Association of a Noncoding RNA Postmortem With Suicide by Violent Means and In Vivo With Aggressive Phenotypes

Abstract

Objective: Previous findings suggest that differences in brain expression of a humanspecific long intergenic non-coding RNA (LINC01268; GRCh37/hg19: LOC285758) may be linked to aggressive behavior and suicide. The authors sought to replicate and extend these findings in a new sample, and translate the results to the behavioral level in living healthy subjects. Method:The authors examined RNA sequencing data in human brain to confirm the prior postmortem association of the lincRNA specifically with suicide by violent means. In addition, they used a genetic variant associated with LINC01268 expression to detect association with in vivo prefrontal physiology related to behavioral control.They finally performed weighted gene co-expression network analysis (WGCNA) and gene-ontology analysis to identify biological processes associated with a LINC01268 co-expression network. Results:In the replication sample, prefrontal expression of LINC01268 was again higher in suicides by violent means (N=65) than both non-suicides (N=78; 1.29e-06) and suicides by non-violent means (N=46; p=1.4e-06). In a living cohort, carriers of the minor allele of a SNP associated with increased LINC01268 expression in brain scored higher on a lifetime aggression questionnaire and show diminished engagement of prefrontal cortex (BA10) when viewing angry faces during fMRI.WGCNA highlighted the immune response.Conclusions: These results suggest that LINC01268 influences emotional regulation, aggressive behavior and suicide by violent means; the underlying biological dynamics may include modulation of genes potentially engaged in the immune response.

LINC01268 and CTB-31O20.2 as Prognostic and Functional Protective Immune Related lncRNAs in Glioblastoma

“…Transcriptome sequencing and qRT-PCR con rmed that lncRNA SMIM25 was high expression in cerebral cavernous malformations on the before study [42]. LINC01268 could in uence the emotional regulation, and was involved in gene regulation of potential immune response [43]. The alias of GS1-358P8.4 is PDK3, the study reported that high expressions of PDK3 were poor prognostic factors of acute myeloid leukemia [44].…”

Long-Term Impact of Social Isolation and Molecular Underpinnings

“…Since chronically isolated mice have altered behaviors toward other individuals, such as increased aggression but also blunted response to social novelty (Zelikowsky et al, 2018), it is possible that lncRNAs are important modulators of behavioral responses due to chronic social isolation in mammals. Consistently, aggressive behaviors have also been associated with changes in lncRNAs expression (Punzi et al, 2019;Labonté et al, 2020). The monoamine oxidase A (MAOA) associated ncRNA (MAALIN) is a lncRNA located in the 3 intergenic region separating the tail-to-tail oriented MAO genes A and B.…”

Non-Coding RNAs in Psychiatric Disorders and Suicidal Behavior

“…LOC28758 is located in the MARCKS gene, which was also found to be significantly highly expressed in violent suicides than non-suicides and non-violent suicides. In a recent study, the authors also examined lncRNA expression changes in dlPFC by RNA-seq (28). LINC01268 expression was significantly higher in suicide subjects compared to non-suicide subjects.…”

“…Brain expressed ncRNAs can also influence the development of psychiatric disorders such as schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD) as well as neurodegenerative disorders ( 11 , 19 , 23 , 26 , 27 ). More recently, their role in suicidal behavior has been postulated ( 28 – 30 ). The effects of ncRNA expression changes are not restricted to the type of psychiatric disorders but, to a large extent, to different brain regions.…”