Meta‐analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects
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Frodl T, Skokauskas N. Meta‐analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects. Objective: About 50–80% of ADHD cases have been found to persist into adulthood, but ADHD symptoms change with age. The aim of this study was to perform a meta‐analysis of MRI voxel‐based morphometry (VBM) and manual tracing studies to identify the differences between adults and children with ADHD as well as between treated and untreated individuals. Method: Several databases were searched using keywords ‘attention‐deficit and MRI’, ‘ADHD and MRI’. Gray matter volumes from VBM studies and caudate volumes from tracing studies of patients and controls were analyzed using signed differential mapping. Results: Meta‐analyses detected reduced right globus pallidus and putamen volumes in VBM studies as well as decreased caudate volumes in manual tracing studies in children with ADHD. Adult patients with ADHD showed volume reduction in the anterior cingulate cortex (ACC). A higher percentage of treated participants were associated with less changes. Conclusion: Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non‐treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure.
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In patients with ADHD, meta-analyses have documented smaller volumes across several brain regions, most consistently in the right globus pallidus, right putamen, caudate nucleus and cerebellum.
“In patients with ADHD, meta-analyses have documented smaller volumes across several brain regions, most consistently in the right globus pallidus, right putamen, caudate nucleus and cerebellum 84,85 .”
From Attention-deficit/hyperactivity disorder (2015) · cites this paper as [85]
The Discussion (p. 8) reports reduced right globus pallidus and putamen volumes in children with ADHD, and reduced caudate volumes in a separate meta-analysis of manual-tracing studies. But the discussion on p. 9 says cerebellar reductions appeared only in some studies, did not appear in this paper’s VBM meta-analysis, and were less consistent than basal-ganglia changes. The claim therefore overstates the evidence for the cerebellum and does not retain the findings’ childhood qualification. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSome brain volumetric alterations observed in childhood normalize with age, whereas other measures remain fixed.
“Some brain volumetric alterations observed in childhood normalize with age 82,85 , whereas other m easures remain fixed.”
From Attention-deficit/hyperactivity disorder (2015) · cites this paper as [85]
The Discussion (p. 8) says that basal-ganglia volume differences seen in children with ADHD seem to diminish by adulthood. It does not establish that they fully normalize with age: the studies were cross-sectional, and the limitations section (p. 10) cautions against drawing longitudinal conclusions. The citation follows the normalization clause, so the statement about other measures remaining fixed is not assessed here. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAdults with ADHD show reduced fronto-striatal and cerebellar gray matter volume overall, and these reductions appear more robust in males.
“While adults with ADHD show reduced fronto-striatal and cerebellar gray matter volume overall [127,128,129,130], these reductions appear more robust in males [131,132,133].”
From ADHD in Adulthood: Clinical Presentation, Comorbidities, and Treatment Perspectives (2025) · cites this paper as [127]
The Adults section (p. 6) reports reduced gray matter in the anterior cingulate cortex in adults with ADHD. The Results (p. 5) place the putamen and globus pallidus reductions in children, while the discussion (p. 9) says cerebellar changes did not appear in this meta-analysis. The paper also cautions that possible gender effects should not be overinterpreted (p. 8); it does not establish that these reductions are more robust in adult males. (LLM, conf=0.88)
Experimental — accuracy not yet measuredRecent meta-analyses emphasize the reduced volume of the basal ganglia, especially the lentiform nucleus (globus pallidus and putamen) and the caudate, seen in ADHD patients.
“They emphasize the reduced volume of the basal ganglia, especially the lentiform nucleus (globus pallidus and putamen) (Ellison-Wright et al. 2008; Nakao et al. 2011) and the caudate (Ellison-Wright et al. 2008; Frodl and Skokauskas 2012; Nakao et al. 2011; Valera et al. 2007) seen in ADHD patients.”
From The neurobiological link between OCD and ADHD (2014) · cites this paper as Frodl and Skokauskas 2012
Subsequent meta-analyses mainly report differences in basal ganglia together with changes in total brain or gray matter volume in ADHD.
