Dataset Information

Genetics and Brain Transcriptomics of Completed Suicide.

ABSTRACT:

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 N=329). 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 N=888).

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.

SUBMITTER: Punzi G

PROVIDER: S-EPMC8908792 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Genetics and Brain Transcriptomics of Completed Suicide.

Punzi Giovanna G Ursini Gianluca G Chen Qiang Q Radulescu Eugenia E Tao Ran R Huuki Louise A LA Di Carlo Pasquale P Collado-Torres Leonardo L Shin Joo Heon JH Catanesi Roberto R Jaffe Andrew E AE Hyde Thomas M TM Kleinman Joel E JE Mackay Trudy F C TFC Weinberger Daniel R DR

The American journal of psychiatry 20220301 3

<h4>Objective</h4>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.<h4>Methods</h4>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 psychi ...[more]

PMID: 35236118

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Dataset Information

Genetics and Brain Transcriptomics of Completed Suicide.

Objective

Methods

Results

Conclusions

Publications

Genetics and Brain Transcriptomics of Completed Suicide.

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