Frontiers in Systems Neuroscience (Sep 2021)
Immune-Related Genetic Overlap Between Regional Gray Matter Reductions and Psychiatric Symptoms in Adolescents, and Gene-Set Validation in a Translational Model
- Lukas Penninck,
- El Chérif Ibrahim,
- Eric Artiges,
- Eric Artiges,
- Victor Gorgievski,
- Sylvane Desrivières,
- Severine Farley,
- Irina Filippi,
- Carlos E. A. de Macedo,
- Raoul Belzeaux,
- Raoul Belzeaux,
- Tobias Banaschewski,
- Arun L. W. Bokde,
- Erin Burke Quinlan,
- Herta Flor,
- Herta Flor,
- Antoine Grigis,
- Hugh Garavan,
- Penny Gowland,
- Andreas Heinz,
- Rüdiger Brühl,
- Frauke Nees,
- Frauke Nees,
- Frauke Nees,
- Dimitri Papadopoulos Orfanos,
- Tomáš Paus,
- Tomáš Paus,
- Luise Poustka,
- Juliane H. Fröhner,
- Michael N. Smolka,
- Henrik Walter,
- Robert Whelan,
- Julien Grenier,
- Gunter Schumann,
- Gunter Schumann,
- Gunter Schumann,
- Marie-Laure Paillère Martinot,
- Marie-Laure Paillère Martinot,
- Eleni T. Tzavara,
- Eleni T. Tzavara,
- Eleni T. Tzavara,
- Jean-Luc Martinot,
- for the IMAGEN Consortium
Affiliations
- Lukas Penninck
- Institut National de la Santé et de la Recherche Médicale, INSERM U1299 “Trajectoires Développementales en Psychiatrie”, Université Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, France
- El Chérif Ibrahim
- Aix Marseille Univ, CNRS, INT, Inst Neurosci Timone, Marseille, France
- Eric Artiges
- Institut National de la Santé et de la Recherche Médicale, INSERM U1299 “Trajectoires Développementales en Psychiatrie”, Université Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, France
- Eric Artiges
- EPS Barthelemy Durand, Etampes, France
- Victor Gorgievski
- University of Paris, CNRS, INCC, Paris, France
- Sylvane Desrivières
- Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King’s College London, London, United Kingdom
- Severine Farley
- University of Paris, CNRS, INCC, Paris, France
- Irina Filippi
- Institut National de la Santé et de la Recherche Médicale, INSERM U1299 “Trajectoires Développementales en Psychiatrie”, Université Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, France
- Carlos E. A. de Macedo
- University of Paris, CNRS, INCC, Paris, France
- Raoul Belzeaux
- Aix Marseille Univ, CNRS, INT, Inst Neurosci Timone, Marseille, France
- Raoul Belzeaux
- AP-HM, Hôpital Sainte Marguerite, Pôle de Psychiatrie Universitaire Solaris, Marseille, France
- Tobias Banaschewski
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Arun L. W. Bokde
- Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
- Erin Burke Quinlan
- Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King’s College London, London, United Kingdom
- Herta Flor
- Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Herta Flor
- 0Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany
- Antoine Grigis
- 1NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France
- Hugh Garavan
- 2Department of Psychiatry and Psychology, University of Vermont, Burlington, VT, United States
- Penny Gowland
- 3Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom
- Andreas Heinz
- 4Department of Psychiatry and Psychotherapy, CCM, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Rüdiger Brühl
- 5Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Germany
- Frauke Nees
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Frauke Nees
- Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Frauke Nees
- 6Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, Germany
- Dimitri Papadopoulos Orfanos
- 1NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France
- Tomáš Paus
- 7Department of Psychiatry, Faculty of Medicine and Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, QC, Canada
- Tomáš Paus
- 8Department of Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada
- Luise Poustka
- 9Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, Göttingen, Germany
- Juliane H. Fröhner
- 0Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany
- Michael N. Smolka
- 0Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany
- Henrik Walter
- 4Department of Psychiatry and Psychotherapy, CCM, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Robert Whelan
- 1School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland
- Julien Grenier
- 2Université de Paris, INSERM UMRS 1124, Paris, France
- Gunter Schumann
- Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King’s College London, London, United Kingdom
- Gunter Schumann
- 3PONS Research Group, Department of Psychiatry and Psychotherapy, Humboldt University, Berlin and Leibniz Institute for Neurobiology, Magdeburg, Germany
- Gunter Schumann
- 4Institute for Science and Technology of Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, China
- Marie-Laure Paillère Martinot
- Institut National de la Santé et de la Recherche Médicale, INSERM U1299 “Trajectoires Développementales en Psychiatrie”, Université Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, France
- Marie-Laure Paillère Martinot
- 5AP-HP.Sorbonne Université, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France
- Eleni T. Tzavara
- University of Paris, CNRS, INCC, Paris, France
- Eleni T. Tzavara
- AP-HM, Hôpital Sainte Marguerite, Pôle de Psychiatrie Universitaire Solaris, Marseille, France
- Eleni T. Tzavara
- 6Fondation Fondamental, Créteil, France
- Jean-Luc Martinot
- Institut National de la Santé et de la Recherche Médicale, INSERM U1299 “Trajectoires Développementales en Psychiatrie”, Université Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, France
- for the IMAGEN Consortium
- DOI
- https://doi.org/10.3389/fnsys.2021.725413
- Journal volume & issue
-
Vol. 15
Abstract
Adolescence is a period of vulnerability for the maturation of gray matter (GM) and also for the onset of psychiatric disorders such as major depressive disorder (MDD), bipolar disorder and schizophrenia. Chronic neuroinflammation is considered to play a role in the etiology of these illnesses. However, the involvement of neuroinflammation in the observed link between regional GM volume reductions and psychiatric symptoms is not established yet. Here, we investigated a possible common immune-related genetic link between these two phenomena in european adolescents recruited from the community. Hippocampal and medial prefrontal cortex (mPFC) were defined a priori as regions of interest (ROIs). Their GM volumes were extracted in 1,563 14-year-olds from the IMAGEN database. We found a set of 26 SNPs that correlated with the hippocampal volumes and 29 with the mPFC volumes at age 14. We formed two ROI-Related Immune-gene scores (RRI) with the inflammation SNPs that correlated to hippocampal GM volume and to mPFC GM volume. The predictive ability of both RRIs with regards to the presence of psychiatric symptoms at age 18 was investigated by correlating the RRIs with psychometric questionnaires obtained at age 18. The RRIs (but not control scores constructed with random SNPs) correlated with the presence of depressive symptoms, positive psychotic symptoms, and externalizing symptoms in later adolescence. In addition, the effect of childhood maltreatment, one of the major environmental risk factors for depression and other mental disorders, interacted with the RRI effect. We next sought to validate this finding by investigating our set of inflammatory genes in a translational animal model of early life adversity. Mice were subjected to a protocol of maternal separation at an early post-natal age. We evaluated depressive behaviors in separated and non-separated mice at adolescence and their correlations with the concomitant expression of our genes in whole blood samples. We show that in mice, early life adversity affected the expression of our set of genes in peripheral blood, and that levels of expression correlated with symptoms of negative affect in adolescence. Overall, our translational findings in adolescent mice and humans provide a novel validated gene-set of immune-related genes for further research in the early stages of mood disorders.
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