Cardiac autonomic dysfunction of patients with schizophrenia

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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.