Sports Psychiatry

Head: Dr. med. Isabel Maurus

Description: “Mens sana in corpore sano" ("a healthy mind in a healthy body") is a Latin proverb that is still in line with current scientific findings. To date, there is ample evidence that regular physical activity has a positive effect on mental health and cognitive performance. These effects have also been shown for people with psychiatric illnesses such as schizophrenia. People with schizophrenia often suffer from persisting cognitive deficits and negative symptoms despite optimal pharmacological treatment. Additionally, individuals with schizophrenia consistently have higher morbidity and mortality than the general population, in part due to an increased risk for somatic comorbidities such as metabolic syndrome and cardiovascular diseases. In recent years, exercise has emerged as a possible new treatment option not only for the physical outcome of people with schizophrenia but also with regard to schizophrenia symptoms. However, many open questions remain about the neurobiological mechanisms responsible for the effects of aerobic endurance training. We currently conduct a multicentre, randomized, controlled clinical study that is the largest trial to date investigating the efficacy of aerobic endurance training in patients with schizophrenia. Using structural and functional magnetic resonance imaging, we explore the effects on global and regional cerebral volumes, white matter connectivity and the functional connectome. Moreover, we assess risk genes, genome-wide gene expression, epigenetics, and proteomics, including plasma levels of brain-derived neurotrophic factor and their influence on outcome parameters. Thereby, we want to enlarge our knowledge about the neuroplasticity processes of exercise to systematically establish a causal relationship between aerobic exercise, its neurobiological effects and outcome parameters.

Additionally, we will implement a discussion forum for exercise study partners, including clinician scientists, psychiatrists, psychologists, basic researchers, and representatives of patient, caregiver, and advocacy groups.

As a further project, we investigate motivational factors and barriers for healthy populations as well as people with mental illness to achieve a sufficient amount of physical activity to foster mental and physical health. In this context, we are particularly interested in the role of previous exercise history, personality-associated factors and reward experience after exercise.

In our outpatient clinic, we support professional athletes, who are usually exposed to extreme pressure, in promoting their mental health and take part in the scientific projects of the department of sports psychiatry of the DGPPN.

Main Areas of Interest:

- Neurobiological effects of exercise

- Somatic and clinical outcomes of exercise in people with mental disease

- Lifestyle interventions in severe mental illnesses

- Barriers and motivating factors towards regular physical activity

- Prevention, diagnosis and treatment of mental disease in professional athletes

Current projects:

BrainTrain study (Insights into hippocampal neuroplasticity in schizophrenia by investigating molecular pathways during physical endurance training)

The exercise study BrainTrain, funded by the German Research Foundation e.V., is a two-arm, randomized, parallel-group clinical trial with patients with clinically stable schizophrenia (SZ), conducted at the Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich. The study aims to identify the biological mechanisms explaining the improvement of clinical symptoms in SZ through physical activity. Furthermore, the influence on the genetic risk profile will be explored. The intervention group will perform aerobic endurance training on bicycle ergometers for 40-45 minutes/session (depending on the intervention week) three times a week for a duration of 13 weeks, while the control group will perform balance and strengthening training for the same duration. The primary endpoint is the change in hippocampal volume, while secondary endpoints include psychopathology, cognition, daily functioning, cardiovascular risk factors, and exploratory biological measures of the underlying mechanisms of exercise. A total of 156 patients will be included and randomized. In addition, data from 65 subjects of the completed ESPRIT study will be integrated in the analysis. It is assumed that aerobic endurance training has a positive effect on the mental and physical health of patients’ disease outcome. The results of the study will provide a basis for recommending exercise interventions as adjunctive therapy in patients with schizophrenia. The study is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier: NCT05956327) and in the German Register for Clinical Trials (DRKS ID: DRKS00032187).

