Tiziana Quarto, Annalisa Lella, Pasquale Di Carlo, Antonio Rampino, Vittoria Paladini, Marco Papalino, Raffaella Romano, Leonardo Fazio, Daniela Marvulli, Teresa Popolizio, Giuseppe Blasi, Giulio Pergola, Alessandro Bertolino
{"title":"杏仁核对愤怒面孔反应的遗传性及其与miR-137精神分裂症风险基因座的可复制关联。","authors":"Tiziana Quarto, Annalisa Lella, Pasquale Di Carlo, Antonio Rampino, Vittoria Paladini, Marco Papalino, Raffaella Romano, Leonardo Fazio, Daniela Marvulli, Teresa Popolizio, Giuseppe Blasi, Giulio Pergola, Alessandro Bertolino","doi":"10.1503/jpn.230013","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Among healthy participants, the interindividual variability of brain response to facial emotions is associated with genetic variation, including common risk variants for schizophrenia, a heritable brain disorder characterized by anomalies in emotion processing. We aimed to identify genetic variants associated with heritable brain activity during processing of facial emotions among healthy participants and to explore the impact of these identified variants among patients with schizophrenia.</p><p><strong>Methods: </strong>We conducted a data-driven stepwise study including samples of healthy twins, unrelated healthy participants and patients with schizophrenia. Participants approached or avoided pictures of faces with negative emotional valence during functional magnetic resonance imaging (fMRI).</p><p><strong>Results: </strong>We investigated 3 samples of healthy participants - including 28 healthy twin pairs, 289 unrelated healthy participants (genome-wide association study [GWAS] discovery sample) and 90 unrelated healthy participants (replication sample) - and 1 sample of 48 patients with schizophrenia. Among healthy twins, we identified the amygdala as the brain region with the highest heritability during processing of angry faces (heritability estimate 0.54, <i>p</i> < 0.001). Subsequent GWAS in both discovery and replication samples of healthy non-twins indicated that amygdala activity was associated with a polymorphism in the <i>miR-137</i> locus (rs1198575), a micro-RNA strongly involved in risk for schizophrenia. A significant effect in the same direction was found among patients with schizophrenia (<i>p</i> = 0.03).</p><p><strong>Limitations: </strong>The limited sample size available for GWAS analyses may require further replication of results.</p><p><strong>Conclusion: </strong>Our data-driven approach shows preliminary evidence that amygdala activity, as evaluated with our task, is heritable. Our genetic associations preliminarily suggest a role for <i>miR-137</i> in brain activity during explicit processing of facial emotions among healthy participants and patients with schizophrenia, pointing to the amygdala as a brain region whose activity is related to <i>miR-137</i>.</p>","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"48 5","pages":"E357-E366"},"PeriodicalIF":4.1000,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3c/0c/48-5-E357.PMC10521919.pdf","citationCount":"0","resultStr":"{\"title\":\"Heritability of amygdala reactivity to angry faces and its replicable association with the schizophrenia risk locus of <i>miR-137</i>.\",\"authors\":\"Tiziana Quarto, Annalisa Lella, Pasquale Di Carlo, Antonio Rampino, Vittoria Paladini, Marco Papalino, Raffaella Romano, Leonardo Fazio, Daniela Marvulli, Teresa Popolizio, Giuseppe Blasi, Giulio Pergola, Alessandro Bertolino\",\"doi\":\"10.1503/jpn.230013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Among healthy participants, the interindividual variability of brain response to facial emotions is associated with genetic variation, including common risk variants for schizophrenia, a heritable brain disorder characterized by anomalies in emotion processing. We aimed to identify genetic variants associated with heritable brain activity during processing of facial emotions among healthy participants and to explore the impact of these identified variants among patients with schizophrenia.</p><p><strong>Methods: </strong>We conducted a data-driven stepwise study including samples of healthy twins, unrelated healthy participants and patients with schizophrenia. Participants approached or avoided pictures of faces with negative emotional valence during functional magnetic resonance imaging (fMRI).