Polygenic risk for depression and the neural correlates of working memory in healthy subjects

Dilara Yüksel; Bruno Dietsche; Andreas J Forstner; Stephanie H Witt; Robert Maier; Marcella Rietschel; Carsten Konrad; Markus M Nöthen; Udo Dannlowski; Bernhard T Baune; Tilo Kircher; Axel Krug

doi:10.1016/j.pnpbp.2017.06.010

Polygenic risk for depression and the neural correlates of working memory in healthy subjects

Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):67-76. doi: 10.1016/j.pnpbp.2017.06.010. Epub 2017 Jun 15.

Authors

Affiliations

¹ Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany. Electronic address: dilara.yueksel@med.uni-marburg.de.
² Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
³ Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany; Institute of Human Genetics, University of Bonn, Bonn, Germany; Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland; Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
⁴ Discipline Department of Genetic Epidemiology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
⁵ Discipline Queensland Brain Institute, The University of Queensland, Australia.
⁶ Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany; Agaplesion Diakonieklinikum Rotenberg, Centre for Psychosocial Medicine, Elise-Averdieck-Straße 17, 27356 Rotenburg (Wümme), Germany.
⁷ Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany; Institute of Human Genetics, University of Bonn, Bonn, Germany.
⁸ Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany; Department of Psychiatry, University of Münster, Münster, Germany.
⁹ Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia.

PMID: 28624581
DOI: 10.1016/j.pnpbp.2017.06.010

Abstract

Introduction: Major depressive disorder (MDD) patients show impairments of cognitive functioning such as working memory (WM), and furthermore alterations during WM-fMRI tasks especially in frontal and parietal brain regions. The calculation of a polygenic risk score (PRS) can be used to describe the genetic influence on MDD, hence imaging genetic studies aspire to combine both genetics and neuroimaging data to identify the influence of genetic factors on brain functioning. We aimed to detect the effect of MDD-PRS on brain activation during a WM task measured with fMRI and expect healthy individuals with a higher PRS to be more resembling to MDD patients.

Method: In total, n=137 (80 men, 57 women, aged 34.5, SD=10.4years) healthy subjects performed a WM n-back task [0-back (baseline), 2-back and 3-back condition] in a 3T-MRI-tomograph. The sample was genotyped using the Infinium PsychArray BeadChip and a polygenic risk score was calculated for MDD using PGC MDD GWAS results.

Results: A lower MDD risk score was associated with increased activation in the bilateral middle occipital gyri (MOG), the bilateral middle frontal gyri (MFG) and the right precentral gyrus (PCG) during the 2-back vs. baseline condition. Moreover, a lower PRS was associated with increased brain activation during the 3-back vs. baseline condition in the bilateral cerebellum, the right MFG and the left inferior parietal lobule. A higher polygenic risk score was associated with hyperactivation in brain regions comprising the right MFG and the right supplementary motor area during the 3-back vs. 2-back condition.

Discussion: The results suggest that part of the WM-related brain activation patterns might be explained by genetic variants captured by the MDD-PRS. Furthermore we were able to detect MDD-associated activation patterns in healthy individuals depending on the MDD-PRS and the task complexity. Additional gene loci could contribute to these task-dependent brain activation patterns.

Keywords: Imaging genetics; Major depressive disorder; Polygenic risk for depression; Working memory; fMRI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Brain / diagnostic imaging
Brain / physiology*
Brain Mapping
Depressive Disorder, Major / genetics*
Female
Genetic Predisposition to Disease*
Genome-Wide Association Study
Genotyping Techniques
Humans
Magnetic Resonance Imaging
Male
Memory, Short-Term / physiology*
Multifactorial Inheritance*
Neuropsychological Tests
Regression Analysis