COH-FIT

This is the worldwide greatest study for the examination of health consequences during the COVID-pandemic. More than 100,000 participants from >180 countries were asked to fill in a questionnaire for the assessment of mental disorders. The Hannover Medical Schools specifically targets patients with cardiovascular disorders, and with post-traumatic stress disorders.

Publications:

• Kai G Kahl, Christoph U Correll: Management of Patients With Severe Mental Illness During the Coronavirus Disease 2019 Pandemic. JAMA Psychiatry 2020;77:977-978. DOI

We examine the brain-heart-relationship in several studies using cohorts of well-characterized patients: Body-composition as a marker of diabetes risk and cardiovascular risk is studied in the EAT-project("Epicardial Adipose Tissuein patients with major depressive disorder and comorbidities"). We demonstrated epicardial adipose tissue as an important biomarker for cardiovascular risk in depressed patients, and in patients with adult congenital heart disease and comorbid major depressive disorder. We further demonstrated in a randomized-controlled study that the amount of epicardial adipose tissue is reduced during a structured exercise intervention, in parallel with the cardiovascular risk reduction.

The prevalence of mental disorders is studied in two ongoing projects using well characterized cohorts of patients with adult congenital heart disease(PsychOnHeart) and patients with pulmonary arterial hypertension(PEPPAH). The prevalence of major depression and anxiety disorders is increased in both adults with congenital heart disease (ACHD) and in patients with pulmonary arterial hypertension. Further, major depression is associated with increased mortality in ACHD patients.

Our projects are performed in close cooperation to several Departments and Institutes of Hannover Medical School, i.e.

• Dep. of Cardiology and Angiology (Prof. Dr. Johann Bauersachs, PD Dr. Mechthild Westhoff-Bleck),
• Dep. of Pulmology and Allergology (Prof. Dr. Marius Höper, Prof. Dr. Karen Olsson), and
• the Institute of Diagnostic and Interventional Radiology (Prof. Dr. Dagmar Hartung).

The complete list of collaborators is given at the end of the text.

Selected publications:

• Pfeffer TJ, Herrmann J, Berliner D, König T, Winter L, Ricke-Hoch M, Ponimaskin E, Schuchardt S, Thum T, Hilfiker-Kleiner D, Bauersachs J, Kahl KG. Assessment of major mental disorders in a German peripartum cardiomyopathy cohort. ESC Heart Fail. 2020. 10. doi: 10.1002/ehf2.12967. DOI
• Stubbs B, Vancampfort D, Hallgren M, Firth J, Veronese N, Solmi M, Brand S, Cordes J, Malchow B, Gerber M, Schmitt A, Correll CU, De Hert M, Gaughran F, Schneider F, Kinnafick F, Falkai P, Möller HJ, Kahl KG. EPA guidance on physical activity as a treatment for severe mental illness: a meta-review of the evidence and Position Statement from the European Psychiatric Association (EPA), supported by the International Organization of Physical Therapists in Mental Health (IOPTMH). Eur Psychiatry. 2018;54:124-144. DOI
• Kahl KG, Kerling A, Tegtbur U, Gützlaff E, Herrmann J, Borchert L, Ates Z, Westhoff-Bleck M, Hueper K, Hartung D. Effects of additional exercise training on epicardial, intra-abdominal and subcutaneous adipose tissue in major depressive disorder: A randomized pilot study. J Affect Disord. 2016;192:91-7. DOI

Background

An adequate supply and use of glucose by the brain is essential for the maintenance of normal brain function. Disturbances in cerebral glucose metabolism in the context of psychiatric diseases and under psychopharmacological therapies found in imaging studies could therefore be an integral part of the pathophysiological process underlying psychiatric diseases. Against this background, studies investigating glucose uptake and function of the cerebral glucose transporters GLUT1 and GLUT3 at the cellular level are missing.

Psychiatric diseases

In a first study we could show that the methylation of GLUT1 measured in the blood of depressed patients was significantly increased and normalized depending on the success of therapy (1).

Psychopharmacological therapy

Ex vivo studies in peripheral blood mononuclear cells (PBMC) showed that stimulation with different psychotropic drugs differentially regulates cellular glucose uptake. While the antipsychotic olanzapine inhibits glucose uptake, stimulation with both the antipsychotic arippriprazole and the antidepressant fluoxetine resulted in an increase in glucose uptake. Since the changes in glucose uptake were independent of the protein content of GLUT1 and GLUT3, it seems likely that the functionality of glucose transporters is not exclusively regulated at the level of protein expression (2, 3). The finding that fluoxetine stimulation significantly increased protein palmitoylation of both glucose transporters corroborates a potential posttranslational regulation of glucose transporters (3).

