Year: 2020
Type: article
Study design: Observational Study
Abstract: Mismatch negativity (MMN) is a differential electrophysiological response measuring cortical adaptability to unpredictable stimuli. MMN is consistently attenuated in patients with psychosis. However, the genetics of MMN are uncharted, limiting the validation of MMN as a psychosis endophenotype. Here, we perform a transcriptome-wide association study of 728 individuals, which reveals 2 genes (FAM89A and ENGASE) whose expression in cortical tissues is associated with MMN. Enrichment analyses of neurodevelopmental expression signatures show that genes associated with MMN tend to be overexpressed in the frontal cortex during prenatal development but are significantly downregulated in adulthood. Endophenotype ranking value calculations comparing MMN and three other candidate psychosis endophenotypes (lateral ventricular volume and two auditory-verbal learning measures) find MMN to be considerably superior. These results yield promising insights into sensory processing in the cortex and endorse the notion of MMN as a psychosis endophenotype.
Source: Cell Reports
Authors: Anjali Bhat, Haritz Irizar, Johan Hilge Thygesen, Karoline Kuchenbaecker, Oliver Pain, Rick A. Adams, Eirini Zartaloudi, Jasmine Harju-Seppänen, Isabelle Austin-Zimmerman, Baihan Wang, Rebecca Muir, Ann Summerfelt, Xiaoming Michael Du, Heather Bruce, Patricio O’Donnell, Deepak P. Srivastava, Karl Friston, L. Elliot Hong, Mei-Hua Hall, Elvira Bramon
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: Pfizer, Harvard University, South London and Maudsley NHS Foundation Trust, Mental Health Research UK, Schizophrenia Research Fund, Wellcome Trust, Psychiatry Research Trust, National Institute for Health and Care Research, European Commission, Korea Health Industry Development Institute, National Institutes of Health, Horizon 2020 Framework Programme, Medical Research Council, Biotechnology and Biological Sciences Research Council, Horizon 2020, UCLH Biomedical Research Centre, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, National Cancer Institute, National Institute of Neurological Disorders and Stroke
Awards: G1000482210, WTCCC2 core activities., G173045874, G1767001012, The Role of Stress-Immune-Connectome Disruption in Mechanisms of Chinese Early Schizophrenia Spectrum, Using Genetics to Personalise Antipsychotic Treatment, Mechanisms of Oestrogenic Modulation of Neural Circuitry, G2692368831, G3221353860, MRC Centre for Neurodevelopmental Disorders, Towards Multisystem-Brain Successful Aging in Schizophrenia Spectrum, G4119729070, G436508962, Neurobiological Markers as Predictors of Later Functional Outcome in First Episode Psychosis, G6720140889, Finding psychosis subtypes using machine learning, clinical, genetic and multimodal imaging data, MRC Centre for Neurodevelopmental Disorders, WTCCC2 core activities., G7223858984, Functional architectures in the brain.
OpenAlex ID: W3136028441