clinical Clinical Investigator Clinical Research Cognitive deficits Collaborations Data Development Disease Education Enzymes Exhibits Exposure to Female Functional disorder Glucocorticoids Glutamates Goals Health Hormones Human Hydrocortisone Hypothalamic structure IL6 gene Immune Immune response Individual Inflammation Inflammatory Inflammatory Response Interleukin-6 Intervention Investigation Kynurenic Acid Laboratories Lead Link Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Maryland Measurement Measures Mediating Mental disorders Mentors Mentorship NMDA receptor antagonist Pain Pathway interactions Patients Peripheral Pilot Projects Pituitary Gland Principal Investigator Process Protons Psychological Stress Psychotic Disorders Public Health Research Research Personnel Research Project Grants Role Saliva Sampling Schizophrenia Sex Differences Stress Symptoms System Testing Training Tryptophan Tryptophan Metabolism Pathway Universities base biological adaptation to stress cingulate cortex cytokine experimental study functional outcomes gender difference glutamatergic signaling hypothalamic-pituitary-adrenal axis inflammatory marker medical schools neuroimaging neuroimmunology novel pre-clinical research programs psychological stressor receptor research study response skill acquisition stress reactivity stressor translational study

项目摘要

Abstract Stress is a major factor contributing to development of psychiatric disorders, including schizophrenia. Previous studies have revealed possible abnormalities in the hypothalamic- pituitary-adrenal (HPA) axis in schizophrenia, with evidence that schizophrenia patients show abnormal levels of cortisol, the main stress hormone, in response to stress . Cortisol primes the body to respond to stress, but also suppresses inflammatory activity that could be detrimental to health. There is increasing evidence that schizophrenia is characterized by a state of low-grade inflammation, though the origin and consequences of this inflammation are unknown. Both cortisol and inflammatory markers may have effects on the brain, and conversely, the brain may exert top-down control over cortisol and immune responses to stress. This K23 mentored clinical research project, submitted by Principal Investigator Dr. Joshua Chiappelli, will compare individuals with schizophrenia to healthy controls in how they respond to laboratory based stressful challenges, including a psychological stressor and a somatic stressor that involves exposure to pain. Levels of cortisol and IL-6 will be measured in saliva samples collected before and after these stress challenges to examine if schizophrenia patients have an abnormality in the normal suppression of inflammation by cortisol. Levels of glutamate in the brain will be examined with magnetic resonance spectroscopy (MRS) concurrently with cortisol and IL-6 to test if peripheral responses to stress are modulated by the brain. This project will take place at the Maryland Psychiatric Research Center (MPRC), part of the University of Maryland School of Medicine. The MPRC operates several outpatient clinics specializing in care of schizophrenia patients as well as a MR imaging center; the research programs of the MPRC include preclinical and clinical research studies focusing on the causes, course, and treatment of schizophrenia. The K23 proposal also includes a comprehensive training plan to facilitate Dr. Chiappelli’s development into an independent clinical researcher. Mentorship will be provided by Dr. Elliot Hong, an expert in schizophrenia and neuroimaging; Dr. Laura Rowland, an expert in use of magnetic resonance spectroscopy in schizophrenia; Dr. Leonardo Tonelli, an expert on neuroimmunology; and Dr. Diana Fishbein, an expert on stress and development. This project will provide preliminary data for further R01 investigations into the mechanisms of stress pathophysiology in schizophrenia and will provide Dr. Chiappelli with the necessary education and skill development to lead further translational studies as an independent clinical investigator.

摘要压力是导致精神障碍发展的一个主要因素，包括精神分裂症。此前的研究显示，下丘脑可能存在异常-- 精神分裂症患者的垂体-肾上腺(HPA)轴应激时，主要应激激素皮质醇的异常水平。皮质醇使身体对压力做出反应，但也抑制可能对身体有害的炎症活动健康。越来越多的证据表明，精神分裂症的特点是处于一种低度状态炎症，尽管这种炎症的起源和后果尚不清楚。两者都有皮质醇和炎症标志物可能对大脑有影响，反之，大脑可能对皮质醇和对压力的免疫反应进行自上而下的控制。这位K23指导首席研究员Joshua Chiappelli博士提交的临床研究项目将比较精神分裂症患者与健康对照组在实验室基础上的反应应激性挑战，包括心理压力源和躯体压力源暴露在痛苦中。将在之前收集的唾液样本中测量皮质醇和IL-6的水平在这些压力挑战之后，检查精神分裂症患者是否在皮质醇对炎症的正常抑制。大脑中的谷氨酸水平将是用磁共振波谱(MRS)与皮质醇和IL-6同时检查测试外周对压力的反应是否受到大脑的调节。该项目将在马里兰精神病学研究中心(MPRC)，马里兰大学医学院的一部分医学。精神分裂症防治中心开设了几家专门治疗精神分裂症的门诊诊所。患者和磁共振成像中心；MPRC的研究项目包括临床前以及侧重于精神分裂症的病因、病程和治疗的临床研究。 K23提案还包括一项全面的培训计划，以促进Chiappelli博士发展成为独立的临床研究人员。指导将由埃利奥特博士提供洪，精神分裂症和神经成像专家；劳拉·罗兰博士，使用精神分裂症的磁共振波谱；莱昂纳多·托内利博士，神经免疫学；以及压力和发育专家戴安娜·菲什贝因博士。这个项目将为R01对应激机制的进一步研究提供初步数据精神分裂症的病理生理学，并将为Chiappelli博士提供必要的教育和技能发展，作为独立的临床研究领导进一步的翻译研究调查员。