Perspective

Since palmitoylation was shown to be involved in the functional regulation of integral membrane proteins, we plan to investigate in future studies the underlying molecular mechanisms of GLUT1 and GLUT3 palmitoylation and their functional consequences in in vitro and in vivo approaches in the context of depression and antidepressant therapy.

Publications:

• Kahl KG, Georgi K, Bleich S, Muschler M, Hillemacher T, Hilfiker-Kleinert D, et al. Altered DNA methylation of glucose transporter 1 and glucose transporter 4 in patients with major depressive disorder. Journal of psychiatric research. 2016;76:66-73. DOI
• Stapel B, Kotsiari A, Scherr M, Hilfiker-Kleiner D, Bleich S, Frieling H, et al. Olanzapine and aripiprazole differentially affect glucose uptake and energy metabolism in human mononuclear blood cells. Journal of psychiatric research. 2017;88:18-27. DOI
• Stapel B, Gorinski N, Gmahl N, Rhein M, Preuss V, Hilfiker-Kleiner D, et al. Fluoxetine induces glucose uptake and modifies glucose transporter palmitoylation in human peripheral blood mononuclear cells. Expert opinion on therapeutic targets. 2019;23(10):883-91. DOI

There are various psychotherapeutic methods for the treatment of mental disorders, which have convincingly proven their clinical effectiveness. However, it remains unclear to date which neurobiological changes are associated with psychotherapeutic improvements, and which neurophysiological factors can predict treatment success. We aim to answer this question with a series of scientific studies, such as "Neurobiological foundations of psychotherapy"(neuroGap).

As part of a national, DFG-funded, multicenter clinical study titled "Cognitive Behavioral Analysis System of Psychotherapy (CBASP) vs. Behavioral Activation (BA) in inpatients with persistent depressive and therapy-resistant disorders: effectiveness, moderators and mediators of change "(PI: Prof. Dr. Eva-Lotta Brakemeier, University of Greifswald) the MHH is participating in a clinical intervention study on the effectiveness of two psychotherapy methods for persistent depression (changePDD). The study is financed with a total of over € 1,700,000 and tries to examine the effectiveness of these two psychotherapy methods as well as the moderators and mediators of any psychotherapy improvements. One research aim is to investigate whether after 16 weeks of treatment there will be a significant superiority in the CBASP group over the BA group. In addition, this study aims to find out which intervention is most suitable for which patient and which factors cause therapeutic success.

E.g., as part of moderator analyzes, this study aims to answer whether early traumatic childhood experiences and the methylation of exon IV of the BDNF gene have an influence on the differential effectiveness of the two treatments. Mediator analyzes are used to check whether the symptom improvements can be explained by improvements in the interpersonal problems in CBASP and an increase in the level of activity in BA.

A follow-up survey after 48 weeks will provide valuable data regarding the sustainability of therapeutic improvements. Finally, the health economic potential of the interventions is examined with the help of cost-benefit analyzes in order to provide important information on the cost-effectiveness of an implementation in routine care. In an additional attempt to understand the neurobiological underpinnings of psychotherapy, changePDD_mMRI is performed. Although psychotherapy is considered the treatment of first choice for many psychopathologies, it is still insufficiently known which neurobiological and neurophysiological changes and mechanisms of change are associated with or cause clinical improvements. Our research on this topic aims to find brain markers as well as heartmarkers for psychopathologies such as depression and determine changes in these markers during psychotherapeuty. As an addition to the changePDD study, it is planned to determine the neurobiological and psychophysiological change mechanisms of change for the two examined psychotherapy methods (CBASP and BA) for the first time in a substantial sample of N> 400 subjects and with the help of a longitudinal study design. The data collected in this way should enable us to develop markers for psychotherapeutic improvements, for predicting psychotherapeutic success and for determining an optimal psychotherapy plan.

Publications:

• Heitland I, Barth V, Winter L, Jahn N, Burak A, Sinke C, Krüger THC, Kahl KG. One Step Ahead-Attention Control Capabilities at Baseline Are Associated With the Effectiveness of the Attention Training Technique. Front Psychol. 2020;11:401. DOI
• Barth V, Heitland I, Kruger THC, Kahl KG, Sinke C, Winter L. Shifting Instead of Drifting - Improving Attentional Performance by Means of the Attention Training Technique. Front Psychol. 2019;10:23. DOI

