Neuroanatomical Variability and Early Substance Use Initiation: Insights from the ABCD Study

Adolescence is a period of rapid brain development, making it a sensitive window for experiences that may shape long-term outcomes. A new study from the Adolescent Brain Cognitive Development (ABCD) project examined whether neuroanatomical variability is linked to early initiation of alcohol, nicotine, or cannabis. Drawing on baseline brain images taken before substance use began, the researchers found regionally specific differences in cortical thickness and surface area among early initiators. The findings highlight the complexity of adolescent neurodevelopment and point to the value of large-scale, longitudinal studies in clarifying how brain structure and behaviour unfold together.

Introduction

Adolescence is a period of significant brain development, marked by structural changes that support cognitive, emotional, and behavioural growth (Casey et al., 2008; King et al., 2020; Tamnes et al., 2017). During this window, the brain is especially sensitive to environmental and behavioural influences, including the initiation of substance use. While previous studies have linked alcohol and other drug use to structural alterations in the brain, many relied on small samples or cross-sectional designs, making it difficult to disentangle whether brain variability precedes or follows substance use initiation.

The authors compared brain structure in young people who had initiated substance use with those who had not, seeking to clarify how neuroanatomical variability relates to early patterns of use. Importantly, in the subgroup of participants who were substance-naive at baseline, the researchers used neuroimaging collected before any use had begun, allowing them to examine whether brain variability was already present prior to initiation. The results indicate that regional patterns of cortical thickness and surface area could be associated with whether, and at what age, adolescents start using.

“Brain structure in early adolescence may be associated with the likelihood of initiating substance use.”

Study Design and Sample

The study leveraged baseline neuroimaging and longitudinal follow-up data from the ABCD Study, one of the largest ongoing studies of adolescent brain development in the United States (Casey et al., 2018).

A total of 11 875 children were recruited from 22 US research sites. All participants were between 9 and 10 years old at baseline, with follow-up assessments capturing information on substance use initiation. Neuroimaging data included measures of cortical thickness and surface area across brain regions, providing a detailed view of neuroanatomical variability.

Substance use was defined broadly to include any initiation of alcohol, nicotine, or cannabis. This definition enabled the researchers to distinguish early initiators from peers who had not yet engaged in these behaviours. The study’s large sample size and prospective design provided stronger power to detect links between brain structure and use, while reducing the biases that often affect smaller, retrospective studies.

Key Findings

The analysis revealed regionally specific associations between cortical thickness and substance use initiation. Adolescents who reported initiating substance use had thinner cortical mantles in the prefrontal cortex but thicker cortices in temporal, occipital, and parietal regions compared to non-initiators (Miller et al., 2024). These findings underscore that the relationship between cortical structure and substance use is not uniform across the brain, but instead follows distinct regional patterns.

Similarly, analyses of cortical surface area revealed differences that may reflect developmental variability. These associations were modest in size, as expected in a large and heterogeneous sample, but consistent with prior work suggesting that neuroanatomical variation may be linked to behavioural risk factors during adolescence (Tamnes et al., 2017).

“The cortical mantle was thinner in the prefrontal cortex, but thicker in temporal, occipital, and parietal regions among youth who initiated substance use.”

Interpretation of Results

These region-specific patterns open up avenues for understanding how differences in neurodevelopment may relate to early use. The prefrontal cortex, which is among the last regions to mature during adolescence, has been linked to behavioural regulation, decision-making, and risk-taking (Casey et al., 2008; King et al., 2020). Although the study does not establish causality, the observation that early initiators had thinner prefrontal cortices may reflect developmental differences that coincide with a higher likelihood of engaging in these behaviours.

Conversely, thicker cortices in posterior brain regions may represent alternative trajectories of maturation, as cortical thickness generally decreases with age during adolescence (Tamnes et al., 2017). These findings highlight the complexity of adolescent brain development and suggest that early substance use initiation is associated with a pattern of neuroanatomical variability rather than a single marker.

Research Implications

This study contributes to a growing body of evidence emphasising the importance of longitudinal, large-scale approaches to understanding adolescent brain development. By examining a diverse and representative cohort, Miller et al. (2024) move beyond the limitations of small samples and cross-sectional designs, providing more reliable estimates of how brain structure relates to early behavioural outcomes.

The findings suggest that neuroanatomical variability is unlikely to act as a straightforward predictor of risk. Instead, it may reflect a complex interplay between developmental processes and environmental influences. Large-scale longitudinal efforts such as the ABCD Study will be crucial to evaluate how brain development and substance use unfold together, making it possible to assess co-occurring trajectories of neuroanatomy and substance involvement over time.

“Neuroanatomical differences associated with substance use initiation may reflect complex developmental trajectories rather than static risk markers.”

Conclusion

The ABCD Study findings underscore the need for cautious interpretation of associations between brain structure and substance use in youth. While early initiators demonstrated distinct regional patterns of cortical thickness and surface area, the meaning of these differences remains to be fully understood.

Future research that follows brain development alongside substance use into young adulthood may help determine whether the differences seen in early users are a cause, a consequence, or both. For now, this study highlights the value of large-scale, long-term research in revealing how the developing brain and behaviour are intertwined.

Where next?

In this session, led by Dr. Sharon Levy who will explore the neurodevelopmental foundations of adolescent substance use, showing how brain development helps explain why experimentation during this period can lead to serious risk. From legal substances like alcohol and nicotine to medications and illicit drugs such as opioids and fentanyl, their effects on the adolescent brain can be both immediate and long lasting. Essential for professionals working with young people, this session offers a compelling look at the science behind substance use and the importance of early, informed intervention.

Use the interactive programme below to gain an overview of the topic, meet the speaker, test your knowledge, and a whole lot more!