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New Study Suggests Brain Structure May Predispose to Substance Use
Indianapolis, January 4, 2025 — For years, experts in addiction science have operated under the assumption that neuroanatomical changes in young people who use substances like alcohol and drugs primarily result from the effects of these substances. However, groundbreaking research published in JAMA Network Open suggests that some brain differences may exist before any substance use occurs, potentially serving as markers of predispositional risk.
The study, led by Dr. Alex P. Miller, assistant professor of psychiatry at Indiana University, highlights that individual neuroanatomy—alongside environmental and genetic factors—may influence the likelihood of developing a substance use disorder.
Challenging Established Theories
Earlier research had linked substance use to reduced gray matter volume, thinner cortices, and compromised white matter integrity. These changes were widely believed to result from substance exposure. However, longitudinal and genetic studies increasingly suggest that such changes could also be pre-existing risk factors.
To probe deeper, researchers analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study, which tracks brain and behavioral development in 9,804 children across 22 U.S. sites. At baseline (mean age: 9.9 years), extensive MRI scans were performed, providing detailed information on brain structure. Data on substance use—including alcohol, nicotine, cannabis, and other drugs—were collected through interviews conducted over three years.
Significant Brain Differences Identified
The analysis revealed that 35% of participants initiated substance use before age 15, with alcohol being the most common first substance. Compared to those who refrained, those who used substances exhibited larger global brain volumes, including whole brain, cortical, and subcortical volumes.
Notably, these structural differences included region-specific variations. For example:
- Thinner cortices were observed in the frontal regions of substance users, while other lobes exhibited thicker cortices.
- Alcohol initiation correlated with additional brain changes, including greater left lateral occipital volume and thicker para-hippocampal gyri.
- Nicotine use was associated with structural changes in the superior frontal gyrus and lateral orbitofrontal cortex.
- Cannabis use was linked to differences in precentral and parietal gyrus volumes.
Crucially, most associations between brain structure and substance use initiation were detectable before substance use began, challenging the notion that these changes are primarily neurotoxic effects of substances.
Implications for Addiction Models
“These findings challenge the predominant view that brain changes in substance users result largely from exposure and suggest that neuroanatomical variability may partially reflect predispositional risk,” said Dr. Miller.
The study underscores the complexity of addiction, suggesting that environmental, genetic, and neuroanatomical factors interplay in shaping substance use risk.
Expert Perspectives
In an accompanying editorial, researchers from the University of Minnesota emphasized the need to reevaluate addiction models. “Neurotoxic effects of substances are central to current brain disease models of addiction, but these findings suggest the mechanisms may be more complex,” wrote Felix Pichardo, MA, and Dr. Sylia Wilson.
They praised the ABCD Study for its longitudinal design, which allowed researchers to establish temporal relationships between brain structure and substance use. Additionally, the inclusion of genetic components, such as twin subsamples and DNA collection, enhances the study’s ability to explore causal mechanisms.
Shaping the Future of Addiction Research
Dr. Miller expressed optimism that integrating neuroanatomical, genetic, and environmental data could transform how addiction is understood and treated. “These insights could inform more accurate models of addiction, ultimately leading to better prevention and intervention strategies,” he said.
Funded by the National Institutes of Health, this study represents a significant step forward in understanding the bidirectional relationship between brain development and substance use. As researchers continue to unravel the intricate dynamics at play, the hope is that these findings will pave the way for a deeper, more nuanced understanding of addiction.