</p><p><strong>Results: </strong>We investigated 3 samples of healthy participants - including 28 healthy twin pairs, 289 unrelated healthy participants (genome-wide association study [GWAS] discovery sample) and 90 unrelated healthy participants (replication sample) - and 1 sample of 48 patients with schizophrenia. Among healthy twins, we identified the amygdala as the brain region with the highest heritability during processing of angry faces (heritability estimate 0.54, <i>p</i> < 0.001). Subsequent GWAS in both discovery and replication samples of healthy non-twins indicated that amygdala activity was associated with a polymorphism in the <i>miR-137</i> locus (rs1198575), a micro-RNA strongly involved in risk for schizophrenia. A significant effect in the same direction was found among patients with schizophrenia (<i>p</i> = 0.03).</p><p><strong>Limitations: </strong>The limited sample size available for GWAS analyses may require further replication of results.</p><p><strong>Conclusion: </strong>Our data-driven approach shows preliminary evidence that amygdala activity, as evaluated with our task, is heritable. Our genetic associations preliminarily suggest a role for <i>miR-137</i> in brain activity during explicit processing of facial emotions among healthy participants and patients with schizophrenia, pointing to the amygdala as a brain region whose activity is related to <i>miR-137</i>.</p>\",\"PeriodicalId\":50073,\"journal\":{\"name\":\"Journal of Psychiatry & Neuroscience\",\"volume\":\"48 5\",\"pages\":\"E357-E366\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2023-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3c/0c/48-5-E357.PMC10521919.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Psychiatry & Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1503/jpn.230013\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/9/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Psychiatry & Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1503/jpn.230013","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/1 0:00:00","PubModel":"Print","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Heritability of amygdala reactivity to angry faces and its replicable association with the schizophrenia risk locus of miR-137.
Background: Among healthy participants, the interindividual variability of brain response to facial emotions is associated with genetic variation, including common risk variants for schizophrenia, a heritable brain disorder characterized by anomalies in emotion processing. We aimed to identify genetic variants associated with heritable brain activity during processing of facial emotions among healthy participants and to explore the impact of these identified variants among patients with schizophrenia.
Methods: We conducted a data-driven stepwise study including samples of healthy twins, unrelated healthy participants and patients with schizophrenia. Participants approached or avoided pictures of faces with negative emotional valence during functional magnetic resonance imaging (fMRI).
Results: We investigated 3 samples of healthy participants - including 28 healthy twin pairs, 289 unrelated healthy participants (genome-wide association study [GWAS] discovery sample) and 90 unrelated healthy participants (replication sample) - and 1 sample of 48 patients with schizophrenia. Among healthy twins, we identified the amygdala as the brain region with the highest heritability during processing of angry faces (heritability estimate 0.54, p < 0.001). Subsequent GWAS in both discovery and replication samples of healthy non-twins indicated that amygdala activity was associated with a polymorphism in the miR-137 locus (rs1198575), a micro-RNA strongly involved in risk for schizophrenia. A significant effect in the same direction was found among patients with schizophrenia (p = 0.03).
Limitations: The limited sample size available for GWAS analyses may require further replication of results.
Conclusion: Our data-driven approach shows preliminary evidence that amygdala activity, as evaluated with our task, is heritable. Our genetic associations preliminarily suggest a role for miR-137 in brain activity during explicit processing of facial emotions among healthy participants and patients with schizophrenia, pointing to the amygdala as a brain region whose activity is related to miR-137.
期刊介绍：
The Journal of Psychiatry & Neuroscience publishes papers at the intersection of psychiatry and neuroscience that advance our understanding of the neural mechanisms involved in the etiology and treatment of psychiatric disorders. This includes studies on patients with psychiatric disorders, healthy humans, and experimental animals as well as studies in vitro. Original research articles, including clinical trials with a mechanistic component, and review papers will be considered.
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