NEUROBIOLOGY OF ADHD IN CHILDREN AND ADOLESCENTS: A LITERATURE BASED REVIEW
Abstract
Attention Deficit Hyperactivity Disorder (ADHD) is a chronic neurobehavioral disorder whose clinical presentation alters across development. This review examines the direct relationship between underlying neurobiological mechanisms and age-related differences in ADHD manifestations between children and adolescents. Structurally, a narrative review with a systematic approach was conducted primarily using PubMed (supplemented by Google Scholar) for literature published between 2016 and 2026. Following a rigorous screening of 182 initial records, a qualitative thematic synthesis was applied to 30 peer-reviewed articles (28 for primary analysis and 2 for supplementary context) alongside 2 manually included academic textbooks. Findings reveal that delayed brain maturation and dysfunction of dopaminergic and noradrenergic neurotransmitters, combined with reduced neural flexibility between the Default Mode Network (DMN) and Executive Control Network (ECN), underpin these age-specific variations. These mechanisms directly drive the clinical shift from overt hyperactivity and impulsivity in childhood to predominant inattention, executive dysfunction, and emotional dysregulation in adolescence. In conclusion, understanding the developmental neurobiology of ADHD is clinically paramount for improving diagnostic accuracy and designing individualized management strategies. Clinicians must move beyond static treatments and adopt age-developmentally appropriate multimodal approaches that integrate targeted pharmacology and tailored psychosocial support to enhance patients' overall quality of life.
References
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Prasaja, A., Harumi, L. and Fatmawati, R. (2021) Gambaran demografi anak Attention Deficit Hyperactivity Disorder (ADHD) di Yayasan Pembinaan Anak Cacat (YPAC) Surakarta. PROFESI (Profesional Islam): Media Publikasi Penelitian, 19(2), pp. 152–157
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Sari, K. P. and Pratama, R. (2024) ‘Neuroanatomi ADHD: Studi Literatur mengenai Keterlambatan Maturasi Korteks Prefrontal’, Jurnal Kedokteran dan Kesehatan, 18(1), pp. 12-26.
Song, J., Fogarty, K., Suk, R. and Gillen, M. (2024) ‘Behavioral and mental health problems in adolescents with ADHD: Exploring the role of family resilience’, Journal of Affective Disorders Reports, 16, p. 100755. doi: 10.1016/j.jadr.2024.100755.
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Sutcubasi, B. et al. (2020) ‘Resting-state network dysconnectivity in ADHD: A system-neuroscience-based meta-analysis’, World Journal of Biological Psychiatry, 21(9), pp. 662–672. doi: 10.1080/15622975.2020.1775889.
Vestberg, S., Gustafsson, P., Gorcenco, S. and Rasmussen, A. (2023) ‘Neurocognitive and cerebellar function in ADHD, autism and spinocerebellar ataxia’, Frontiers in Systems Neuroscience, 17. doi: 10.3389/fnsys.2023.1168666.
Volnova, A. B. et al. (2023) ‘Noradrenergic Modulation of Learned and Innate Behaviors in Dopamine Transporter Knockout Rats by Guanfacine’, Biomedicines, 11(1), p. 222. doi: 10.3390/biomedicines11010222.
Wahyuni, S., Indah, N. and Rahman, T. (2023) ‘Fungsi Eksekutif dan Perkembangan Kognitif pada Anak dengan Gangguan Neurodevelopmental’, Jurnal Pendidikan Khusus, 9(2), pp. 88-100.
Wang, Y. et al. (2024) ‘The neural and genetic underpinnings of different developmental trajectories of Attention-Deficit/Hyperactivity Symptoms in children and adolescents’, BMC Medicine, 22(1). doi: 10.1186/s12916-024-03449-1.
Wolraich, M. L. et al. (2019) ‘Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents’, Pediatrics, 144(4), pp. 1-21. doi: 10.1542/peds.2019-2528.
Yin, W. et al. (2022) ‘Altered neural flexibility in children with attention-deficit/hyperactivity disorder’, Molecular Psychiatry, 27(11), pp. 4673–4679. doi: 10.1038/s41380-022-01706-4.
Younes, O. et al. (2023) ‘Functional Brain Network Connectivity Changes in Children and Adolescents with Attention-Deficit Hyperactivity Disorder: A Resting-State Brain Functional Magnetic Resonance Imaging Study’, Journal of Advances in Medicine and Medical Research, 35(16), pp. 109–120. doi: 10.9734/jammr/2023/v35i165095.
Aster, H.-C., Waltmann, M., Busch, A., Romanos, M., Gamer, M., van Noort, B., Beck, A., Kappel, V. and Deserno, L. (2023) ‘Impaired flexible reward learning is associated with blunted reinforcement sensitivity and attenuated learning and choice signals in ventral striatum and parietal cortex of ADHD patients’, medRxiv. doi: 10.1101/2023.04.14.23288555.