OligoTreat study (Combining Clemastine and Aerobic Exercise to Treat Cognitive Dysfunction in Schizophrenia by Targeting Myelin Plasticity)

Impaired connectivity is related to synaptic (microconnectivity) and myelin (macroconnectivity) plasticity. With design-based stereology, a decreased number of oligodendrocytes (OLs) in the CA4 hippocampal subregion as the basis for disturbed myelination and impaired cognition, but also a decrease in the prefrontal cortex were observed. Animal studies demonstrated that clemastine enhances remyelination by increasing the differentiation of oligodendrocyte precursor cells (OPCs) and showed that aerobic exercise increases the rate of remyelination and proliferation of OPCs; this clinically meaningful effect of aerobic exercise is stronger in combination with clemastine. Furthermore, aerobic exercise improves everyday functioning, measured by the Global Assessment of Functioning (GAF) scale, and cognitive dysfunction in SZ and increases hippocampal volume, especially the volume in the hippocampal CA4 subregion. This regional volume change correlates negatively with global and cell-specific polygenic risk scores (PRSs), indicating that OPCs are involved in the genetic risk mechanisms and disturbed plasticity underlying SZ. In patients with multiple sclerosis, 90 days' administration of clemastine fumarate 10.72 mg/day, corresponding to clemastine 8 mg/day, significantly decreased the P100 latency delay of visual evoked potentials (VEPs) as a sign of myelin repair. In a bicentric, randomized, double-blind, controlled phase IIb clinical trial with a 2-arm parallel group design in patients with SZ, we will compare the effects of aerobic exercise training plus clemastine vs. aerobic exercise training plus placebo over a period of 3 months on 1) everyday functioning and 2) working memory as primary outcomes. The study is registered in the German Register for Clinical Trials (DRKS ID: DRKS00032316).

Publications:

1. Falkai, P., Rossner, M. J., Raabe, F. J., Wagner, E., Keeser, D., Maurus, I., Roell, L., Chang, E., Seitz-Holland, J., Schulze, T. G., & Schmitt, A. (2023). Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis. Schizophrenia Bulletin. doi: 10.1093/schbul/sbad065

2. Roell, L., Fischer, T., et al. (2023). Effects of Aerobic Exercise on Hippocampal Formation Volume in People with Schizophrenia – A Systematic Review and Meta-Analysis with Original Data from a Randomized-Controlled Trial. https://doi.org/10.31219/osf.io/y2phs

3. Roell, L., Keeser, D., Papazov, B., Lembeck, M., Papazova, I., Greska, D., Muenz, S., Schneider-Axmann, T., Sykorova, E. B., Thieme, C. E., et al. (2023). Effects of Exercise on Structural and Functional Brain Patterns in Schizophrenia - Data From a Multicenter Randomized-Controlled Study. Schizophrenia Bulletin. doi: 10.1093/schbul/sbad113

4. Maurus, I., Roell, L., Lembeck, M., Papazova, I., Greska, D., Muenz, S., Wagner, E., Campana, M., Schwaiger, R., Schneider-Axmann, T., et al. (2023). Exercise as an Add-on Treatment in Individuals with Schizophrenia: Results from a Large Multicenter Randomized Controlled Trial. Psychiatry Research. doi: 10.1016/j.psychres.2023.115480

5. Roell, L., Maurus, I., Keeser, D., Karali, T., Papazov, B., Hasan, A., Schmitt, A., Papazova, I., Lembeck, M., Hirjak, D., et al. (2022). Association Between Aerobic Fitness and the Functional Connectome in Patients with Schizophrenia. European Archives of Psychiatry and Clinical Neuroscience, 2022. doi: 10.1007/s00406-022-01411-x

6. Maurus, I., Roell, L., Keeser, D., Karali, T., Papazov, B., Hasan, A., Schmitt, A., Papazova, I., Lembeck, M., Hirjak, D., Thieme, C. E., et al. (2022). Associations Between Aerobic Fitness, Negative Symptoms, Cognitive Deficits and Brain Structure in Schizophrenia - A Cross-Sectional Study. Schizophrenia, 2022. doi: 10.1038/s41537-022-00269-1

