Traumatic Stress and Neurodegeneration
Research group of the Department of Psychiatry and Psychotherapy
Posttraumatic Stress Disorder (PTSD) is an incapacitating mental illness that can develop in the aftermath of traumatic experiences such as (sexual) violence, serious accidents, natural disasters or emotional neglect in childhood. PTSD often leads to social isolation and incapacity to work. PTSD core symptoms comprise the pathognomonic aversive recalls of trauma reminders (flashbacks), avoidance of trauma-associated cues, nervous hyperexcitability and emotional numbness. Exposure-based psychotherapy has proven to be effective in PTSD treatment, however, PTSD treatment sites are scarce and it usually takes months until the first beneficial effects of PTSD psychotherapy emerge. SSRI-type antidepressants are also effective in treatment of PTSD patients, but, however, not in all of them, and, moreover, they do not lead to full remission in a substantial amount of cases.
Thus, the optimization of treatment options for PTSD is urgently needed. The identification of molecular target structures for novel drugs (so-called drug targets) is therefore one of the main goals of PTSD research, another is the identification of biomarkers that could aid in the selection of the most appropriate therapeutic method, in differential diagnosis and, finally, inprevention of this serious disease.
In comparison to to these two topics, on which Ulrike Schmidt has worked on with her former research group at the MPI for Psychiatry in Munich till 2017, the molecular basis of the long-term consequences of PTSD, which comprise inter alia alterations in the cardiovascular and metabolic systems (Raue et al., 2019) as well as premature or pathologically accelerated neurodegeneration (Agís-Balboa et al., 2017), has so far been addressed only by a few studies.
Main goals
For this reason, the main goal of our research group is to the identify the so far only fragmentary explored molecular mechanisms of stress modulation of neurodegeneration and neurodegenerative disorders by combining clinical with molecular biological and biochemical analysis research methods.
Selection of current research projects
UMG-UKB-PTSD cohort project
Recruitment of a longitudinal PTSD cohort (collaboration cohort of the two research groups and Trauma Outpatient Clinics (Universities of Göttingen (UMG) and of Bonn (UKB)) of Ulrike Schmidt at the Clinic for Psychiatry and Psychotherapy of the Universities of Göttingen and Bonn) – analyses at the UMG will focus on neurodegeneration-associated markers.
Long-term metabolic consequences of PTSD and interaction with neurodegenerative processes
(project of Stefan Raue)
This project started with a narrative review in which we have recently summarized the previous literature on this topic (Raue et al., 2019). We aim to assess the consequences of stress (and its maximal form, trauma) as well as the influence of stress on the metabolic system at the molecular level.
Trier Social Stress Test (TSST) PTSD project
Using the TSST, the former Munich research group of Ulrike Schmidt has identified stress reactivity endophenotypes of PTSD in TSST experiments (Zaba et al., 2015) which are possibly related to the pathogenesis and/or maintenance of certain symptoms of the PTSD syndrome. Together with the research group of Prof. Dirk Wedekind we are currently investigating whether physical activity (which is known to modulate neuroplastic processes) may affect the stress reactivity of PTSD patients. In a second step we will analyze the relationship between stress reactivity and bioamrkers for neurodegeneration.
References
Raue, S., Wedekind, D., Wiltfang, J., Schmidt, U., 2019. The Role of Proopiomelanocortin and α-Melanocyte-Stimulating Hormone in the Metabolic Syndrome in Psychiatric Disorders: A Narrative Mini-Review. Front. Psychiatry 10. https://doi.org/10.3389/fpsyt.2019.00834
Zaba, M., Kirmeier, T., Ionescu, I.A., Wollweber, B., Buell, D.R., Gall-Kleebach, D.J., Schubert, C.F., Novak, B., Huber, C., Köhler, K., Holsboer, F., Pütz, B., Müller-Myhsok, B., Höhne, N., Uhr, M., Ising, M., Herrmann, L., Schmidt, U., 2015. Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients. Psychoneuroendocrinology 55, 102–115. https://doi.org/10.1016/j.psyneuen.2015.02.005
Collaborations
Internal:
- Prof. Dr. D. Wedekind (TSST study)
- Priv.-Doz. Dr. D. Zilles (ECT biomarker project)
External (Highthroughput Array Analyses):
- Klinik für Psychiatrie und Psychotherapie der Universität Bonn
- Psychotraumazentrum des Bundeswehrkrankenhauses (German Armed Forces) n Berlin
- Psychiatry Division of Maastricht University, The Netherlands