Ayano, G., Demelash, S., Gizachew, Y., Tsegay, L. and Alati, R. (2023) ‘The global prevalence of attention deficit hyperactivity disorder in children and adolescents: An umbrella review of meta-analyses’, Journal of Affective Disorders, 339, pp. 560–566. doi: 10.1016/j.jad.2023.07.073.
Blomberg, R., Signoret, C., Danielsson, H., Perini, I., Rönnberg, J. and Johansson Capusan, A. (2022) ‘Aberrant resting-state connectivity of auditory, ventral attention/salience and default-mode networks in adults with attention deficit hyperactivity disorder’, Frontiers in Neuroscience, 16. doi: 10.3389/fnins.2022.972730.
De Andrade Lins, C., Silva Melo, W. A., Souza, M. I., Espósito Júnior, W., Freres, S. C., Bianchim Oliveira, M. P., Malaco, J. P., & Prates Santos, P. H. (2025). Neurobiological basis of ADHD: Implications for psychiatric practice. 1(5), 1–9. https://doi.org/10.70164/ihsr.v1i5.77
De Rossi, P., D’Aiello, B., Pretelli, I., Menghini, D., Di Vara, S. and Vicari, S. (2022) ‘Age-related clinical characteristics of children and adolescents with ADHD’, Frontiers in Psychology, 13, p. 930510. doi: 10.3389/fpsyg.2022.930510.
Giannakopoulos, G. (2021) ‘Adolescents with ADHD in the school environment: A comprehensive review of academic, social, and emotional challenges and interventions’, International Journal of Pediatrics and Child Health, 9, pp. 60–67. doi: 10.12974/2311-8687.2021.09.7.
Goodman, D. W., Cortese, S. and Faraone, S. V. (2024) ‘Why is ADHD so difficult to diagnose in older adults?’, Expert Review of Neurotherapeutics, 24(10), pp. 941–944. doi: 10.1080/14737175.2024.2385932.
Gunawan, I. and Lestari, S. (2023) ‘Analisis Manifestasi Klinis dan Profil Psikologis Anak dengan ADHD di Indonesia’, Jurnal Psikologi Perkembangan, 15(2), pp. 112-125.
Ha, S. et al. (2020) ‘Maturational delay and asymmetric information flow of brain connectivity in SHR model of ADHD revealed by topological analysis of metabolic networks’, Scientific Reports, 10(1), p. 3197. doi: 10.1038/S41598-020-59921-4.
Harris, S., Green, S. M., Kumar, M. and Urs, N. M. (2021) ‘A role for cortical dopamine in the paradoxical calming effects of psychostimulants’, bioRxiv. doi: 10.1101/2021.10.01.462763.
Hasanah, U. and Kusuma, A. W. (2023) ‘Konektivitas Jaringan Saraf pada Remaja dengan Gangguan Pemusatan Perhatian dan Hiperaktivitas (GPPH)’, Jurnal Neurosains Klinik Indonesia, 4(1), pp. 45-58.
Hilger, K. et al. (2020) ‘Neurophysiological markers of ADHD symptoms in typically-developing children’, Scientific Reports, 10(1), pp. 1–15. doi: 10.1038/S41598-020-80562-0.
Hong, S. B. and Hwang, S. (2022) ‘Resting-State Brain Variability in Youth With Attention-Deficit/Hyperactivity Disorder’, Frontiers in Psychiatry, 13. doi: 10.3389/fpsyt.2022.918700.
Katz, S. M. et al. (2024) ‘Attention-Deficit/Hyperactivity Disorder and Teen Self-Report on Health Behaviors and Social-Emotional Wellbeing: United States, July 2021–December 2022’, National Health Statistics Reports, (201), pp. 1–15. doi: 10.15620/cdc:147648.
Kliegman, R. M., St. Geme, J. W., Blum, N. J., Shah, S. S., Tasker, R. C. and Wilson, K. M. (2020) Nelson textbook of pediatrics. 21st edn. Elsevier.
Kurth, F. et al. (2022) ‘Preliminary evidence for a lower brain age in children with attention-deficit/hyperactivity disorder’, Frontiers in Psychiatry, 13. doi: 10.3389/fpsyt.2022.1019546.
Li, C., Chen, Y. and Ide, J. S. (2022) ‘Gray matter volumetric correlates of attention deficit and hyperactivity traits in emerging adolescents’, Scientific Reports, 12(1). doi: 10.1038/s41598-022-15124-7.
Li, Y. (2025) ‘A Review of the Neurobiological Mechanisms and Treatment Options of ADHD Across Different Age Groups’, Transactions on Materials, Biotechnology and Life Sciences, 8, pp. 226–230. doi: 10.62051/xyne9159.