• Institute for Neurophysiology (Prof. Dr. Evgeni Ponimaskin)
• Institute for Translational Therapy Strategies (Prof. Dr. Thomas Thum)
• Department for Cardiology (PD Dr. Mechthild Westhoff-Bleck)
• Department for Pulmology (Prof. Dr. Marius Höper, Prof. Dr. Karen Olsson)
• Institute for Sports Medicine (Prof. Dr. Uwe Tegtbur)
• Institute for Diagnostic and Interventional Radiology (Prof. Dr. Dagmar Hartung)
• Institute for Diagnostic and Interventional Neuroradiology (Prof. Dr. Dr. Xiaoxi Ding)
• Clinic for Ginecology and Obstetrics (Prof. Dr. Ralf Hass)
• Clinical Psychology and Sexual medicine (Prof. Dr. Tillmann Krüger)

• Central Institute for Mental Health, Mannheim (Prof. Dr. Michael Deuschle)
• University Medical Center Schleswig-Holstein, Lübeck Campus (Prof. Dr. Ulrich Schweiger, Prof. Dr. Phillip Klein)
• Charité University Medicine (Prof. Dr. Christian Otte, Prof. Dr. Christoph Correll, Prof. Dr. Philipp Sterzer)
• University of Greifswald (Prof. Dr. Eva-Lotta Brakemeier, Dr. Jan Richter)
• LMU Munich Clinic (Prof. Dr. Frank Padberg, Prof. Dr. Katja Bertsch, Dr. Daniel Keeser)
• University Hospital Tübingen (Prof. Dr. Thomas Ethofer)
• University Hospital Marburg (Prof. Dr. Benjamin Straube)

• Norwegian University of Science and Technology, Trondheim, Norway (Prof. Dr. Hans Nordahl)
• University of Manchester (Prof. Dr. Adrian Wells)
• Altrecht Academic Anxiety Center, Utrecht, the Netherlands (Dr. Puck Duits)
• Altrecht Academic Anxiety Center, Utrecht, the Netherlands (Dr. Suzy J.M.A. Matthijssen)
• Autonomous University of Barcelona, Barcelona, Spain (Dr. Miguel A. Fullana)
• Karolinska Institutet, Stockholm, Sweden (Dr. Armita Golkar)
• KU Leuven, Leuven, Belgium (Prof. Dr. Bram Vervliet)
• Leiden University, Leiden, the Netherlands (Dr. Peter Bos)
• Meander Medical Center, Amersfoort, Netherlands (Dr. Liselotte C.M. Verhoeven)
• University of Amsterdam, the Netherlands (Hannah Spencer)
• Utrecht University, Utrecht, the Netherlands (Dr. Estrella Montoya)
• Utrecht University, Utrecht, the Netherlands (Dr. Iris Schutte)
• Utrecht University, Utrecht, the Netherlands (Prof. Dr. Danielle C. Cath)
• Utrecht University, Utrecht, the Netherlands (Prof. Dr. Joke Baas)
• Utrecht University, Utrecht, the Netherlands (Prof. Dr. Leon Kenemans)
• Utrecht University, Utrecht, the Netherlands (Prof. Dr. Marcel A. van den Hout)
• Utrecht University, Utrecht, the Netherlands (Prof. Dr. Susan Branje)

Phone: +49 511 532 3559 / 7367

Fax: +49 511 532 7375

heitland.ivo-aleksander@mh-hannover.de

Research focus: Neurobiology of psychotherapy, psychophysiology, neuroscience

Title of the PhD-thesis: "Born to be afraid? The neurogenetics of fear and punishment processing"

Publications: Pubmed

Phone: +49 511 532 7245

Fax: +49 511 532 7276

stapel.britta@mh-hannover.de

Research focus:

• Cellular energy metabolism
• Glucose transporter

Title of the PhD thesis: "Impact of myocardial STAT3 deficiency on the heart under chronic activation of neurohumoral systems"

Excellence at a glance:

• Rudi-Busse-Young Investigator Award for experimental cardiovascular research (2015)
• Project funding by the MHH's internal university funding program "HiLF" ('Hochschulinterne Leistungsförderung', 2017)
• Award of the German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology (DGPPN, 2019)

Publications: Pubmed

caldarone.flora@mh-hannover.de

Research focus: Psychiatric Neurosciences

Title of the doctoral thesis: official title: 'Neurocognitive changes induced by the Attention Training Technique - a placebo-controlled, randomized double-blind study in healthy individuals and patients with borderline personality disorder'

English translation: 'Neurocognitive changes induced by the Attention Training Technique - a placebo-controlled, randomized, double-blind study in healthy subjects and patients with borderline personality disorder'

gebhardt.philippa@mh-hannover.de

Research focus: Psychiatric Neurosciences

Title of the doctoral thesis: official title: 'Neurophysiological changes induced by the Attention Training Technique - a placebo-controlled, randomized double-blind study in healthy individuals and patients with borderline personality disorder'

English translation: 'Neurophysiological changes induced by the Attention Training Technique - a placebo-controlled, randomized, double-blind study in healthy subjects and patients with borderline personality disorder'