Cardiac autonomic dysfunction of patients with schizophrenia

精神分裂症患者的预期寿命缩短了约15-20年。除了生活方式和抗精神病药物的影响外，有几条证据表明，心脏疾病和精神分裂症有共同的潜在病理生理学。最显著的心脏特征之一是在未服用药物的精神分裂症患者和健康亲属中描述的严重心脏自主神经功能障碍(CADF)的模式，这被认为是导致突发心脏事件的原因。这项拨款申请旨在调查两个不同的精神分裂症患者组和健康对照组。一组严重心脏自主神经功能障碍(SCADF)，伴随迷走神经活动减少和交感神经高度调节；第二组缺失性心脏自主神经功能障碍(ACADF)。在所有受试者中，将调查CADF对心脏功能、认知和潜在的大脑结构可能产生的长期后果。在心脏层面，将进行超声心动图检查，以分析严重的CADF是否确实与心脏明显的功能变化(亚临床舒张期功能障碍)有关。此外，将利用假定的危及生命的心律失常的风险标记物来识别除极和复极异常(例如T波交替或QT变异性)。在健康受试者中，高迷走神经活动与更好的认知功能和减少心脏迷走神经调节对认知表现的影响有关。在大脑水平上，我们假设sCADF与精神分裂症患者脑部明显的神经心理缺陷和神经结构异常有关，这是迷走神经功能下降的结果。这将通过神经心理测试和应用结构磁共振成像(MRI)来研究灰质异常和扩散张量成像(DTI)来研究白质完整性。我们预计，回答这项赠款申请的主要问题将为(1)识别有心脏事件风险的患者提供基础，(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还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组患者中，那么体力活动可能是改善CADF和认知的首选干预措施。

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.