Effects of polygenic risk for major mental disorders and cross-disorder on cortical complexity

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Simon Schmitt - , University of Marburg, Justus Liebig University Giessen (Author)
  • Tina Meller - , University of Marburg, Justus Liebig University Giessen (Author)
  • Frederike Stein - , University of Marburg, Justus Liebig University Giessen (Author)
  • Katharina Brosch - , University of Marburg, Justus Liebig University Giessen (Author)
  • Kai Ringwald - , University of Marburg, Justus Liebig University Giessen (Author)
  • Julia Katharina Pfarr - , University of Marburg, Justus Liebig University Giessen (Author)
  • Clemens Bordin - , University of Marburg (Author)
  • Nina Peusch - , University of Marburg (Author)
  • Olaf Steinsträter - , University of Marburg (Author)
  • Dominik Grotegerd - , University of Münster (Author)
  • Katharina Dohm - , University of Münster (Author)
  • Susanne Meinert - , University of Münster (Author)
  • Katharina Förster - , University of Münster (Author)
  • Ronny Redlich - , University of Münster, Martin Luther University Halle-Wittenberg (Author)
  • Nils Opel - , University of Münster (Author)
  • Tim Hahn - , University of Münster (Author)
  • Andreas Jansen - , University of Marburg, Justus Liebig University Giessen (Author)
  • Andreas J. Forstner - , University of Marburg, University of Bonn, Jülich Research Centre (Author)
  • Fabian Streit - , Heidelberg University  (Author)
  • Stephanie H. Witt - , Heidelberg University  (Author)
  • Marcella Rietschel - , Heidelberg University  (Author)
  • Bertram Müller-Myhsok - , Ludwig Maximilian University of Munich, University of Liverpool (UOL), Max Planck Institute of Psychiatry (Author)
  • Markus M. Nöthen - , University of Bonn (Author)
  • Udo Dannlowski - , University of Münster (Author)
  • Axel Krug - , University of Marburg, Justus Liebig University Giessen, University of Bonn (Author)
  • Tilo Kircher - , University of Marburg, Justus Liebig University Giessen (Author)
  • Igor Nenadić - , University of Marburg, Justus Liebig University Giessen (Author)

Abstract

Background MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood. Methods We extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness. Results The PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing. Conclusions Changes in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome.

Details

Original languageEnglish
Pages (from-to)4127 - 4138
Number of pages12
JournalPsychological medicine
Volume52
Issue number16
Publication statusPublished - Dec 2022
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 33827729
WOS 000784424900001

Keywords

Sustainable Development Goals

Keywords

  • Bipolar disorder, brain development, cortical complexity, magnetic resonance imaging (MRI), major depressive disorder, polygenic risk, schizophrenia, surface-based morphometry, Brain development, Schizophrenia, Cortical complexity, Major depressive disorder, Surface-based morphometry, Polygenic risk