The impact of endurance training and table soccer on brain metabolites in schizophrenia
Higher glutamate and glutamine (together: Glx) and lower N-acetyl-aspartate (NAA) levels were reported in schizophrenia. Endurance training normalizes NAA in the hippocampus, but its effects on other metabolites in the brain and the relationship of metabolites to clinical symptoms remain unknown. For 12 weeks, 20 schizophrenia inpatients (14 men, 6 women) and 23 healthy controls (16 men, 7 women) performed endurance training and a control group of 21 schizophrenia inpatients (15 men, 6 women) played table soccer. A computer-assisted cognitive performance training program was introduced after 6 weeks. We assessed cognitive performance, psychopathological symptoms, and everyday functioning at baseline and after 6 and 12 weeks and performed single voxel magnetic resonance spectroscopy of the hippocampus, left dorsolateral prefrontal cortex (DLPFC), and thalamus. We quantified NAA, Glx, total creatine (tCr), calculated NAA/tCr and Glx/tCr and correlated these ratios with physical fitness, clinical and neurocognitive scores, and everyday functioning. At baseline, in both schizophrenia groups NAA/tCr was lower in the left DLPFC and left hippocampus and Glx/tCr was lower in the hippocampus than in the healthy controls. After 6 weeks, NAA/tCr increased in the left DLPFC in both schizophrenia groups. Brain metabolites did not change significantly in the hippocampus or thalamus, but the correlation between NAA/tCr and Glx/tCr normalized in the left DLPFC. Global Assessment of Functioning improvements correlated with NAA/tCr changes in the left DLPFC. In our study, endurance training and table soccer induced normalization of brain metabolite ratios in the brain circuitry associated with neuronal and synaptic elements, including metabolites of the glutamatergic system.
KeywordsSchizophrenia MRS Aerobic exercise NAA Glx Clinical symptoms
Study concept and design: Falkai, Malchow, Rauchmann. Analysis and interpretation of data: Rauchmann, Ghaseminejad, Keller-Varady, Keeser, Karali, Schneider-Axmann. Drafting of the manuscript: Rauchmann, Ghaseminejad. Critical revision of the manuscript for important intellectual content: Rauchmann, Schmitt, Helms, Keeser, Hasan, Helms, Dechent, Takahashi, Maurus. Statistical analysis: Rauchmann, Schneider-Axmann. Administrative, technical, and material support: Falkai, Malchow, Ertl-Wagner. Study supervision: Falkai, Schmitt, Malchow. All authors contributed to and approved the final manuscript.
This research was funded by the grants Klinische Forschergruppe (KFO) 241 and PsyCourse (FA241/16–1) from the Deutsche Forschungsgemeinschaft (DFG). Further funding was received from the German Federal Ministry of Education and Research (BMBF) through the research network on psychiatric diseases ESPRIT (grant number 01EE1407E). The funding sources were not involved in study design, collection, analysis and interpretation of data, or writing of the report or in the decision to submit the article for publication.
Compliance with ethical standards
Conflict of interest
S. Takahashi, D. Keeser, F. Ghaseminejad, B.-S. Rauchmann, G. Helms, T. Karali, T. Schneider-Axmann, I. Maurus, K Keller-Varady, P. Dechent, B. Ertl-Wagner, and B. Malchow report no conflicts of interest. T. Wobrock was a member of the Advisory Board of Janssen Cilag and Otsuka/Lundbeck and has accepted paid speaking engagements for Alpine Biomed, AstraZeneca, Bristol Myers Squibb, Eli Lilly, I3G, Glaxo-Smith-Kline, Janssen Cilag, Novartis, Lundbeck, Otsuka, Roche, Sanofi-Aventis and Pfizer. He has received research grants from AstraZeneca, Cerbomed, I3G, and AOK (health insurance company). In addition, he received research support from The German Research Funding Organisation (DFG) and the Federal Ministry of Education and Research (BMBF). A. Hasan received honoraria from Desitin, Otsuka, Janssen-Cilag, and Lundbeck and was a member of the advisory boards of Roche, Janssen-Cilag, and Lundbeck. P. Falkai has been an honorary speaker for AstraZeneca, Bristol Myers Squibb, Lilly, Essex, GE Healthcare, GlaxoSmithKline, Janssen Cilag, Lundbeck, Otsuka, Pfizer, Servier, and Takeda and has been a member of the advisory boards of Janssen-Cilag, AstraZeneca, Lilly, and Lundbeck. A. Schmitt was an honorary speaker for TAD Pharma and Roche and a member of the Roche advisory board.
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
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