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

Simon Schmitt; Tina Meller; Frederike Stein; Katharina Brosch; Kai Ringwald; Julia-Katharina Pfarr; Clemens Bordin; Nina Peusch; Olaf Steinsträter; Dominik Grotegerd; Katharina Dohm; Susanne Meinert; Katharina Förster; Ronny Redlich; Nils Opel; Tim Hahn; Andreas Jansen; Andreas J Forstner; Fabian Streit; Stephanie H Witt; Marcella Rietschel; Bertram Müller-Myhsok; Markus M Nöthen; Udo Dannlowski; Axel Krug; Tilo Kircher; Igor Nenadić

doi:10.1017/S0033291721001082

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

Psychol Med. 2021 Apr 8;52(16):1-12. doi: 10.1017/S0033291721001082. Online ahead of print.

Authors

Simon Schmitt^{1

2

3}, Tina Meller^{1

2}, Frederike Stein^{1

2}, Katharina Brosch^{1

2

3}, Kai Ringwald^{1

2}, Julia-Katharina Pfarr^{1

2}, Clemens Bordin¹, Nina Peusch¹, Olaf Steinsträter¹, Dominik Grotegerd⁴, Katharina Dohm⁴, Susanne Meinert⁴, Katharina Förster⁴, Ronny Redlich^{4

5}, Nils Opel⁴, Tim Hahn⁴, Andreas Jansen^{1

2

6}, Andreas J Forstner^{7

8

9}, Fabian Streit¹⁰, Stephanie H Witt¹⁰, Marcella Rietschel¹⁰, Bertram Müller-Myhsok^{11

12

13}, Markus M Nöthen⁸, Udo Dannlowski⁴, Axel Krug^{1

2

14}, Tilo Kircher^{1

2

3}, Igor Nenadić^{1

2

3}

Affiliations

¹ Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg, Rudolf-Bultmann-Str. 8, 35039Marburg, Germany.
² Center for Mind, Brain and Behavior (CMBB), Philipps-Universität Marburg and Justus Liebig Universität Giessen, Hans-Meerwein-Str. 6, 35032Marburg, Germany.
³ Marburg University Hospital - UKGM, Rudolf-Bultmann-Str. 8, 35039Marburg, Germany.
⁴ Department of Psychiatry, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, Building A9, 48149Münster, Germany.
⁵ Department of Psychology, University of Halle, Halle, Germany.
⁶ Faculty of Medicine, Core-Facility BrainImaging, Philipps-Universität Marburg, Rudolf-Bultmann-Str. 8, 35039, Germany.
⁷ Centre for Human Genetics, Philipps-Universität Marburg, Baldingerstr., 35033Marburg, Germany.
⁸ Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Venusberg-Campus 1, 53127Bonn, Germany.
⁹ Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Wilhelm-Johnen-Straße, 52428Jülich, Germany.
¹⁰ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159Mannheim, Germany.
¹¹ Munich Cluster for Systems Neurology (SyNergy), Feodor-Lynen-Str. 17, 81377Munich, Germany.
¹² Institute of Translational Medicine, University of Liverpool, Crown Street, LiverpoolL69 3BX, UK.
¹³ Max-Planck-Institute of Psychiatry, Kraepelinstr. 2-10, 80804Munich, Germany.
¹⁴ Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.

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.

Keywords: Bipolar disorder; brain development; cortical complexity; magnetic resonance imaging (MRI); major depressive disorder; polygenic risk; schizophrenia; surface-based morphometry.