Association between aerobic fitness and the functional connectome in patients with schizophrenia

• Published in: European archives of psychiatry and clinical neuroscience 2022-10, Vol.272 (7), p.1253-1272
• Main Authors: Roell, Lukas, Maurus, Isabel, Keeser, Daniel, Karali, Temmuz, Papazov, Boris, Hasan, Alkomiet, Schmitt, Andrea, Papazova, Irina, Lembeck, Moritz, Hirjak, Dusan, Sykorova, Eliska, Thieme, Cristina E., Muenz, Susanne, Seitz, Valentina, Greska, David, Campana, Mattia, Wagner, Elias, Loehrs, Lisa, Stoecklein, Sophia, Ertl-Wagner, Birgit, Poemsl, Johannes, Roeh, Astrid, Malchow, Berend, Keller-Varady, Katriona, Meyer-Lindenberg, Andreas, Falkai, Peter
• Format: Article
• Language: English
• Subjects: Bayesian analysis; Brain; Brain mapping; Cardiorespiratory fitness; Care and treatment; Cerebellum; Clinical trials; Cognition; Cognition & reasoning; Cognitive ability; Exercise; Functional magnetic resonance imaging; Health aspects; Mediation; Medicine; Medicine & Public Health; Mental disorders; Neural networks; Neurosciences; Original Paper; Patients; Physical fitness; Psychiatry; Schizophrenia; Seeds
• ISSN: 0940-1334; 1433-8491
• DOI: 10.1007/s00406-022-01411-x

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).