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Cardiac autonomic dysfunction of patients with schizophrenia

精神分裂症患者心脏自主神经功能紊乱

基本信息

批准号：
326337412
负责人：
Professor Dr. Karl-Jürgen Bär
金额：
--
依托单位：
Klinik für Psychiatrie und Psychotherapie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2021-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/326337412?language=en
关键词：
Cardiac autonomic dysfunction patients schizophrenia

项目摘要

Patients with schizophrenia have a shortened life expectancy of about 15-20 years. Beyond the effects accounted for by lifestyle and antipsychotic medication, several lines of evidence indicate a shared underlying pathophysiology of cardiac conditions and schizophrenia. One of the most striking cardiac peculiarities is the pattern of profound cardiac autonomic dysfunction (CADF) described in unmedicated patients with schizophrenia and healthy relatives, which is known to contribute to sudden cardiac events.This grant application aims to investigate two separate patient groups suffering from schizophrenia as well as healthy controls. One group with severe cardiac autonomic dysfunction (sCADF), associated with low vagal activity and high sympathetic modulation, and a second group with absent cardiac autonomic dysfunction (aCADF. In all subjects, possible long-term consequences of CADF for cardiac function, cognition and the underlying brain structure will be investigated. At the level of the heart, an echocardiography investigation will be performed to analyze whether severe CADF is in fact associated with distinct functional changes of the heart (subclinical diastolic dysfunction). In addition, assumed risk markers for life-threatening arrhythmias will be exploited to identify de- and repolarization abnormalities (e.g. T-wave alternans or QT variability). In healthy subjects, high vagal activity is associated with superior cognitive functioning and reduced cardiac vagal modulation impacts on cognitive performance. At the level of the brain, we assume that sCADF is associated with distinct neuropsychological deficits and neurostructural abnormalities in the brain of patients with schizophrenia as a consequence of reduced vagal functioning. This will be investigated using neuropsychological testing and the application of a structural magnetic resonance imaging (MRI) to investigate the gray matter abnormalities and the diffusion tensor imaging (DTI) to investigate the white matter integrity.We expect that answering the main questions of this grant application will provide a basis for (1) identifying patients who are at risk for cardiac events and (2) will elucidate some important pathophysiological mechanisms. Identifying neurostructural abnormalities and impaired cognition in sCADF patients might additionally help to develop preventive strategies. If a close relation between CADF and impaired cognitive functioning might be present in a subset of patients, physical activity might be the intervention of choice to improve both CADF and cognition.

精神分裂症患者的预期寿命缩短约15-20年。除了生活方式和抗精神病药物的影响外，一些证据表明心脏病和精神分裂症有共同的潜在病理生理学。其中最引人注目的心脏特点是深刻的心脏自主神经功能障碍（CADF）的模式中描述的未经药物治疗的精神分裂症患者和健康的亲属，这是已知的，有助于突发cardiac events.This拨款申请旨在调查两个独立的患者群体患有精神分裂症以及健康对照。一组有严重的心脏自主神经功能障碍（sCADF），与低迷走神经活动和高交感神经调制相关，第二组没有心脏自主神经功能障碍（aCADF）。在所有受试者中，将研究CADF对心脏功能、认知和潜在脑结构的可能长期后果。在心脏水平，将进行超声心动图检查，以分析重度CADF实际上是否与心脏的明显功能变化（亚临床舒张功能障碍）相关。此外，将利用危及生命的心律失常的假定风险标志物来识别去极化和复极异常（例如，T波交替或QT变异性）。在健康受试者中，高迷走神经活动与上级认知功能相关，心脏迷走神经调节对认知表现的影响降低。在大脑水平，我们假设sCADF与精神分裂症患者大脑中的神经心理缺陷和神经结构异常相关，这是迷走神经功能降低的结果。这将通过神经心理学测试和结构磁共振成像（MRI）的应用来研究灰质异常和扩散张量成像（DTI）的应用来研究白色物质的完整性。我们希望回答这个拨款申请的主要问题将为（1）识别有心脏事件风险的患者和（2）将阐明一些重要的病理生理机制。识别sCADF患者的神经结构异常和认知受损可能有助于制定预防策略。如果CADF和认知功能受损之间的密切关系可能存在于一个子集的患者，体力活动可能是选择的干预措施，以改善CADF和认知。