New understanding of the neurobiology of impulse

Summary: A new gene-based scoring model could accurately detect which children are most at risk of developing impulsive behaviors.

source: McGill University

While not all impulsive behavior indicates mental illness, a wide range of mental health disorders often seen in adolescence, including depression and substance abuse, have been linked to impulsivity. So finding a way to identify and treat those who may be particularly prone to impulsivity early in life is especially important.

A group of researchers, led by researchers at McGill University, has developed a genetics-based score that can help identify, with a high degree of accuracy (greater than any currently used impulsivity scores), young children who are most at risk of impulsive behavior.

Their findings are particularly compelling because their finding was able to detect people at greater risk of impulsivity within three ethnically diverse community samples of children, from a group of nearly 6,000 children.

This discovery of a new indicator of impulsivity in early life could guide prevention strategies and programs for children and adolescents at risk for mental disorders. Additionally, by describing the function of the gene networks that comprise the result, the study could stimulate the development of new treatments in the future.

A shift in perspective leads to new results

The impulsive risk score was developed by looking at the co-expression of a number of genes in the prefrontal cortex and striatum, regions of the brain that play a role in decision-making and emotional regulation, among others.

Patricia Bellofo Silvera, associate professor in the Department of Psychiatry and a researcher at the Douglas Research Center and one of the lead authors on the latest paper in Molecular Psychiatry.

This discovery of a new indicator of impulsivity in early life could guide prevention strategies and programs for children and adolescents at risk for mental disorders. The image is in the public domain

“We got to the problem from the opposite direction, by focusing on a gene known to be associated with brain maturation in these two major regions and then looking for a network of other genes that are more closely related to it.”

It took a lot of fishing

This approach built on previous work in mouse models, led by Cecilia Flores, the paper’s co-lead author and full professor, in the Department of Psychiatry that identified the significance of a specific gene (known as DCC), which serves as a “guideline” that determines when and specifically where formation Dopamine cells in the brain and connections in the prefrontal cortex and striatum. This coordinated development is necessary for the maturity of impulse control.

But to create the new impulsivity score, it took a lot of research to narrow down the genes most closely associated with DCC.

“Our approach exploits the fact that genes function within complex networks that ultimately perform very precise biological functions. These so-called genetic networks have the property of being highly tissue-specific, so we set out to take an unbiased look at the sets of genes co-expressed with DCC in known brain regions. It plays an important role in supporting inhibitory control, says co-author Jose Maria Restrepo, Ph.D., a student in the Integrated Program in Neuroscience at McGill University.

“The findings underscore the importance of data sharing and open science,” Flores adds. Imagine if we had to collect this information in all these countries over the course of all these years. Our discovery was only possible because we had access to all of this data.”

About this genetics and impulse news

author: press office
source: McGill University
Contact: Press Office – McGill University
picture: The image is in the public domain

original search: open access.
DCC cortical gene co-expression networks as indicators of impulsivity in childrenWritten by Jose M. Restrepo-Lozano et al. Molecular Psychiatry


Summary

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This indicates a brain

DCC cortical gene co-expression networks as indicators of impulsivity in children

Deficiencies in inhibitory control are prevalent in many neuropsychiatric conditions. Communication—as well as connectivity—between cortical and limbic regions of the brain is central to eliciting inhibitory control behaviors, but early signs of impairment toward this behavioral trait have not been detected.

Progressive maturation of the prefrontal cortex (PFC), in particular the median cortical dopamine innervation, reflects the prolonged development of inhibitory control; Both are present early in life, but reach full maturity by early adulthood.

Evidence suggests Netrin-1/DCC Signaling pathway and associated gene networks in granular cortical development.

Here we investigated whether the expression-based polygenic score (ePRS) is based on corticolymphatic characteristics. DCC Co-gene expression networks correlate with impulsivity-related phenotypes in community samples of children.

We found that lower ePRS scores are associated with higher measures of impulsive choice in 6-year-olds tested in the information sampling task and impulsive action in 6- and 10-year-olds tested in the stop-signal task.

We also found that ePRS is a better overall predictor of impulsivity when compared to a conventional PRS score similar in size to ePRS (4515 SNPs in our discovery cohort) and derived from the most recent GWAS for ADHD. We suggest that corticosteroids DCCePRS can be used as a new type of marker for impulsivity-related phenotypes in children.

By adopting a systems biology approach based on common gene expression networks and genotype gene expression correlates (rather than genotype diseases), these results validate our methodology for creating multigene scores that are related to the overall biological function of tissue-specific gene networks.