COH-FIT survey

In order to understand the short and long-term effects of the coronavirus pandemic, scientists from all over the world have joined forces to conduct the world's largest study on the consequences of the coronavirus pandemic. The aim is to survey 100,000 people about their physical and mental well-being to find out how we can help those who need special support. In Hanover, patients with heart disease and trauma-related disorders are being studied in particular.

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

Several projects are investigating brain-heart interaction in large cohorts: The EAT ("Epicardial Adipose Tissuein patients with major depression and comorbidities") study looks at changes in body composition in patients with depression. The focus is on visceral (intra-abdominal) adipose tissue as a risk factor for the development of type 2 diabetes and epicardial adipose tissue as a risk factor for the development of coronary heart disease. It was shown for the first time that epicardial adipose tissue increases in depression and is suitable as a biomarker for cardiovascular risk in mental illness. Like the known risk factors (smoking, exercise, blood lipids), epicardial adipose tissue is sensitive to change and can be reduced through targeted exercise interventions.

In two other projects(PEPPAH, PsychOnHeart), the prevalence of mental illnesses and their influence on the risk of mortality are being investigated in cohorts of patients with congenital heart defects and pulmonary arterial hypertension that are unique in Germany. The prevalence of mental illness is increased in both diseases, and depression is a risk factor for premature mortality in patients with congenital heart disease.

These projects are being carried out in cooperation with the Clinical Departments of

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

 

Publications (selection):

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

 

Psychiatric diseases

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

 

Psychopharmacological therapy

Ex vivo studies in peripheral blood mononuclear cells (PBMC) showed that stimulation with various psychotropic drugs differentially regulates cellular glucose uptake. While the antipsychotic olanzapine inhibited glucose uptake, stimulation with both the antipsychotic arippriprazole and the antidepressant fluoxetine resulted in an increase in glucose uptake. Since the observed changes in glucose uptake occurred independently 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 confirms a potential post-translational regulation of glucose transporters (3).

 

Perspective

Since palmitoylation is involved in the functional regulation of integral membrane proteins, in future studies we plan to investigate underlying molecular mechanisms of GLUT1 and GLUT3 palmitoylation and their functional consequence 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

Various psychotherapeutic treatment methods exist for the treatment of mental disorders, which have convincingly demonstrated their clinical effectiveness. However, to date it remains unclear which neurobiological changes are associated with any psychotherapeutic improvements and which neurophysiological characteristics can predict treatment success. We are addressing this question with a series of scientific studies, including the neuroGap study(neurobiological mechanisms of psychotherapeutic processes).

As part of a national, DFG-funded multicenter clinical study entitled "Cognitive Behavioral Analysis System of Psychotherapy (CBASP) vs. Behavioral Activation (BA) in inpatients with persistent depressive and treatment-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 funded with a total of over €1,700,000 and is investigating the effectiveness of these two psychotherapy methods as well as the moderators and mediators of any psychotherapy improvements. Among other things, it is being investigated whether there will be a significant superiority in the CBASP group compared to the BA after 16 weeks of treatment. In addition, it will be investigated which intervention is most suitable for which patients and which factors determine therapeutic success.

For example, moderator analyses will be used to investigate whether early traumatizing childhood experiences and the methylation of exon IV of the BDNF gene have an influence on the differential efficacy of the two treatments. Mediator analyses will be used to examine whether the symptom improvements can be explained by improvements in interpersonal problems in CBASP and an increase in activity levels in BA.

A follow-up survey after 48 weeks will also provide valuable data on the sustainability of therapeutic improvements. Finally, the health economic potential of the interventions will be investigated using cost-benefit analyses to provide important information on the cost-effectiveness of implementation in routine care.

Although psychotherapy is considered the treatment of 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(changePDD_mMRI). Our research on this topic aims to identify brain markers and cardiac markers for psychopathologies such as depression and to determine their change through psychotherapeutic methods more precisely. As an addition to the changePDD study, it is therefore planned to determine the neurobiological and psychophysiological mechanisms of change of the two psychotherapy methods under investigation (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 the success of therapy and for determining the optimal therapy 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 of Neurophysiology (Prof. Dr. Evgeni Ponimaskin)
• Institute for Translational Therapy Strategies (Prof. Dr. Thomas Thum)
• Department of Cardiology (PD Dr. Mechthild Westhoff-Bleck)
• Department of Pulmonology (Prof. Dr. Marius Höper, Prof. Dr. Karen Olsson)
• Institute of Sports Medicine (Prof. Dr. Uwe Tegtbur)
• Institute of Diagnostic and Interventional Radiology (Prof. Dr. Dagmar Hartung)
• Institute of Diagnostic and Interventional Neuroradiology (Prof. Dr. Dr. Xiaoxi Ding)
• Clinical Department of Gynaecology and Obstetrics (Prof. Dr. Ralf Hass)
• Clinical Psychology and Sexual Medicine (Prof. Dr. Tillmann Krüger)

• Central Institute of 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 Klinikum Munich (Prof. Dr. Frank Padberg, Prof. Dr. Katja Bertsch, Dr. Daniel Keeser)
• Tübingen University Hospital (Prof. Dr. Thomas Ethofer)
• Marburg University Hospital (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 Centre, Utrecht, the Netherlands (Dr. Puck Duits)
• Altrecht Academic Anxiety Centre, 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 Centre, 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)