Regulation of impulsive and aggressive behaviours by a novel lncRNA

Mol Psychiatry. 2021 Aug;26(8):3751-3764. doi: 10.1038/s41380-019-0637-4. Epub 2020 Jan 6.


High impulsive and aggressive traits associate with poor behavioural self-control. Despite their importance in predicting behavioural negative outcomes including suicide, the molecular mechanisms underlying the expression of impulsive and aggressive traits remain poorly understood. Here, we identified and characterized a novel long noncoding RNA (lncRNA), acting as a regulator of the monoamine oxidase A (MAOA) gene in the brain, and named it MAOA-associated lncRNA (MAALIN). Our results show that in the brain of suicide completers, MAALIN is regulated by a combination of epigenetic mechanisms including DNA methylation and chromatin modifications. Elevated MAALIN in the dentate gyrus of impulsive-aggressive suicides was associated with lower MAOA expression. Viral overexpression of MAALIN in neuroprogenitor cells decreased MAOA expression while CRISPR-mediated knock out resulted in elevated MAOA expression. Using viral-mediated gene transfer, we confirmed that MAALIN in the hippocampus significantly decreases MAOA expression and exacerbates the expression of impulsive-aggressive behavioural traits in CD1 aggressive mice. Overall, our findings suggest that variations in DNA methylation mediate the differential expression of a novel lncRNA that acts on MAOA expression to regulate impulsive-aggressive behaviours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression*
  • Animals
  • Genotype
  • Humans
  • Impulsive Behavior*
  • Mice
  • Monoamine Oxidase / genetics
  • RNA, Long Noncoding* / genetics
  • Suicide*


  • RNA, Long Noncoding
  • Monoamine Oxidase