Meike D Hettwer1,2,3,4, Thomas M Lancaster5,6, Eva Raspor1, Peter K Hahn1, Nina Roth Mota7,8, Wolf Singer9,10,11, Andreas Reif1, David E J Linden6,12, Robert A Bittner1,9. 1. Department of Psychiatry, Psychosomatic Medicine, and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany. 2. Max Planck School of Cognition, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany. 3. Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Jülich, Germany. 4. Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 5. School of Psychology, Bath University, Bath, UK. 6. MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK. 7. Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands. 8. Department of Psychiatry, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands. 9. Ernst Strüngmann Institute for Neuroscience (ESI) in Cooperation with Max Planck Society, Frankfurt am Main, Germany. 10. Max Planck Institute for Brain Research (MPI BR), Frankfurt am Main, Germany. 11. Frankfurt Institute for Advanced Studies (FIAS), Frankfurt am Main, Germany. 12. School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
Abstract
INTRODUCTION: Illuminating neurobiological mechanisms underlying the protective effect of recently discovered common genetic resilience variants for schizophrenia is crucial for more effective prevention efforts. Current models implicate adaptive neuroplastic changes in the visual system and their pro-cognitive effects as a schizophrenia resilience mechanism. We investigated whether common genetic resilience variants might affect brain structure in similar neural circuits. METHOD: Using structural magnetic resonance imaging, we measured the impact of an established schizophrenia polygenic resilience score (PRSResilience) on cortical volume, thickness, and surface area in 101 healthy subjects and in a replication sample of 33 224 healthy subjects (UK Biobank). FINDING: We observed a significant positive whole-brain correlation between PRSResilience and cortical volume in the right fusiform gyrus (FFG) (r = 0.35; P = .0004). Post-hoc analyses in this cluster revealed an impact of PRSResilience on cortical surface area. The replication sample showed a positive correlation between PRSResilience and global cortical volume and surface area in the left FFG. CONCLUSION: Our findings represent the first evidence of a neurobiological correlate of a genetic resilience factor for schizophrenia. They support the view that schizophrenia resilience emerges from strengthening neural circuits in the ventral visual pathway and an increased capacity for the disambiguation of social and nonsocial visual information. This may aid psychosocial functioning, ameliorate the detrimental effects of subtle perceptual and cognitive disturbances in at-risk individuals, and facilitate coping with the cognitive and psychosocial consequences of stressors. Our results thus provide a novel link between visual cognition, the vulnerability-stress concept, and schizophrenia resilience models.
INTRODUCTION: Illuminating neurobiological mechanisms underlying the protective effect of recently discovered common genetic resilience variants for schizophrenia is crucial for more effective prevention efforts. Current models implicate adaptive neuroplastic changes in the visual system and their pro-cognitive effects as a schizophrenia resilience mechanism. We investigated whether common genetic resilience variants might affect brain structure in similar neural circuits. METHOD: Using structural magnetic resonance imaging, we measured the impact of an established schizophrenia polygenic resilience score (PRSResilience) on cortical volume, thickness, and surface area in 101 healthy subjects and in a replication sample of 33 224 healthy subjects (UK Biobank). FINDING: We observed a significant positive whole-brain correlation between PRSResilience and cortical volume in the right fusiform gyrus (FFG) (r = 0.35; P = .0004). Post-hoc analyses in this cluster revealed an impact of PRSResilience on cortical surface area. The replication sample showed a positive correlation between PRSResilience and global cortical volume and surface area in the left FFG. CONCLUSION: Our findings represent the first evidence of a neurobiological correlate of a genetic resilience factor for schizophrenia. They support the view that schizophrenia resilience emerges from strengthening neural circuits in the ventral visual pathway and an increased capacity for the disambiguation of social and nonsocial visual information. This may aid psychosocial functioning, ameliorate the detrimental effects of subtle perceptual and cognitive disturbances in at-risk individuals, and facilitate coping with the cognitive and psychosocial consequences of stressors. Our results thus provide a novel link between visual cognition, the vulnerability-stress concept, and schizophrenia resilience models.
Authors: Murray B Stein; Karmel W Choi; Sonia Jain; Laura Campbell-Sills; Chia-Yen Chen; Joel Gelernter; Feng He; Steven G Heeringa; Adam X Maihofer; Caroline Nievergelt; Matthew K Nock; Stephan Ripke; Xiaoying Sun; Ronald C Kessler; Jordan W Smoller; Robert J Ursano Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2019-05-13 Impact factor: 3.568
Authors: Nadine Revheim; Cheryl M Corcoran; Elisa Dias; Esther Hellmann; Antigona Martinez; Pamela D Butler; Jonathan M Lehrfeld; Joanna DiCostanzo; Jennifer Albert; Daniel C Javitt Journal: Am J Psychiatry Date: 2014-09 Impact factor: 18.112
Authors: Jonathan L Hess; Daniel S Tylee; Manuel Mattheisen; Anders D Børglum; Thomas D Als; Jakob Grove; Thomas Werge; Preben Bo Mortensen; Ole Mors; Merete Nordentoft; David M Hougaard; Jonas Byberg-Grauholm; Marie Bækvad-Hansen; Tiffany A Greenwood; Ming T Tsuang; David Curtis; Stacy Steinberg; Engilbert Sigurdsson; Hreinn Stefánsson; Kári Stefánsson; Howard J Edenberg; Peter Holmans; Stephen V Faraone; Stephen J Glatt Journal: Mol Psychiatry Date: 2019-09-06 Impact factor: 15.992