7. Maurus, I., Hasan, A., Schmitt, A., Roeh, A., Keeser, D., Malchow, B., Schneider-Axmann, T., Hellmich, M., Schmied, S., Lembeck, M., et al. (2021). Aerobic Endurance Training to Improve Cognition and Enhance Recovery in Schizophrenia: Design and Methodology of a Multicenter Randomized Controlled Trial. European Archives of Psychiatry and Clinical Neuroscience, 2021. doi: 10.1007/s00406-020-01175-2

8. Falkai, P., Schmitt, A., Rosenbeiger, C. P., Maurus, I., Hattenkofer, L., Hasan, A., Malchow, B., Heim-Ohmayer, P., Halle, M., & Heitkamp, M. (2021). Aerobic Exercise in Severe Mental Illness: Requirements from the Perspective of Sports Medicine. European Archives of Psychiatry and Clinical Neuroscience, 2021. doi: 10.1007/s00406-021-01360-x

1. Papiol S., Schmitt A., Maurus I, Rossner M., Schulze T., Falkai P. (2021). Association Between Physical Activity and Schizophrenia: Results of a 2-Sample Mendelian Randomization Analysis. JAMA Psychiatry. 78(4): p. 441-444.

2. Falkai P, Maurus I, Schmitt A, Malchow B, Schneider-Axmann T, Röll L, Papiol S, Wobrock T, Hasan A, and Keeser D (2021) Improvement in daily functioning after aerobic exercise training in schizophrenia is sustained after exercise cessation. Eur Arch Psychiatry Clin Neurosci 271: 1201-1203. 10.1007/s00406-021-01282-8

3. Maurus I, Hasan A, Roeh A, Keeser D, Malchow B, Keller-Varady K, Papazova I, Hirjak D, Topor C, Walter H, Mohnke S, Vogel B, Wölwer W, Schneider F, Henkel K, Meyer-Lindenberg A, Falkai P (2020). Endurance training for the improvement of cognition and enhancement of recovery in schizophrenia: study design and methodology of a multicenter randomized, controlled trial. PRJ-2019-0285

4. Takahashi S, Keeser D, Rauchmann B-S, Schneider-Axmann T, Keller-Varady K, Maurus I, Dechent P, Wobrock T, Hasan A, and Schmitt A (2020) Effect of aerobic exercise on cortical thickness in patients with schizophrenia–a dataset. Data in Brief: 105517.

5. Maurus I, Hasan A, Röh A, Takahashi S, Rauchmann B, Keeser D, Schmitt A, Falkai, P. (2019): Neurobiological effects of aerobic exercise, with a focus on patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci, 269(5): 1-17.

6. Rauchmann BS, Ghaseminejad F, Keeser D, Keller-Varady K, Schneider-Axmann T, Takahashi S, Karali T, Helms G, Dechent P, Maurus I, Hasan A, Wobrock T, Ertl-Wagner B, Schmitt A, Malchow B, and Falkai P (2019) The impact of endurance training and table soccer on brain metabolites in schizophrenia. Brain Imaging Behav. 10.1007/s11682-019-00198-1

7. Maurus I, Röh A, Falkai P, Malchow B, Schmitt A, Hasan A. (2019): Nonpharmacological treatment of dyscognition in schizophrenia: effects of aerobic exercise. Dialogues In Clinical Neuroscience, 21(3): 261-269.

8. Maurus I, Mantel C, Keller-Varady K, Schmitt A, Lembeck M, Röh A, Papazova I, Falkai P, Schneider-Axmann T, Malchow B, Hasan A. (2019): Resistance training in patients with schizophrenia: Concept and proof of principle trial. J Psychiatr Res., 120(1): 72-82.

