Academic Journal
Genetics and Brain Transcriptomics of Completed Suicide
| العنوان: | Genetics and Brain Transcriptomics of Completed Suicide |
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| المؤلفون: | Giovanna Punzi, Gianluca Ursini, Qiang Chen, Eugenia Radulescu, Ran Tao, Louise A. Huuki, Pasquale Di Carlo, Leonardo Collado-Torres, Joo Heon Shin, Roberto Catanesi, Andrew E. Jaffe, Thomas M. Hyde, Joel E. Kleinman, Trudy F. C. Mackay, Daniel R. Weinberger |
| المساهمون: | Punzi, Giovanna, Ursini, Gianluca, Chen, Qiang, Radulescu, Eugenia, Tao, Ran, Huuki, Louise A., DI CARLO, Pasquale, Collado-Torres, Leonardo, Heon Shin, Joo, Catanesi, Roberto, Jaffe, Andrew E., Hyde, Thomas M., Kleinman, Joel E., Mackay, Trudy F. C., Weinberger, Daniel R. |
| سنة النشر: | 2022 |
| المجموعة: | Università degli Studi di Bari Aldo Moro: CINECA IRIS |
| مصطلحات موضوعية: | Genomic Risk, Mitochondria, Postmortem Brain, Purinergic Signaling, RNA Sequencing, Suicide Method |
| الوصف: | Objective: The authors sought to study the transcriptomic and genomic features of completed suicide by parsing the method chosen, to capture molecular correlates of the distinctive frame of mind of individuals who die by suicide, while reducing heterogeneity. Methods: The authors analyzed gene expression (RNA sequencing) from postmortem dorsolateral prefrontal cortex of patients who died by suicide with violent compared with nonviolent means, nonsuicide patients with the same psychiatric disorders, and a neurotypical group (total N5329). They then examined genomic risk scores (GRSs) for each psychiatric disorder included, and GRSs for cognition (IQ) and for suicide attempt, testing how they predict diagnosis or traits (total N5888). Results: Patients who died by suicide by violent means showed a transcriptomic pattern remarkably divergent from each of the other patient groups but less from the neurotypical group; consistently, their genomic profile of risk was relatively low for their diagnosed illness as well as for suicide attempt, and relatively high for IQ: they were more similar to the neurotypical group than to other patients. Differentially expressed genes (DEGs) associated with patients who died by suicide by violent means pointed to purinergic signaling in microglia, showing similarities to a genome-wide association study of Drosophila aggression. Weighted gene coexpression network analysis revealed that these DEGs were coexpressed in a context of mitochondrial metabolic activation unique to suicide by violent means. Conclusions: These findings suggest that patients who die by suicide by violent means are in part biologically separable from other patients with the same diagnoses, and their behavioral outcome may be less dependent on genetic risk for conventional psychiatric disorders and be associated with an alteration of purinergic signaling and mitochondrial metabolism. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/35236118; info:eu-repo/semantics/altIdentifier/wos/WOS:000785967200009; volume:179; issue:3; firstpage:226; lastpage:241; numberofpages:16; journal:THE AMERICAN JOURNAL OF PSYCHIATRY; https://hdl.handle.net/11586/528640 |
| DOI: | 10.1176/appi.ajp.2021.21030299 |
| الاتاحة: | https://hdl.handle.net/11586/528640 https://doi.org/10.1176/appi.ajp.2021.21030299 https://psychiatryonline.org/doi/10.1176/appi.ajp.2021.21030299 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.17AC6C8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1176/appi.ajp.2021.21030299 |
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