Association between mitochondria-related genes and cognitive performance in the PsyCourse Study

Mojtaba Oraki Kohshour; Eva C Schulte; Urs Heilbronner; Monika Budde; Janos L Kalman; Fanny Senner; Maria Heilbronner; Daniela Reich-Erkelenz; Sabrina K Schaupp; Thomas Vogl; Kristina Adorjan; Ion-George Anghelescu; Volker Arolt; Bernhardt T Baune; Udo Dannlowski; Detlef Dietrich; Andreas Fallgatter; Christian Figge; Markus Jäger; Fabian U Lang; Georg Juckel; Carsten Konrad; Jens Reimer; Eva Z Reininghaus; Max Schmauß; Carsten Spitzer; Martin von Hagen; Jens Wiltfang; Jörg Zimmermann; Till F M Andlauer; Markus M Nöthen; Franziska Degenhardt; Andreas J Forstner; Marcella Rietschel; Stephanie H Witt; Andre Fischer; Peter Falkai; Sergi Papiol; Thomas G Schulze

doi:10.1016/j.jad.2023.01.013

Association between mitochondria-related genes and cognitive performance in the PsyCourse Study

J Affect Disord. 2023 Mar 15:325:1-6. doi: 10.1016/j.jad.2023.01.013. Epub 2023 Jan 6.

Authors

Mojtaba Oraki Kohshour¹, Eva C Schulte², Urs Heilbronner³, Monika Budde³, Janos L Kalman², Fanny Senner², Maria Heilbronner³, Daniela Reich-Erkelenz³, Sabrina K Schaupp³, Thomas Vogl³, Kristina Adorjan², Ion-George Anghelescu⁴, Volker Arolt⁵, Bernhardt T Baune⁶, Udo Dannlowski⁵, Detlef Dietrich⁷, Andreas Fallgatter⁸, Christian Figge⁹, Markus Jäger¹⁰, Fabian U Lang¹⁰, Georg Juckel¹¹, Carsten Konrad¹², Jens Reimer¹³, Eva Z Reininghaus¹⁴, Max Schmauß¹⁵, Carsten Spitzer¹⁶, Martin von Hagen¹⁷, Jens Wiltfang¹⁸, Jörg Zimmermann¹⁹, Till F M Andlauer²⁰, Markus M Nöthen²¹, Franziska Degenhardt²¹, Andreas J Forstner²², Marcella Rietschel²³, Stephanie H Witt²³, Andre Fischer²⁴, Peter Falkai²⁵, Sergi Papiol²⁶, Thomas G Schulze²⁷

Affiliations

¹ Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany; Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
² Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
³ Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.
⁴ Department of Psychiatry and Psychotherapy, Mental Health Institute Berlin, Berlin 14050, Germany.
⁵ Institute for Translational Psychiatry, University of Münster, Münster 48149, Germany.
⁶ Department of Psychiatry, University of Münster, Münster 48149, Germany; Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Australia; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
⁷ AMEOS Clinical Center Hildesheim, Hildesheim 31135, Germany; Center for Systems Neuroscience (ZSN), Hannover 30559, Germany; Department of Psychiatry, Medical School of Hannover, Hannover 30625, Germany.
⁸ Department of Psychiatry and Psychotherapy, Tübingen Center for Mental Health (TüCMH), University of Tübingen, Tübingen 72076, Germany.
⁹ Karl-Jaspers Clinic, European Medical School Oldenburg-Groningen, Oldenburg 26160, Germany.
¹⁰ Department of Psychiatry II, Ulm University, Bezirkskrankenhaus Günzburg, Günzburg 89312, Germany.
¹¹ Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, Bochum 44791, Germany.
¹² Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum, Rotenburg 27356, Germany.
¹³ Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany; Department of Psychiatry, Health North Hospital Group, Bremen 28102, Germany.
¹⁴ Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz 8036, Austria.
¹⁵ Clinic for Psychiatry, Psychotherapy and Psychosomatics, Augsburg University, Medical Faculty, Bezirkskrankenhaus Augsburg, Germany.
¹⁶ Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Rostock, Rostock 18147, Germany.
¹⁷ Clinic for Psychiatry and Psychotherapy, Clinical Center Werra-Meißner, Eschwege 37269, Germany.
¹⁸ Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen 37075, Germany; German Center for Neurodegenerative Diseases (DZNE), Göttingen 37075, Germany; iBiMED, Medical Sciences Department, University of Aveiro, Aveiro 3810-193, Portugal.
¹⁹ Psychiatrieverbund Oldenburger Land gGmbH, Karl-Jaspers-Klinik, Bad Zwischenahn 26160, Germany.
²⁰ Department of Neurology, University Hospital rechts der Isar, School of Medicine, Technical University of Munich, Munich 81675, Germany.
²¹ Institute of Human Genetics, University of Bonn School of Medicine & University Hospital Bonn, Bonn 53127, Germany.
²² Institute of Human Genetics, University of Bonn School of Medicine & University Hospital Bonn, Bonn 53127, Germany; Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich 52428, Germany.
²³ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim 68159, Germany.
²⁴ German Center of Neurodegenerative Diseases, University of Göttingen, Göttingen 37075, Germany.
²⁵ Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
²⁶ Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany. Electronic address: Sergi.Papiol@med.uni-muenchen.de.
²⁷ Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany; Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 36621676
DOI: 10.1016/j.jad.2023.01.013

Abstract

Background: Mitochondria generate energy through oxidative phosphorylation (OXPHOS). The function of key OXPHOS proteins can be altered by variation in mitochondria-related genes, which may increase the risk of mental illness. We investigated the association of mitochondria-related genes and their genetic risk burden with cognitive performance.

Methods: We leveraged cross-sectional data from 1320 individuals with a severe psychiatric disorder and 466 neurotypical individuals from the PsyCourse Study. The cognitive tests analyzed were the Trail-Making Test, Verbal Digit Span Test, Digit-Symbol Test, and Multiple Choice Vocabulary Intelligence Test. Association analyses between the cognitive tests, and single-nucleotide polymorphisms (SNPs) mapped to mitochondria-related genes, and their polygenic risk score (PRS) for schizophrenia (SCZ) were performed with PLINK 1.9 and R program.

Results: We found a significant association (FDR-adjusted p < 0.05) in the Cytochrome C Oxidase Assembly Factor 8 (COA8) gene locus of the OXPHOS pathway with the Verbal Digit Span (forward) test. Mitochondrial PRS was not significantly associated with any of the cognitive tests.

Limitations: Moderate statistical power due to relatively small sample size.

Conclusions: COA8 encodes a poorly characterized mitochondrial protein involved in apoptosis. Here, this gene was associated with the Verbal Digit Span (forward) test, which evaluates short-term memory. Our results warrant replication and may lead to better understanding of cognitive impairment in mental disorders.

Keywords: Brain disorders; COA8; Cognition; Mitochondria; Oxidative phosphorylation; Short-term memory.

Publication types

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

MeSH terms

Cognition
Cognitive Dysfunction* / complications
Cognitive Dysfunction* / genetics
Cross-Sectional Studies
Humans
Mitochondria / genetics
Neuropsychological Tests
Schizophrenia* / complications