9. Takahashi S, Keeser D, Rauchmann S, Schneider-Axmann T, Keller-Varady K, Maurus I, Dechent P, Wobrock T, Hasan A, Schmitt A, Ertl-Wagner B, Malchow B, Falkai, P (2019): Effect of aerobic exercise combined with cognitive remediation on cortical thickness and prediction of social adaptation in patients with schizophrenia. Schizophr Res

10. Roeh A, Kirchner S, Malchow B, Maurus I, Schmitt A, Falkai P, Hasan A (2019). Depression in somatic disorders: is there a beneficial effect of exercise? Front Psychiatry, 10, 141. doi:10.3389/fpsyt.2019.00141.

11. Schmitt A, Maurus I, Rossner MJ, Roeh A, Lembeck M, von Wilmsdorff M, Takahashi S, Rauchmann B, Kesser D, Hasan A, Malchow B, Falkai P (2018): Effects of aerobic exercise on metabolic syndrome, cardiorespiratory fitness, and symptoms in schizophrenia include decreased mortality. Front Psychiatry, 9, 690. doi:10.3389/fpsyt.2018.00690

12. Schmitt A, Malchow B, Lembeck M, Maurus I, Roeh A, Papiol S,Hasan A, Falkai P. (2018). Bedeutung von Ausdauersport für die Verbesserung von Kognition und Remission bei post-akuter Schizophrenie. Nervenheilkunde, 37(05): 324-329.

13. Keller-Varady K, Varady PA, Roeh A, Schmitt A, Falkai P, Hasan A, and Malchow B (2018) A systematic review of trials investigating strength training in schizophrenia spectrum disorders. Schizophrenia research 192: 64-68.

14. Falkai P, Malchow B, and Schmitt A (2017) Aerobic exercise and its effects on cognition in schizophrenia. Curr Opin Psychiatry 30: 171-175. 10.1097/yco.0000000000000326

15. Malchow B, Keeser D, Keller K, Hasan A, Rauchmann BS, Kimura H, Schneider-Axmann T, Dechent P, Gruber O, Ertl-Wagner B, Honer WG, Hillmer-Vogel U, Schmitt A, Wobrock T, Niklas A, and Falkai P (2016) Effects of endurance training on brain structures in chronic schizophrenia patients and healthy controls. Schizophr Res 173: 182-191. 10.1016/j.schres.2015.01.005

16. Keller-Varady K, Hasan A, Schneider-Axmann T, Hillmer-Vogel U, Adomssent B, Wobrock T, Schmitt A, Niklas A, Falkai P, and Malchow B (2016) Endurance training in patients with schizophrenia and healthy controls: differences and similarities. Eur Arch Psychiatry Clin Neurosci 266: 461-73. 10.1007/s00406-015-0651-8

17. Malchow B, Keller K, Hasan A, Dorfler S, Schneider-Axmann T, Hillmer-Vogel U, Honer WG, Schulze TG, Niklas A, Wobrock T, Schmitt A, and Falkai P (2015) Effects of Endurance Training Combined With Cognitive Remediation on Everyday Functioning, Symptoms, and Cognition in Multiepisode Schizophrenia Patients. Schizophr Bull 41: 847-58. 10.1093/schbul/sbv020

Our Team:

- Prof. Dr. med. Peter Falkai

- Prof. Dr. med. Andrea Schmitt

- Dr. med. Isabel Maurus

- Dr. med. Joanna Moussiopoulou

- Dr. rer. biol. hum. Lukas Röll

- Dr. med Vladislav Yakimov

- Lena Deller, M.Sc and PhD candidate

- Mona Hussain, M.Sc and PhD candidate

- Jasmin Jannan, doctoral student

- Julia Segerer, M.Sc.

- Johanna Späth, M.Sc and PhD candidate

- Annemarie Weibel, doctoral student

- Deniz Yilmaz, M.Sc and PhD candidate

- Miriam Zuliani, doctoral student

Collaborations:

- Klinik für Psychiatrie, Psychotherapie und Psychosomatik der Universität Augsburg

- ZI Mannheim

- RTWH Aachen

- Universitätsklinikum Düsseldorf

- Charité Berlin

- Präventive Sportmedizin und Sportkardiologie, TU München

- DGSPP

- DGPPN Referat Sportpsychiatrie