“However, subsequent meta-analyses [8–11] mainly report differences in basal ganglia together with changes in total brain [8] or gray matter volume [11].”
From The brain anatomy of attention-deficit/hyperactivity disorder in young adults—a magnetic resonance imaging study (2017) · cites this paper as [10]
The caudate and putamen are smaller in children but not in adults with ADHD.
“which are smaller in children but not in adults with ADHD [7, 10].”
From The brain anatomy of attention-deficit/hyperactivity disorder in young adults—a magnetic resonance imaging study (2017) · cites this paper as [10]
The reduced grey matter concentrations in the left caudate head in young adults with ADHD suggest that the macrostructural abnormalities in the basal ganglia may normalize at a later stage in adults with ADHD.
“In addition, the reduced grey matter concentrations in the left caudate head in young adults with ADHD suggest that the macrostructural abnormalities in the basal ganglia may normalize at a later stage in adults with ADHD [7, 10, 24].”
From The brain anatomy of attention-deficit/hyperactivity disorder in young adults—a magnetic resonance imaging study (2017) · cites this paper as [10]
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Attention-deficit/hyperactivity disorder
Faraone, S. V., Asherson, P., Banaschewski, T., Biederman, J., Buitelaar, J. K., Ramos-Quiroga, J. A., Rohde, L. A., Sonuga-Barke, E. J. S., Tannock, R., & Franke, B. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.20 · Cited by 1,479 · see citing works
Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies
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Updated European Consensus Statement on diagnosis and treatment of adult ADHD
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Live fast, die young? A review on the developmental trajectories of ADHD across the lifespan
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Self-citationNorman, L. J., Carlisi, C., Lukito, S., Hart, H., Mataix-Cols, D., Radua, J., & Rubia, K. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.0700 · Cited by 426 · see citing works
Noreika, V., Falter, C. M., & Rubia, K. (2013) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2012.09.036 · Cited by 339 · see citing works
Rubia, K., Alegria, A. A., Cubillo, A. I., Smith, A. B., Brammer, M. J., & Radua, J. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.10.016 · Cited by 315 · see citing works
“Meta-regression analyses show that long-term stimulant medication is associated with more normal basal ganglia structure (8,78), parallel to the metaregression findings of an association with more normal striatal function during attention tasks (37).”
Neuroinflammation as a risk factor for attention deficit hyperactivity disorder
Dunn, G. A., Nigg, J. T., & Sullivan, E. L. (2019) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.05.005 · Cited by 299 · see citing works
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Bolea-Alamañac, B., Nutt, D. J., Adamou, M., Asherson, P., Bazire, S., Coghill, D., Heal, D., Müller, U., Nash, J., Santosh, P., et al. (2014) · Journal of Psychopharmacology · doi:10.1177/0269881113519509 · Cited by 287 · see citing works
de Wit, S. J., Alonso, P., Schweren, L., Mataix-Cols, D., Lochner, C., Menchón, J. M., Stein, D. J., Fouche, J.-P., Soriano-Mas, C., Sato, J. R., et al. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.13040574 · Cited by 278 · see citing works
Graham, A. M., Rasmussen, J. M., Rudolph, M. D., Heim, C. M., Gilmore, J. H., Styner, M., Potkin, S. G., Entringer, S., Wadhwa, P. D., Fair, D. A., et al. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.05.027 · Cited by 282 · see citing works
Lukito, S., Norman, L., Carlisi, C., Radua, J., Hart, H., Simonoff, E., & Rubia, K. (2020) · Psychological Medicine · doi:10.1017/s0033291720000574 · Cited by 248 · see citing works
Samea, F., Soluki, S., Nejati, V., Zarei, M., Cortese, S., Eickhoff, S. B., Tahmasian, M., & Eickhoff, C. R. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.02.011 · Cited by 245 · see citing works
