PD Dr. Dr. med. Martin E. Keck

 

Main Goals, Keywords

• Clinical Research: to evaluate the efficacy of algorithm-guided treatment in patients suffering from affective disorders and to provide new and evidence-based treatment guidelines to allocate health care resources efficiently in the acute and subacute care setting: The Zurich algorithm-guided treatment trial in depression and anxiety disorders
• Basic Research: to further investigate the intricate interaction of intracerebral hypothalamic-pituitary-adrenocortical (HPA) system regulation, emotionality and cognition in animal models for psychopathology
• to translate discoveries from basic research into clinical approaches

Group Members

1 group leader, 1 postdoctoral fellow, N.N. (PhD and MD students)

Previous and Current Research

Clinical Research: Affective disorders, such as depression and anxiety disorders are severe illnesses and the leading cause of disease-related disability among women. Among men, affective disorders are the second leading cause of disease-related disability, trailing only cardiovascular disease, which is a leading risk factor if occurring comorbidly with depression. Furthermore, depression appears to be a risk factor for coronary heart disease mortality, as a concurrent depressive disorder in cardiac patients increases the relative risk for subsequent mortality by a factor of three. Taken together, affective disorders are common, costly, and disabling conditions affecting up to 25% of the population. Depression and anxiety disorders, however, are recognized and diagnosed in only a small fraction of patients and an even smaller fraction of those identified receive appropriate pharmacological therapy. Moreover, health care providers are increasingly challenged by the increases in longevity with age representing a significant risk for the development of brain disorders. This project aims at both the improvement of pharmacotherapy and the refinement of endophenotypes underlying the heterogeneous group of depression and anxiety disorders in in- and outpatients. Importantly, an increased rate of cognitive impairment among the late-onset depressives supports the notion that some subgroups of late-onset depression might represent very early stages of dementia. To date, however, it remains unclear what predicts the putative progression into dementia and whether or not prophylaxis might be achievable. Collaborations exist with the Department of Psychiatry and Psychotherapy Charité, Berlin and within the Competence Nets in Medicine (Kompetenznetz Depression).

Basic Research: One of the research goals is the identification and characterisation of novel animal models for psychiatric diseases. Based on such animal models, we are engaged in evaluating neurobiological mechanisms underlying affective disorders. To assess the aetiology of affective disorders as well as the neuronal substrates underlying their regulation, we combine detailed ethological investigations with specific neurobiological techniques such as in vivo microdialysis and in situ hybridisation. As the investigation of novel pharmacological agents of potential future clinical use depends on animal models with face and predictive validity, it is another goal of the research group to develop causal and selective strategies to treat affective and anxiety disorders. During the past ten years at the Max Planck Institute of Psychiatry in Munich, we successively translated preclinical expertise into clinical approaches. These projects are performed in collaboration with research groups at the Max Planck Institute of Psychiatry in Munich and the Department of Pharmacology and Toxicology and Centre for Molecular Biosciences, University of Innsbruck.

Figure 1:  Response to antidepressant treatment

In patients with major depressive disorder treated for the first time, only about 30% will have a remission, which, since remission is associated with the best day-to-day functioning and prognosis, is the goal of treatment. In late-life affective disorders data are extremely sparse and the situation is considered to be even worse. Moreover, none of the potential strategies to accelerate speed of response have been clearly shown to be effective in these patients.

Future Projects

In close interdisciplinary collaboration, e.g., with Andreas Papassotiropoulos’ group, we will try to determine specific patterns of genetic polymorphisms predicting response to existing antidepressant/anxiolytic therapy and on the other hand we will try to identify novel yet unknown pathogenic mechanisms of both depression and anxiety disorders that could serve either as innovative drug targets and/or as markers for distinct subgroups. To this end, a carefully collected and phenotyped patient sample will be used to identify putative biomarkers and alleles predisposing to depression and anxiety disorders. This information will be integrated to provide insights into prevention, diagnostic, and therapeutic strategies of late-life depression, anxiety disorders and the putative development into cognitive impairment.

Anatomy research projects include software developments and application of the human thalamic and basal ganglia atlases for functional neurosurgery and imaging studies.

Techniques and Equipment

Basic Research: rodent microsurgery (in vivo microdialysis in freely moving rats and mice, implantation of chronic jugular vein catheters for continuous blood drawing), behavioural testing, in situ hybridization, immunohistochemistry.

Selected Publications

• Amador-Arjona, A., Delgado-Morales, R., Belda, X., Gagliano, H., Gallego, X., Keck, M.E., Armario, A., Dierssen, M. Susceptibility to stress in transgenic mice overexpressing TrkC, a model of panic disorder. J Psychiatr Res. Feb; 44(3): 157-67 (2010). Epub 2009 Aug 20.
• Hohoff, C., Mullings, E.L., Heatherley, S.V., Freitag, C.M., Neumann, L.C., Domschke, K., Krakowitzky, P., Rothermundt, M., Keck, M.E., Erhardt, A., Unschuld, P.G., Jacob, C., Fritze, J., Bandelow, B., Maier, W., Holsboer, F., Rogers, P.J., Deckert, J. Adenosine A(2A) receptor gene: Evidence for association of risk variants with panic disorder and anxious personality. J Psychiatr Res. Oct; 44(14): 930-7 (2010). Epub 2010 Mar 23.
• Toschi, N., Welt, T., Guerrisi, M., Keck, M.E.Transcranial magnetic stimulation in heterogeneous brain tissue: clinical impact on focality, reproducibility and true sham stimulation.J Psychiatr Res. Jan; 43(3): 255-64 (2009). Epub 2008 Jun 2.

Selected Lectures, Seminars, Colloquia

Clinical Psychiatry (see, e.g., www.forum-psychiatrie.ch)

Funding

German Federal Research Ministry “Competence Nets in Medicine” as PI within the project “Neurobiological mechanisms of antidepressant treatment”, Vontobel-Stiftung Zürich.