A study of nearly 10,000 adolescents funded by the National Institutes of Health (NIH) has identified clear differences in the brain structures of those who used substances before age 15 compared to those who did not. Many of these brain structural differences appeared to exist in childhood before any substance use, suggesting that they may play a role in the risk of substance use onset later in life, along with genetic, environmental factors and other neurological factors.
“This adds to some emerging evidence that an individual’s brain structure, along with their unique genetics, environmental exposures, and interactions between these factors, can affect their level of risk and resilience to substance use and addiction,” said Nora Volkow MD, director of NIDA. . “Understanding the complex interplay between factors that contribute to and protect against drug use is crucial to informing effective prevention interventions and providing support to those who may be most vulnerable.”
Among the 3,460 adolescents who initiated substance use before age 15, the majority (90.2%) reported trying alcohol, with considerable overlap with nicotine and/or cannabis use; 61.5% and 52.4% of children who started using nicotine and cannabis, respectively, also reported starting to drink alcohol. Substance initiation was associated with a variety of brain-wide (global) structural differences, as well as more regional structural differences primarily involving the cortex, some of which were substance-specific. While this data could one day help inform clinical prevention strategies, the researchers emphasize that brain structure alone cannot predict substance use during adolescence, and that these data should not be used as a diagnostic tool.
The study, published in Open JAMA Networkused data from the Adolescent Cognitive Brain Development Study (ABCD Study), the largest longitudinal study of brain development and health in children and adolescents in the United States, which is supported by the National Institute on Drug Abuse ( NIDA) of the NIH and nine other institutes, centers and offices.
Using data from the ABCD study, researchers at Washington University in St. Louis evaluated MRIs taken from 9,804 children across the United States when they were ages 9 to 11 (at “baseline”) and followed the participants for three years to determine whether certain aspects of brain structure captured on baseline MRIs were associated with early substance onset. They monitored the use of alcohol, nicotine and/or cannabis, the most common substances used in early adolescence, as well as the use of other illicit substances. Researchers compared MRIs of 3,460 participants who reported initiating substances before age 15 between 2016 and 2021 with those who did not (6,344).
They assessed both global and regional differences in brain structure, looking at measurements such as volume, thickness, depth of brain folds, and surface area, primarily in the cerebral cortex. The cortex is the outermost layer of the brain, packed with neurons and responsible for many higher-level processes, including learning, sensations, memory, language, emotions, and decision-making. Specific characteristics and differences in these structures (as measured by thickness, surface area, and volume) have been linked to variability in cognitive abilities and neurological conditions.
The researchers identified five global brain structural differences between those who reported initiating substances before age 15 and those who did not. These included greater total brain volume and greater subcortical volume in those who indicated substance initiation. An additional 39 differences in brain structure were found at the regional level, with approximately 56% of the regional variation involving cortical thickness. Some brain structural differences also seemed unique to the type of substance used.
In a post-hoc analysis, the researchers found that many of these brain differences still remained even after removing participants who reported initiating substances before the collection of their baseline MRIs. 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 did not have any substance use experience when their resonances were first captured. magnetic. The results of this secondary analysis suggest that some of these brain structural differences may exist prior to any substance use, challenging the interpretation that such differences are only driven by substance exposure and pointing to an area for further research.
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 delineate how these structural differences may translate into differences in brain function or behaviors. . They also emphasize that the interaction between genetics, environment, brain structure, prenatal environment, and behavioral influence affect behaviors.
Another recent analysis of data from the ABCD study conducted by the University of Michigan demonstrates this interaction, showing that patterns of functional brain connectivity in early adolescence could predict the onset of substance use in youth, and that these trajectories were likely influenced by exposure to pollution.
Future studies will be crucial to determine how initial differences in brain structure may change as children grow older and with continued substance use or the development of a substance use disorder.
“Through the ABCD study, we have a large, robust database of longitudinal data to go beyond previous neuroimaging research to understand the bidirectional relationship between brain structure and substance use,” said Alex Miller, Ph. D., corresponding author of the study and assistant professor of psychiatry at Indiana University. “The hope is that these types of studies, along with other data on environmental exposures and genetic risk, can help change the way we think about the development of substance use disorders and inform more accurate models of addiction in the future. “.