Luo, L. et al. (2023) ‘Patterns of brain dynamic functional connectivity are linked with attention-deficit/hyperactivity disorder-related behavioral and cognitive dimensions’, Psychological Medicine, pp. 1–12. doi: 10.1017/S0033291723000089.
Putri, A. R. and Zulkarnain, M. (2024) ‘Transformasi Gejala ADHD dari Masa Kanak ke Remaja: Studi Longitudinal’, Media Kesehatan Masyarakat Indonesia, 20(1), pp. 30-42.
Prasaja, A., Harumi, L. and Fatmawati, R. (2021) Gambaran demografi anak Attention Deficit Hyperactivity Disorder (ADHD) di Yayasan Pembinaan Anak Cacat (YPAC) Surakarta. PROFESI (Profesional Islam): Media Publikasi Penelitian, 19(2), pp. 152–157
Rodrigues, A. et al. (2023) ‘Alterações anatômicas e funcionais do cérebro de pacientes com transtorno do déficit de atenção e hiperatividade’, Brazilian Journal of Implantology and Health Sciences, 5(4), pp. 27–41. doi: 10.36557/2674-8169.2023v5n4p27-41.
Sari, K. P. and Pratama, R. (2024) ‘Neuroanatomi ADHD: Studi Literatur mengenai Keterlambatan Maturasi Korteks Prefrontal’, Jurnal Kedokteran dan Kesehatan, 18(1), pp. 12-26.
Song, J., Fogarty, K., Suk, R. and Gillen, M. (2024) ‘Behavioral and mental health problems in adolescents with ADHD: Exploring the role of family resilience’, Journal of Affective Disorders Reports, 16, p. 100755. doi: 10.1016/j.jadr.2024.100755.
Stahl, S. M. (2021) Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Edisi ke-5. Cambridge: Cambridge University Press. hlm 449-460.
Stern, A. et al. (2020) ‘Associations between ADHD and emotional problems from childhood to young adulthood: A longitudinal genetically sensitive study’, Journal of Child Psychology and Psychiatry, 61(11), pp. 1188–1197. doi: 10.1111/jcpp.13233.
Sutcubasi, B. et al. (2020) ‘Resting-state network dysconnectivity in ADHD: A system-neuroscience-based meta-analysis’, World Journal of Biological Psychiatry, 21(9), pp. 662–672. doi: 10.1080/15622975.2020.1775889.
Vestberg, S., Gustafsson, P., Gorcenco, S. and Rasmussen, A. (2023) ‘Neurocognitive and cerebellar function in ADHD, autism and spinocerebellar ataxia’, Frontiers in Systems Neuroscience, 17. doi: 10.3389/fnsys.2023.1168666.
Volnova, A. B. et al. (2023) ‘Noradrenergic Modulation of Learned and Innate Behaviors in Dopamine Transporter Knockout Rats by Guanfacine’, Biomedicines, 11(1), p. 222. doi: 10.3390/biomedicines11010222.
Wahyuni, S., Indah, N. and Rahman, T. (2023) ‘Fungsi Eksekutif dan Perkembangan Kognitif pada Anak dengan Gangguan Neurodevelopmental’, Jurnal Pendidikan Khusus, 9(2), pp. 88-100.
Wang, Y. et al. (2024) ‘The neural and genetic underpinnings of different developmental trajectories of Attention-Deficit/Hyperactivity Symptoms in children and adolescents’, BMC Medicine, 22(1). doi: 10.1186/s12916-024-03449-1.
Wolraich, M. L. et al. (2019) ‘Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents’, Pediatrics, 144(4), pp. 1-21. doi: 10.1542/peds.2019-2528.
Yin, W. et al. (2022) ‘Altered neural flexibility in children with attention-deficit/hyperactivity disorder’, Molecular Psychiatry, 27(11), pp. 4673–4679. doi: 10.1038/s41380-022-01706-4.
Younes, O. et al. (2023) ‘Functional Brain Network Connectivity Changes in Children and Adolescents with Attention-Deficit Hyperactivity Disorder: A Resting-State Brain Functional Magnetic Resonance Imaging Study’, Journal of Advances in Medicine and Medical Research, 35(16), pp. 109–120. doi: 10.9734/jammr/2023/v35i165095.
Published
2026-09-30
How to Cite
SAVITRI, Komang Dewi et al.
NEUROBIOLOGY OF ADHD IN CHILDREN AND ADOLESCENTS: A LITERATURE BASED REVIEW.
Mandala Of Health, [S.l.], v. 19, n. 2, p. 100-110, sep. 2026.
ISSN 2615-6954.
Available at: <https://jos.unsoed.ac.id/index.php/mandala/article/view/20355>. Date accessed: 18 oct. 2026.
doi: https://doi.org/10.20884/1.mandala.2026.19.2.20355.
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Articles
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