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Stimulant medications in children with ADHD normalize the structure of brain regions associated with attention and reward

Neuropsychopharmacology (2024)Cite this article

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Abstract

Children with ADHD show abnormal brain function and structure. Neuroimaging studies found that stimulant medications may improve brain structural abnormalities in children with ADHD. However, prior studies on this topic were conducted with relatively small sample sizes and wide age ranges and showed inconsistent results. In this cross-sectional study, we employed latent class analysis and linear mixed-effects models to estimate the impact of stimulant medications using demographic, clinical measures, and brain structure in a large and diverse sample of children aged 9-11 from the Adolescent Brain and Cognitive Development Study. We studied 273 children with low ADHD symptoms and received stimulant medication (Stim Low-ADHD), 1002 children with high ADHD symptoms and received no medications (No-Med ADHD), and 5378 typically developing controls (TDC). After controlling for the covariates, compared to Stim Low-ADHD and TDC, No-Med ADHD showed lower cortical thickness in the right insula (INS, d = 0.340, PFDR = 0.003) and subcortical volume in the left nucleus accumbens (NAc, d = 0.371, PFDR = 0.003), indicating that high ADHD symptoms were associated with structural abnormalities in these brain regions. In addition, there was no difference in brain structural measures between Stim Low-ADHD and TDC children, suggesting that the stimulant effects improved both ADHD symptoms and ADHD-associated brain structural abnormalities. These findings together suggested that children with ADHD appear to have structural abnormalities in brain regions associated with saliency and reward processing, and treatment with stimulant medications not only improve the ADHD symptoms but also normalized these brain structural abnormalities.

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Fig. 1: Conditional probabilities are based on ADHD symptoms and statistics on ADHD medication in each latent class.
Fig. 2: One-way ANOVA analysis and post-hoc test.

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Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org), held in the National Institute of Mental Health (NIMH) Data Archive (NDA). The ABCD Study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147. A full list of supporters is available at https://abcdstudy.org/nih-collaborators. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/ principal-investigators.html. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the National Institutes of Health (NIH) or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from NIMH Data Archive Digital Object Identifier (https://doi.org/10.15154/1519007). This work was supported by the National Natural Science Foundation of China (grant number 82172023, 82202252, 82302292); National Key R&D Program of China (No.2022YFC3500603); the Fundamental Research Funds for the Central Universities (ZYTS23188; XJSJ23190; XJS221201; QTZX23093); Natural Science Basic Research Program of Shaanxi (grant number 2022JC-44, 2022JQ-622, 2023-JC-QN−0922, 2023-ZDLSF−07) and support in part from the Intramural Research Program of the National Institute on Alcoholism and Alcohol Abuse (grant number Y1AA3009) to P.M., D.T., N.D.V., G.J.W.

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Author notes

  1. These authors contributed equally: Feifei Wu, Wenchao Zhang.

Authors and Affiliations

  1. Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi’an, Shaanxi, 710126, China

    Feifei Wu, Wenchao Zhang, Weibin Ji, Yaqi Zhang, Fukun Jiang, Guanya Li, Yang Hu & Yi Zhang

  2. International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi’an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi’an, Shaanxi, 710126, China

    Feifei Wu, Wenchao Zhang, Weibin Ji, Yaqi Zhang, Fukun Jiang, Guanya Li, Yang Hu & Yi Zhang

  3. Kindergarten affiliated to Air Force Medical University, Xi’an, Shaanxi, 710032, China

    Xiaorong Wei

  4. College of Westa, Southwest University, Chongqing, 400715, China

    Haoyi Wang

  5. Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA

    Szu-Yung (Ariel) Wang, Peter Manza, Dardo Tomasi, Nora D. Volkow & Gene-Jack Wang

  6. Chongqing Key Laboratory of Image Cognition, Chongqing University of Posts and Telecommunications, Chongqing, 400065, China

    Xinbo Gao

  7. Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing, 400064, China

    Xinbo Gao

Authors
  1. Feifei Wu
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  2. Wenchao Zhang
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  3. Weibin Ji
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  15. Gene-Jack Wang
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  16. Yi Zhang
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Contributions

Conceptualization, Gene-Jack Wang, Yi Zhang; Data acquisition, Feifei Wu, Fukun Jiang, Weibin Ji, Yaqi Zhang, Wenchao Zhang, Szu-Yung Ariel Wang; Data analysis, Feifei Wu, Wenchao Zhang, Weibin Ji, Guanya Li, Yang Hu, Xiaorong Wei, Haoyi Wang; Writing-Original Draft, Feifei Wu, Weibin Ji, Yi Zhang, Gene-Jack Wang, Xinbo Gao; Writing-Review & Editing, Peter Manza, Dardo Tomasi, Nora D. Volkow. All authors critically reviewed the content and approved the final version for publication.

Corresponding authors

Correspondence to Gene-Jack Wang or Yi Zhang.

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Wu, F., Zhang, W., Ji, W. et al. Stimulant medications in children with ADHD normalize the structure of brain regions associated with attention and reward. Neuropsychopharmacol. (2024). https://doi.org/10.1038/s41386-024-01831-4

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