Stimulant Medication Normalizes Brain Structures in Children with ADHD: New Study
Stimulant medication use may decrease symptom severity and normalize structural brain abnormalities associated with ADHD in children, according to this large but limited neuroimaging study.
December 19, 2024
Stimulant medication may normalize certain brain regions impacted by ADHD in children, according to a cross-sectional neuroimaging study of 7,126 children aged 9 to 10 recently published in Neuropsychopharmacology.1
Study participants were divided into three groups. The “no-med ADHD” group included 1,002 children with severe ADHD symptoms who were not taking stimulant medication. The “stim low-ADHD” group included 273 children whose ADHD symptoms were mild and well-managed with stimulant medication. The “TDC” group included 5,378 typically developing controls.
ADHD symptoms experienced by the no-med ADHD group were associated with brain structure abnormalities not seen in the TDC or stim low-ADHD group, including:
- lower cortical thickness in the insula (INS), a brain area associated with saliency detection or the ability to prioritize information
- less grey matter volume in the nuclear accumbens (NAc), a brain area associated with reward processing and motivation
Children in the stim low-ADHD group showed no significant differences in these brain areas compared to controls. This contrast in structural MRIs suggests that stimulant medication may work to normalize some (but not all) brain regions and improve symptoms in children with ADHD.
Stimulant medication was not associated with improvement in all brain regions. Among those not impacted were the following:
- the caudate (CAU), a brain area responsible for motor control
- the amygdala (AMY), a brain area responsible for emotions
“This result is consistent with previous studies,” the researchers wrote. “Reduced volume in children with ADHD in the CAU is one of the most replicated findings in sMRI studies. No effect of stimulant medications was found in the CAU in the participants with ADHD in several cross-sectional studies. Along the same lines, longitudinal studies on children pointed to the improvement of volumes in the CAU associated with age but not stimulant medications… and two previous studies also pointed out there was no effect of stimulant medications on the AMY.”
Non-stimulant medication did not significantly impact brain structure.
A separate validation analysis included 273 participants with high ADHD symptoms who were taking stimulant medication; the results were consistent with the main study and still suggested that stimulant medication had a positive and noticeable effect on the brain structure of children in this group compared to the no-med ADHD group, even though both groups had high symptom severity at the time of the study.
“These findings are important for the treatment of children with ADHD using stimulant medication,” the researchers wrote.
Stimulant Medication & the ADHD Brain
Stimulants are the first-line treatment for ADHD in children aged 6 and older, teens, and adults. However, some people with ADHD discontinue medication due to side effects. The most common side effects reported by caregivers in ADDitude’s 2023 treatment survey were appetite suppression, irritability or moodiness, and sleep problems.
“Our current medication treatments for ADHD work quite well, but unfortunately, many children stop the treatment or stop taking medication,” said Jonathan Posner, M.D., in his 2020 ADDitude webinar, “Secrets of the ADHD Brain: How Brain Imaging Helps Us Understand and Treat Attention Deficit.” “In fact, the majority of teenagers with ADHD will stop treatment within two years.”
Understanding the parts of the brain that are impacted by stimulant medication can help refine treatment and determine “which of those changes are responsible for symptom improvement versus side effects,” Posner said.
“One of the things that brain imaging has shown is that the development of the brain in children with ADHD seems to be somewhat delayed,” Posner said. “But the overall course of development in children with ADHD versus without ADHD is very similar. It’s almost as if the ADHD brain is a couple of years behind. The very optimistic part of this is that it ultimately does catch up for most children with ADHD.”
For the majority of patients, ADHD symptoms do continue into adulthood, and the prevalence of ADHD in adults is rising. 2, 3 However, the present study confirmed Posner’s observations and found that children with even severe ADHD caught up developmentally for the region of the brain responsible for prioritizing information.
MRI scans showed greater cortical thickness in the INS region for the stim-low ADHD group and TDC group compared to the no-med ADHD group. However, data from a two-year follow-up analysis showed these differences were no longer present. Development of the INS is complicated, the researchers noted, but they suggested that “the No-Med group has delayed INS development at baseline, which eventually catches up to the other children.” Researchers theorize that stimulant medication may speed up this process and will continue to follow up with children over the next few years.
Limitations & Future Research
Participant data was obtained from the Adolescent Brain Cognitive Development (ABCD) study, an ongoing study since 2019 that will follow children over 10 years. Data was obtained via structural MRIs and symptom questionnaires and analyzed using linear mixed-effects models (LMM). The study included measures of cortical thickness, cortical area, cortical and subcortical volumes, and total intracranial volume.
The ABCD study lacked diagnostic information for ADHD; therefore, researchers grouped participants using latent class analysis (LCA) and 18 ADHD symptoms from the K-SADS — a moderately reliable test of affective disorders and schizophrenia. Children with bipolar disorders and anxiety disorders, oppositional defiant disorder, obsessive-compulsive disorders, and conduct disorders were excluded from the study.
Results indicate that stimulant medication may enhance brain structure and alleviate ADHD symptoms; however, this study was cross-sectional and did not establish clear causation. Information on the mean dose and duration of participants’ stimulant medication use was missing from the study. Additionally, researchers warned that the study did not fully capture the association between brain structure and ADHD severity. The stim-low ADHD group was much smaller than the other two groups, which may have hindered the study’s results. The two-year follow-up (in line with ABCD study release 4.0) included fewer participants (3,992 after exclusion criteria). Results should be interpreted with caution.
Future research should further incorporate supplemental data on stimulant use, study stimulant use by patients with severe ADHD, and include more longitudinal data.
View Article Sources
1Wu, F., Zhang, W., Ji, W. et al. (2024). Stimulant medications in children with ADHD normalize the structure of brain regions associated with attention and reward. Neuropsychopharmacol, 49, 1330–1340. https://doi.org/10.1038/s41386-024-01831-4
2U.S. Centers for Disease Control and Prevention. (2024, October 4). ADHD in adults: an overview.
https://www.cdc.gov/adhd/articles/adhd-across-the-lifetime.html
3American Psychiatric Association. (2019, November 15). ADHD increasing among adults.
https://www.psychiatry.org/news-room/apa-blogs/adhd-increasing-among-adults