News — When studying substance use disorders, scientists had thought some of the effects on the brain could stem from use of the substances themselves: People start drinking alcohol in early teens, that alcohol has a neurotoxic effect on the developing brain that begets more alcohol drinking, and a similar dynamic occurs with other substances.
But research from Washington University in St. Louis turns that thinking around. Certain features of brain structure may be one of the factors that can contribute to substance use initiation.
WashU researchers in the department of Art & Sciences and School of Medicine studied the brain scans of nearly 10,000 children in the large-scale Adolescent Brain Cognitive Development (ABCD) Study. The idea was to compare results of scans between participants who did and did not go on to start trying substances in early teens. What they found were correlations between certain types of brain structure and those that do try substances before age 15.
“What we looked at was whether these neural differences precede any substance involvement essentially. And we do find that,” said Ryan Bogdan, ​dean's distinguished professor of psychological & brain sciences and co-author of this research, now published in JAMA Network Open.
In the research, Bogdan, along with first author Alex Miller, assistant professor of psychiatry now at Indiana University School of Medicine, and Arpana Agrawal, the James and Juanita Wittmer Professor in the Department of Psychiatry at WashU Medicine, highlighted a number of structural differences in the cortex, including the prefrontal cortex, that may contribute to trying substances in adolescence.
Researchers emphasized this is just one piece of a puzzle in the progression of substance use, including their early home environment, and the genetic building blocks that factor into brain structure from the get-go.
Agrawal added that the brain structure features that correlate with early initiation of substance use would not mean they can use those structures as a diagnostic tool. Instead, it gives researchers a start to pin down the many factors that may lead to substance use problems down the line.
“I think this is a clue that we need to think about the relationship between substance use and brain development somewhat differently,” she said.
Out of the almost 10,000 participants in the study, approximately 3500 reported trying substances by age 15 (which mostly means small encounters with more common substances like a sip of alcohol) compared to the remainder that did not.
They compared the two groups' brain scans from before trying substances in early adolescence and found several differences in brain structure between the two groups. The researchers used statistical tools to control for variables like family membership, prenatal exposure to substances, and the associations still held.
That small differences in these brain structure features precede use of substances in youth could point to a propensity towards early experimentation with substances, said Miller, who is also looking at how impulsivity overlaps with these structures.
“The patterns of associations that we're seeing are of interest,” compared to what has been seen before, he added. Next steps will include filling in the puzzle pieces in the right order to sort the origin of substance use disorders.
If you or someone you know is struggling or in crisis, help is available. Call or text 988 or chat at . To learn how to get support for mental health, drug or alcohol conditions, visit . If you are ready to locate a treatment facility or provider, you can go directly to  or call 800-662-HELP (4357).
Miller AP, Baranger DAA, Paul SE, Garavan H, Mackey S, Tapert SF, LeBlanc KH, Agrawal A, Bogdan R. Neuroanatomical variability and substance use initiation in late childhood and early adolescence. JAMA Network Open. DOI: https://doi.org/10.1001/jamanetworkopen.2024.52027
This study was supported by R01DA54750 (RB, AA). Additional funding included: APM (T32DA015035, K01AA031724), DAAB (K99AA030808), SEP (F31AA029934), AA (R01DA54750), RB (R01DA54750, R21AA027827, U01DA055367). Data for this study were provided by the Adolescent Brain Cognitive Development (ABCD) study which was funded by awards U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147 from the NIH and additional federal partners (https://abcdstudy.org/federal-partners.html). (The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.