A New Understanding of the Neurobiology of Impulsivity


Summary: A new genetic-based assessment model can accurately identify children at greatest risk of developing impulsive behavior.

Source: McGill University

While not all impulsive behavior is indicative of mental illness, a variety of mental health disorders common in adolescence, including depression and substance abuse, have been linked to impulsivity. Therefore, 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 McGill University scientists have developed a genetic-based score that could help identify, with a high degree of accuracy (greater than any impulsivity scores currently in use), young children most at risk of impulsive behavior .

Their results are particularly compelling because the score they developed was able to identify those at higher risk for impulsivity within three ethnically diverse community samples of children from a cohort of nearly 6,000 children.

This discovery of a novel early-life score for impulsivity may inform prevention strategies and programs for children and adolescents at risk for psychiatric disorders. In addition, by describing the function of the gene networks that make up the score, the study may stimulate the development of new therapies in the future.

A change of perspective leads to new insights

The Impulsivity Risk Score was developed by examining the co-expression of a number of genes in the prefrontal cortex and striatum, areas of the brain that play a role in decision-making and emotion regulation, among other things.

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“Typically, genetic approaches to identifying the neurobiological signature for impulsivity (or any other condition or disease) focus on identifying the variation of some genetic markers that might be responsible for the problem,” said Patricia Pelufo Silveira, associate professor in of the Department of Psychiatry and a researcher at the Douglas Research Center and one of the two senior authors of the recent publication in Molecular Psychiatry.

This shows the outlines of two heads
This discovery of a novel early-life score for impulsivity may inform prevention strategies and programs for children and adolescents at risk for psychiatric disorders. The image is in the public domain

“We approached the problem from the opposite direction, focusing on a gene known to be associated with brain maturation in these two key areas, and then looking for a network of other genes involved in were most closely associated with it.”

It hunted a lot

This approach was based on previous work in mouse models led by Cecilia Flores, co-senior author of the publication and full professor at the Department of Psychiatry, who had identified the importance of a particular gene (known as DCC) that acts as a “guidance signal” that determines , exactly when and where dopamine cells of the brain make connections in the prefrontal cortex and striatum. This coordinated development is essential for the maturation of impulse control.

But creating the new impulsivity score required a lot of hunting to narrow down the genes most closely associated with DCC.

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“Our approach exploits the fact that genes operate in complex networks that ultimately perform very precise biological functions. These so-called gene networks have the property of being very tissue-specific, so we started with an unbiased look at groups of genes co-expressed with DCC in brain regions known to play important roles in supporting inhibitory control,” says co-author Jose Maria Restrepo, a Ph.D. Student in the Integrated Program in Neuroscience at McGill University.

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

About this news from genetics and impulsivity research

Author: press office
Source: McGill University
Contact: Press Office – McGill University
Picture: The image is in the public domain

Original research: Open access.
“Corticolimbic DCC gene coexpression networks as predictors of impulsivity in children” by Jose M. Restrepo-Lozano et al. Molecular Psychiatry


abstract

See also

This shows a brain

Corticolimbic DCC gene coexpression networks as predictors of impulsivity in children

Inhibitory control deficits are common in several neuropsychiatric disorders. Communication—as well as connectivity—between corticolimbic regions of the brain are fundamental to triggering inhibitory control behavior, but early markers of susceptibility to this behavioral trait have yet to be discovered.

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The gradual maturation of the prefrontal cortex (PFC), particularly the mesocortical dopamine innervation, reflects the protracted development of inhibitory control; both are present early in life but reach full maturity in early adulthood.

Evidence points to the involvement of netrin-1/DCC Signaling pathway and its associated gene networks in corticolimbic development.

Here we investigated whether an expression-based polygenic score (ePRS) based on corticolimbic specific DCC Gene coexpression networks associate with impulsivity-related phenotypes in community samples of children.

We found that lower ePRS scores in 6-year-old children tested in the Information Sampling Task correlated with higher measurements of impulsive choice and in 6- and 10-year-old children tested in the Stop Signal Task impulsive actions.

We also found that the ePRS is a better overall predictor of impulsivity compared to a conventional PRS score comparable in size to the ePRS (4515 SNPs in our discovery cohort) derived from the latest GWAS for ADHD. We propose that the corticolimbic DCC-ePRS may serve as a novel marker of impulsivity-related phenotypes in children.

By adopting a systems biology approach based on gene coexpression networks and genotype-gene expression associations (rather than genotype-disease), these results validate our methodology to construct polygenic scores linked to the overall biological function of tissue-specific gene networks.



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