Structural differences in the brain in adolescents may play a role in the early initiation of substance use

Structural differences in the brain in adolescents may play a role in the early initiation of substance use

A National Institutes of Health (NIH)-funded study of nearly 10,000 adolescents has found significant differences in the brain structure of those who used substances before the age of 15 compared to those who did not. Many of these structural differences in the brain appeared to be present in childhood before any substance use, suggesting that they, along with genetic, environmental and other neurological factors, may play a role in the risk of substance use later in life.

This adds to some emerging evidence that a person's brain structure, along with their unique genetics, environmental influences, and interactions between these factors, can influence the level of risk and resilience to substance use and addiction. Understanding the complex interplay between the factors that contribute to and protect against drug use is critical to informing effective prevention measures and providing support to those who may be most at risk.”

Nora Volkow MD, Director of NIDA

Of the 3,460 adolescents who started using drugs before age 15, most (90.2%) reported trying alcohol, with significant overlap with nicotine and/or cannabis use; 61.5% and 52.4% of children who started with nicotine and cannabis, respectively, also reported starting with alcohol. Substance initiation was associated with a variety of brain-wide (global) and more regional structural differences, primarily affecting the cortex, some of which were substance-specific. While these data could one day serve as the basis for clinical prevention strategies, the researchers emphasize that brain structure alone cannot predict substance use in adolescence and that these data should not be used as a diagnostic tool.

The study, published inJAMA network openedused data from the Adolescent Brain Cognitive Development Study (ABCD Study), the largest longitudinal study of brain development and health in children and adolescents in the United States, supported by the NIH's National Institute on Drug Abuse (NIDA) and nine other institutes, centers, and offices.

Using data from the ABCD study, researchers at Washington University in St. Louis evaluated MRI scans of 9,804 U.S. children ages 9 to 11 — at baseline — and followed participants over three years to determine whether certain aspects of brain structure captured in the baseline MRIs were associated with early substance initiation. They monitored alcohol, nicotine and/or cannabis use, the most common substances used in early adolescence, as well as use of other illicit substances. Researchers compared MRIs from 3,460 participants who reported substance use before age 15 between 2016 and 2021 with those who did not (6,344).

They assessed both global and regional differences in brain structure, examining measures such as volume, thickness, depth of brain folds and surface area, particularly in the cerebral cortex. The cortex is the outermost layer of the brain, densely packed with neurons and responsible for many higher-level processes, including learning, sensation, memory, language, emotions and decision-making. Specific features and differences in these structures—measured by thickness, surface area, and volume—have been linked to variability in cognitive abilities and neurological diseases.

Researchers identified five differences in brain structure at a global level between those who reported substance use before age 15 and those who did not. These included larger total brain volume and larger subcortical volume in those indicating substance initiation. At the regional level, an additional 39 differences in brain structure were found, with approximately 56% of the regional differences affecting cortical thickness. Some structural differences in the brain also appeared to be due to the type of substance used.

In a post hoc analysis, the researchers found that many of these brain differences remained even after excluding those participants who reported substance initiation before their baseline MRIs were collected. The resulting comparison was between those who reported no substance use initiation and a subgroup of 1,203 participants in the substance use initiation group who had no substance use experience when their MRIs were first collected. The results of this secondary analysis suggest that some of these structural differences in the brain may predate substance use, challenging the interpretation that such differences are caused only by substance exposure and suggesting an area for further investigation.

While some of the brain regions where differences have been identified have been linked to sensation-seeking and impulsivity, the researchers note that more work is needed to understand how these structural differences may impact differences in brain function or behavior. They also emphasize that the interplay between genetics, environment, brain structure, prenatal environment and behavioral influences influence behavior.

Another recent analysis of data from the University of Michigan's ABCD study demonstrates this interplay, showing that patterns of functional brain connectivity in early adolescence can predict the onset of substance use in adolescence and that these trajectories were likely influenced by exposure to pollution.

Future studies will be critical to determine how initial differences in brain structure may change as children age and with continued substance use or the development of a substance use disorder.

“Through the ABCD study, we have a robust and large database of longitudinal data that goes beyond previous neuroimaging research and understands the bidirectional relationship between brain structure and substance use,” said Alex Miller, Ph.D., corresponding author of the study and an assistant professor of psychiatry at Indiana University. “The hope is that these types of studies, coupled with other data on environmental exposures and genetic risks, could help change the way we think about the development of substance use disorders and provide more accurate models of addiction in the future.”

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