TY  - JOUR
PY  - 2022//
TI  - Genetics and brain transcriptomics of completed suicide
JO  - American journal of psychiatry
A1  - Tao, Ran
A1  - Radulescu, Eugenia
A1  - Chen, Qiang
A1  - Ursini, Gianluca
A1  - Punzi, Giovanna
A1  - Huuki, Louise A.
A1  - Di Carlo, Pasquale
A1  - Collado-Torres, Leonardo
A1  - Shin, Joo Heon
A1  - Catanesi, Roberto
A1  - Jaffe, Andrew E.
A1  - Hyde, Thomas M.
A1  - Kleinman, Joel E.
A1  - Mackay, Trudy F. C.
A1  - Weinberger, Daniel R.
SP  - 226
EP  - 241
VL  - 179
IS  - 3
N2  - 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. <br><br>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). <br><br>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. <br><br>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.<p />  <p>Language: en</p>
LA  - en
SN  - 0002-953X
UR  - http://dx.doi.org/10.1176/appi.ajp.2021.21030299
ID  - ref1
ER  -