New Research Challenges Views on Substance Use Disorders, Linking Brain Structure to Substance Initiation

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 Art & Sciences and the School of Medicine studied the brain scans of nearly 10,000 children in the large-scale Adolescent Brain Cognitive Development 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, ​the Dean’s Distinguished Professor of Psychological & Brain Sciences in Arts & Sciences and co-author of this research, published Dec. 30 in JAMA Network Open.

In the research, Bogdan, along with first author Alex Miller, 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; other pieces include the genetic building blocks that factor into brain structure from the get-go and early home environments.

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 3,500 reported trying substances by age 15 (which mostly means small encounters with more common substances like a sip of alcohol) compared with the remainder who 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 such as family membership and prenatal exposure to substances, and the associations still held.

Those small differences in these brain structure features that precede use of substances in youth could point to a propensity toward 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 with 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.