Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2017 Jun 27;7(6):e1159.
doi: 10.1038/tp.2017.131.

Polygenic risk has an impact on the structural plasticity of hippocampal subfields during aerobic exercise combined with cognitive remediation in multi-episode schizophrenia

S Papiol  1   2 , D Popovic  1 , D Keeser  1   3 , A Hasan  1 , T Schneider-Axmann  1 , F Degenhardt  4 , M J Rossner  1 , H Bickeböller  5 , A Schmitt  1   6 , P Falkai  1 , B Malchow  1
Affiliations
Clinical Trial

Polygenic risk has an impact on the structural plasticity of hippocampal subfields during aerobic exercise combined with cognitive remediation in multi-episode schizophrenia

S Papiol et al. Transl Psychiatry. .

Abstract

Preliminary studies suggest that, besides improving cognition, aerobic exercise might increase hippocampal volume in schizophrenia patients; however, results are not consistent. Individual mechanisms of volume changes are unknown but might be connected to the load of risk genes. Genome-wide association studies have uncovered the polygenic architecture of schizophrenia. The secondary analysis presented here aimed to determine the modulatory role of schizophrenia polygenic risk scores (PRSs) on volume changes in the total hippocampus and cornu ammonis (CA) 1, CA2/3, CA4/dentate gyrus (DG) and subiculum over time. We studied 20 multi-episode schizophrenia patients and 23 healthy controls who performed aerobic exercise (endurance training) combined with cognitive remediation for 3 months and 21 multi-episode schizophrenia patients allocated to a control intervention (table soccer) combined with cognitive remediation. Magnetic resonance imaging-based assessments were performed at baseline and after 3 months with FreeSurfer. No effects of PRSs were found on total hippocampal volume change. Subfield analyses showed that the volume changes between baseline and 3 months in the left CA4/DG were significantly influenced by PRSs in schizophrenia patients performing aerobic exercise. A larger genetic risk burden was associated with a less pronounced volume increase or a decrease in volume over the course of the exercise intervention. Results of exploratory enrichment analyses reinforced the notion of genetic risk factors modulating biological processes tightly related to synaptic ion channel activity, calcium signaling, glutamate signaling and regulation of cell morphogenesis. We hypothesize that a high polygenic risk may negatively influence neuroplasticity in CA4/DG during aerobic exercise in schizophrenia.

PubMed Disclaimer

Conflict of interest statement

A Hasan has been invited to scientific meetings by Lundbeck, Janssen-Cilag and Pfizer, received a paid speakership from Desitin, Otsuka and Lundbeck, and was a member of a Roche advisory board. P Falkai has been an honorary speaker for AstraZeneca, Bristol Myers Squibb, Eli Lilly, Essex, GE Healthcare, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Servier and Takeda, and during the past 5 years, but not presently, has been a member of the advisory boards of Janssen-Cilag, AstraZeneca, Eli Lilly and Lundbeck. A Schmitt has been an honorary speaker for TAD Pharma and Roche, and a member of advisory boards for Roche. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scatterplot showing the relationship between the optimal schizophrenia polygenic risk score (PRS; x axis, standardized) and the change from baseline (V1) in the volume of the hippocampal subfields CA1 (left panel), CA2/3 (middle panel) and CA4/dentate gyrus (right panel) after 3 months of aerobic exercise (V3) (y axis, corrected residuals). Positive values in the y axis indicate a gain in volume after 3 months; positive values in the x axis, a higher genetic risk burden. Regression line and 95% confidence intervals are also shown.
Figure 2
Figure 2
Results of the formal enrichment analyses summarizing the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) or Reactome pathways enriched in this study with a Bonferroni-corrected adjusted P-value<0.05. Red line: nominal significance threshold (0.05) of corrected P-values.
See this image and copyright information in PMC

References

    1. Adriano F, Caltagirone C, Spalletta G. Hippocampal volume reduction in first-episode and chronic schizophrenia: a review and meta-analysis. Neurosci Rev J 2012; 18: 180–200. - PubMed
    1. van Erp TGM, Hibar DP, Rasmussen JM, Glahn DC, Pearlson GD, Andreassen OA et al. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Mol Psychiatry 2016; 21: 547–553. - PMC - PubMed
    1. Geisler D, Walton E, Naylor M, Roessner V, Lim KO, Charles Schulz S et al. Brain structure and function correlates of cognitive subtypes in schizophrenia. Psychiatry Res 2015; 234: 74–83. - PMC - PubMed
    1. Hasan A, Wobrock T, Falkai P, Schneider-Axmann T, Guse B, Backens M et al. Hippocampal integrity and neurocognition in first-episode schizophrenia: a multidimensional study. World J Biol Psychiatry 2014; 15: 188–199. - PubMed
    1. Mitelman SA, Brickman AM, Shihabuddin L, Newmark RE, Hazlett EA, Haznedar MM et al. A comprehensive assessment of gray and white matter volumes and their relationship to outcome and severity in schizophrenia. NeuroImage 2007; 37: 449–462. - PMC - PubMed

Publication types