Lukas Roell1,2, Isabel Maurus3, Daniel Keeser3,4,5, Temmuz Karali3,4,5, Boris Papazov4, Alkomiet Hasan6, Andrea Schmitt3,7, Irina Papazova6, Moritz Lembeck3, Dusan Hirjak8, Eliska Sykorova8, Cristina E Thieme8, Susanne Muenz3, Valentina Seitz3, David Greska3, Mattia Campana3, Elias Wagner3, Lisa Loehrs3, Sophia Stoecklein4, Birgit Ertl-Wagner4,9, Johannes Poemsl10, Astrid Roeh6, Berend Malchow11, Katriona Keller-Varady12, Andreas Meyer-Lindenberg8, Peter Falkai3. 1. Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Nussbaumstrasse 7, 80336, Munich, Germany. Lukas.Roell@med.uni-muenchen.de. 2. NeuroImaging Core Unit Munich (NICUM), University Hospital LMU, Munich, Germany. Lukas.Roell@med.uni-muenchen.de. 3. Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Nussbaumstrasse 7, 80336, Munich, Germany. 4. Department of Radiology, University Hospital, LMU Munich, Munich, Germany. 5. NeuroImaging Core Unit Munich (NICUM), University Hospital LMU, Munich, Germany. 6. Department of Psychiatry and Psychosomatics of the University Augsburg, Bezirkskrankenhaus Augsburg, University of Augsburg, Augsburg, Germany. 7. Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of Sao Paulo, São Paulo, Brazil. 8. Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. 9. Division of Neuroradiology, Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Canada. 10. Department of Psychiatry and Psychotherapy, Medical Faculty, Technical University of Munich, University Hospital 'Klinikum Rechts Der Isar', Munich, Germany. 11. Department of Psychiatry and Psychotherapy, University Hospital Göttingen, Göttingen, Germany. 12. Hannover Medical School, Institute of Sports Medicine, Hannover, Germany.
Abstract
BACKGROUND: Schizophrenia is accompanied by widespread alterations in static functional connectivity associated with symptom severity and cognitive deficits. Improvements in aerobic fitness have been demonstrated to ameliorate symptomatology and cognition in people with schizophrenia, but the intermediary role of macroscale connectivity patterns remains unknown. OBJECTIVE: Therefore, we aim to explore the relation between aerobic fitness and the functional connectome in individuals with schizophrenia. Further, we investigate clinical and cognitive relevance of the identified fitness-connectivity links. METHODS: Patients diagnosed with schizophrenia were included in this cross-sectional resting-state fMRI analysis. Multilevel Bayesian partial correlations between aerobic fitness and functional connections across the whole brain as well as between static functional connectivity patterns and clinical and cognitive outcome were performed. Preliminary causal inferences were enabled based on mediation analyses. RESULTS: Static functional connectivity between the subcortical nuclei and the cerebellum as well as between temporal seeds mediated the attenuating relation between aerobic fitness and total symptom severity. Functional connections between cerebellar seeds affected the positive link between aerobic fitness and global cognition, while the functional interplay between central and limbic seeds drove the beneficial association between aerobic fitness and emotion recognition. CONCLUSION: The current study provides first insights into the interactions between aerobic fitness, the functional connectome and clinical and cognitive outcome in people with schizophrenia, but causal interpretations are preliminary. Further interventional aerobic exercise studies are needed to replicate the current findings and to enable conclusive causal inferences. TRIAL REGISTRATION: The study which the manuscript is based on is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).
BACKGROUND: Schizophrenia is accompanied by widespread alterations in static functional connectivity associated with symptom severity and cognitive deficits. Improvements in aerobic fitness have been demonstrated to ameliorate symptomatology and cognition in people with schizophrenia, but the intermediary role of macroscale connectivity patterns remains unknown. OBJECTIVE: Therefore, we aim to explore the relation between aerobic fitness and the functional connectome in individuals with schizophrenia. Further, we investigate clinical and cognitive relevance of the identified fitness-connectivity links. METHODS: Patients diagnosed with schizophrenia were included in this cross-sectional resting-state fMRI analysis. Multilevel Bayesian partial correlations between aerobic fitness and functional connections across the whole brain as well as between static functional connectivity patterns and clinical and cognitive outcome were performed. Preliminary causal inferences were enabled based on mediation analyses. RESULTS: Static functional connectivity between the subcortical nuclei and the cerebellum as well as between temporal seeds mediated the attenuating relation between aerobic fitness and total symptom severity. Functional connections between cerebellar seeds affected the positive link between aerobic fitness and global cognition, while the functional interplay between central and limbic seeds drove the beneficial association between aerobic fitness and emotion recognition. CONCLUSION: The current study provides first insights into the interactions between aerobic fitness, the functional connectome and clinical and cognitive outcome in people with schizophrenia, but causal interpretations are preliminary. Further interventional aerobic exercise studies are needed to replicate the current findings and to enable conclusive causal inferences. TRIAL REGISTRATION: The study which the manuscript is based on is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).
Authors: Joseph Ventura; Gerhard S Hellemann; April D Thames; Vanessa Koellner; Keith H Nuechterlein Journal: Schizophr Res Date: 2009-07-22 Impact factor: 4.939
Authors: Michael Wibral; Joseph T Lizier; Sebastian Vögler; Viola Priesemann; Ralf Galuske Journal: Front Neuroinform Date: 2014-01-28 Impact factor: 4.081