Grant-Funded Projects on Affective Disorders

Clinician-Scientist Programme "Understanding InterOrgan Networks in Cardiac and Vascular Diseases (Union-CVD)"

Project leader: Prof. Dr. Stefanie Hahner
Project leader psychiatry: Prof. Dr. Jürgen Deckert
Project duration: 2019-2021

The mission of the Clinician-Scientist Programme (CSP) "Understanding of InterOrgan Networks in Cardiac and Vascular Diseases" (UNION-CVD) is to systematically develop and support highly talented young Clinician Scientists (CSs) within a structured programme by taking advantage of the existing excellent scientific environment in the field of cardiac and vascular research in Würzburg.

Subproject "Brain"

We have a long-standing research interest in the interaction between the cardiovascular system and the brain. Vascular diseases affect the brain, and the brain is particularly sensitive to deprivation of oxygen, initiating a complex bilateral relationship between cardiovascular and cerebrovascular disease. On the other hand, brain diseases via activation of the sympathetic nervous system and the hypothalamic–pituitary–adrenal (HPA)-axis can influence cardiac and vascular function.

We are currently performing several clinical research projects and studies in which CSs can actively take part comprising for example:

Stroke:TRANSIT-Stroke (telemedical stroke network in the region of Lower Franconia; cooperation between Neurology, Epidemiology, Neuroradiology); SICFAIL (prevalence and natural course of cardiac dysfunction and long-term vascular comorbidities and complications in ischemic stroke patients; cooperation between Cardiology, Neurology, Epidemiology); INSU-COR (case-control study on the role of the insular cortex for cardiovascular complications in ischemic stroke; cooperation between cardiology, neurology, neuroradiology, and epidemiology). These projects will serve as research platforms for CSs to develop interdisciplinary projects to assess the bidirectional link between cardiac disease (e.g. heart failure, arrhythmia, coronary heart disease) and cerebrovascular diseases regarding pathophysiology, occurrence and further course through improved diagnostics and interventions.

Endovascular acute stroke treatment has been recently established as the single most effective acute form of therapeutic stroke intervention with level 1A evidence. The immediate temporal contingency between the cerebral ischemic index event (embolic occlusion), the acute therapeutic index event (the restoration of blood flow by endovascular recanalization), and their effect on cardiac rhythm and electric function is one of the most important aspects in probing the causality of insular brain function for regulating the cardiac autonomic nervous system. This will be investigated in more detail (cooperation between Neuroradiology, Neurology, Cardiology).

Cognition: Cognition.Matters-HF is a longitudinal cohort study that completed recruitment and currently undertakes its 5-year follow-up investigation. Patients with heart failure have been comprehensively phenotyped by standardized cardiac and neurologic examinations, sophisticated neuropsychological testing, multiparametric 3T MRI of the brain, and were iteratively seen after 1, 3 and 5 years (cooperation with Neurology, Neuroradiology, Cardiology, Psychology, Psychiatry, CHFC). Preliminary data reveal that cognition affects therapeutic outcome and future studies should be performed integrating cognitive function in therapeutic algorithms of heart failure. A CS will work here in the 5-year follow-up and associated analyses of clinical, imaging and biomaterial data.

Depression: DaCFail and Insu-DacFail are complementary projects designed as clinical observational studies to define mechanistic links between depression and HF with a focus on sympathotonus, HPA axis and inflammation, including analyses of insular cortex function utilizing functional 3T MRI (cooperation between Psychiatry, Cardiology, Neuroradiology, CHFC). Outcomes of these and similar studies in Cardiosurgery will define depressed patients at risk for developing heart disease and possible mechanisms providing further rationale for clinical studies. The CS will analyze the data to define these subgroups.

Anxiety: In clinical therapeutic trials conducted within the Panic-Net we demonstrated that vagal tonus affects therapeutic outcome in panic disorders. In animal models we are probing the effect of fear network activity on heart function using optogenetics 14, 15. The CS will help to establish this model in a cardiovascular context and thereby evaluate the interaction between specific brain circuits and cardiovascular diseases. Follow-up studies should translate these observations into innovative and individualized therapeutic approaches based on heart function.

Recently, we established a joint platform based on the methodology and instruments developed within the prospective population-based STAAB cohort study (n=5,000) allowing the characterization of patients clinically, psychometrically, and state-of-the-art echocardiography. STAAB includes a repetitive follow-up in 5-year intervals. Morphologic as well as functional MRI imaging modalities for heart and brain function will become available in parallel. The CS can evaluate which psychometric parameters are associated with prevalent and incident cardiac diseases.