Drug-using teens show distinct patterns of brain development tied to dopamine regulation

A new study published in Developmental Cognitive Neuroscience provides initial evidence that differences in brain chemistry during adolescence may help explain why some teens are more likely to experiment with drugs or alcohol—and why others appear to require stronger incentives to maintain cognitive focus. The findings suggest that slower developmental increases in a brain chemistry marker linked to dopamine functioning may be associated with both substance use and a greater dependence on rewards to perform well on cognitive tasks.

Adolescence is a period marked by novelty-seeking, heightened sensitivity to rewards, and risk-taking behaviors—including substance use. About 60% of teens will try alcohol, tobacco, or other drugs before adulthood, and those who begin during adolescence face a greater risk of developing a substance use disorder later in life.

Previous research has connected long-term substance use to changes in dopamine-related brain activity. For example, adults with substance use disorders tend to show lower availability of dopamine receptors and transporters in a brain region called the basal ganglia, which is involved in reward processing and cognitive control. However, much less is known about whether early changes in dopamine-linked neurodevelopment could help explain why some adolescents begin using substances in the first place.

Directly measuring dopamine in the brain is difficult, especially in younger participants. But scientists have identified a promising proxy: brain tissue iron. Iron is essential for dopamine synthesis and storage, and it tends to accumulate in dopamine-rich areas of the brain during adolescence. In this study, the researchers used magnetic resonance imaging to track tissue iron in the basal ganglia over time as a way to indirectly assess changes in dopamine-related brain development.

“We were interested in applying a new method for estimating functioning within a key neurotransmitter system. This functioning is typically difficult to measure in younger participants, but is thought to be critical for answering important questions about the propensity for early substance use,” explained Jessica S. Flannery, an assistant professor at the University of Georgia.

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The research team followed 168 adolescents from sixth through eleventh grade, collecting brain scans at up to four timepoints between the ages of roughly 12 and 18. In total, they gathered 469 functional MRI sessions from participants in a socioeconomically and ethnically diverse community in the southeastern United States. Each year, participants self-reported their substance use and completed cognitive tasks while undergoing brain scans.

At the final timepoint, a subset of 76 participants also completed an incentive-boosted Go/No-Go task called the “Planets Task.” This task assessed cognitive control by asking participants to either press a button in response to certain visual stimuli or withhold a response to others. Performance was measured under three different reward conditions: no monetary reward, a small reward, and a large reward. This design allowed the researchers to examine how performance changed based on the incentive level.

To estimate brain iron, the researchers analyzed T2*-weighted MRI signals from four subregions of the basal ganglia: the caudate, putamen, pallidum, and nucleus accumbens. Lower T2* signal corresponds to higher iron concentration, which has been associated with more robust dopamine activity.

As expected, the researchers observed that tissue iron levels tended to increase across adolescence, consistent with normal neurodevelopment. However, adolescents who reported using substances—ranging from alcohol and marijuana to vaping or other drugs—showed a slower rate of increase in iron levels, especially in the nucleus accumbens. This region is thought to be involved in assigning motivational value to rewards and has been previously linked to substance use risk.

Teens who had never used substances showed a steeper age-related increase in nucleus accumbens iron than those who had. The difference was not explained by other demographic factors such as income, race, sex, or ADHD diagnosis. While it remains unclear whether lower iron accumulation reflects a cause or consequence of substance use, the findings align with the idea that teens with less dopamine-related activity may be more drawn to substances as a way to compensate for reduced sensitivity to natural rewards.

The study also explored how tissue iron levels were linked to performance on the incentivized cognitive control task. Although all participants improved their performance when rewards were introduced, some improved dramatically, while others showed little or no change. Teens who relied more on the incentives to boost their cognitive control—dubbed “incentive-dependent”—tended to have lower iron accumulation in the putamen, a part of the basal ganglia involved in motor control and task execution.

In contrast, teens whose performance was relatively stable across all reward conditions—“incentive-independent” individuals—showed stronger age-related increases in putamen tissue iron. These findings suggest that adolescents with lower dopamine-related activity in this region may need stronger external motivation to perform at the same level as their peers.

Interestingly, while incentive-related performance was linked to brain activity during the task, tissue iron levels were not directly associated with changes in incentive-related brain activation. This indicates that while both factors relate to motivation and behavior, they may operate through distinct processes.

The key takeaway? “Differences in how teens’ brains develop might help explain why some adolescents are more likely to engage in certain health-related behaviors than others,” Flannery told PsyPost.

Although the findings point to a possible neurodevelopmental pattern that relates to both early substance use and incentive-dependent cognitive control, the study does not prove causation. Because the researchers could not disentangle preexisting differences from the effects of substance use over time, it is still unclear whether reduced iron accumulation leads to substance use, or whether even mild early use might affect brain development.

The researchers also note that incentive-boosted cognitive control and brain activity were only measured at the final timepoint, limiting their ability to track developmental changes in task performance. In addition, while tissue iron is a useful proxy for dopamine-related physiology, it is not a direct measure of dopamine function. More research is needed to clarify how iron levels reflect changes in the broader dopamine system.

“It is important to note that this study did not directly assess brain tissue iron but instead relied on a magnetic resonance-based estimation,” Flannery added. “Further, while brain iron levels are associated with parts of the dopamine system such as dopamine transporters, receptors, and the enzymes that help produce dopamine, iron levels do not directly measure how much dopamine is available or exactly how it is functioning. Scientists are still working to understand how brain iron and dopamine activity are connected, as they reflect distinct but associated aspects of brain chemistry.”

The study, “Developmental changes in dopamine-related neurophysiology and associations with adolescent substance use and incentive-boosted cognitive control,” Jessica S. Flannery, Ashley C. Parr, Kristen A. Lindquist, and Eva H. Telzer.