Ersche, K. D., Williams, G. B., Robbins, T. W., & Bullmore, E. T. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.02.017 · Cited by 205 · see citing works
Greven, C. U., Bralten, J., Mennes, M., O’Dwyer, L., van Hulzen, K. J. E., Rommelse, N., Schweren, L. J. S., Hoekstra, P. J., Hartman, C. A., Heslenfeld, D., et al. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.3162 · Cited by 198 · see citing works
A review of attention-deficit/hyperactivity disorder from the perspective of brain networks
De La Fuente, A., Xia, S., Branch, C., & Li, X. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00192 · Cited by 159 · see citing works
Response Inhibition and Interference Control in Obsessive–Compulsive Spectrum Disorders
van Velzen, L. S., Vriend, C., de Wit, S. J., & van den Heuvel, O. A. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00419 · Cited by 159 · see citing works
Structural and functional neuroimaging in attention-deficit/hyperactivity disorder
Albajara Sáenz, A., Villemonteix, T., & Massat, I. (2019) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.14050 · Cited by 154 · see citing works
Imaging the ADHD brain: disorder-specificity, medication effects and clinical translation
Rubia, K., Alegria, A., & Brinson, H. (2014) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2014.907526 · Cited by 146 · see citing works
Brain alterations in adult ADHD: Effects of gender, treatment and comorbid depression
Onnink, A. M. H., Zwiers, M. P., Hoogman, M., Mostert, J. C., Kan, C. C., Buitelaar, J., & Franke, B. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.11.011 · Cited by 131 · see citing works
Beyond the core-deficit hypothesis in developmental disorders
Astle, D. E., & Fletcher-Watson, S. (2020) · Current Directions in Psychological Science · doi:10.1177/0963721420925518 · Cited by 132 · see citing works
Ziegler, S., Pedersen, M. L., Mowinckel, A. M., & Biele, G. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.09.002 · Cited by 110 · see citing works
Cubillo, A., Smith, A. B., Barrett, N., Giampietro, V., Brammer, M. J., Simmons, A., & Rubia, K. (2014) · Cerebral Cortex · doi:10.1093/cercor/bhs296 · Cited by 116 · see citing works
The neurobiological link between OCD and ADHD
Brem, S., Grünblatt, E., Drechsler, R., Riederer, P., & Walitza, S. (2014) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-014-0146-x · Cited by 109 · see citing works
Dougherty, C. C., Evans, D. W., Myers, S. M., Moore, G. J., & Michael, A. M. (2016) · Neuropsychology Review · doi:10.1007/s11065-015-9300-2 · Cited by 104 · see citing works
Francx, W., Oldehinkel, M., Oosterlaan, J., Heslenfeld, D., Hartman, C. A., Hoekstra, P. J., Franke, B., Beckmann, C. F., Buitelaar, J. K., & Mennes, M. (2015) · Cortex · doi:10.1016/j.cortex.2015.08.012 · Cited by 102 · see citing works
Johnston, B. A., Mwangi, B., Matthews, K., Coghill, D., Konrad, K., & Steele, J. D. (2014) · Human Brain Mapping · doi:10.1002/hbm.22542 · Cited by 101 · see citing works
Gehricke, J.-G., Kruggel, F., Thampipop, T., Alejo, S. D., Tatos, E., Fallon, J., & Muftuler, L. T. (2017) · PLOS ONE · doi:10.1371/journal.pone.0175433 · Cited by 103 · see citing works
Lim, L., Marquand, A., Cubillo, A. A., Smith, A. B., Chantiluke, K., Simmons, A., Mehta, M., & Rubia, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063660 · Cited by 101 · see citing works
Bralten, J., Franke, B., Waldman, I., Rommelse, N., Hartman, C., Asherson, P., Banaschewski, T., Ebstein, R. P., Gill, M., Miranda, A., et al. (2013) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2013.08.020 · Cited by 93 · see citing works
Brain structure in pediatric Tourette syndrome
and The Tourette Association of America Neuroimaging Consortium, Greene, D. J., Williams III, A. C., Koller, J. M., Schlaggar, B. L., & Black, K. J. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.194 · Cited by 89 · see citing works
Leménager, T., Hoffmann, S., Dieter, J., Reinhard, I., Mann, K., & Kiefer, F. (2018) · Journal of Behavioral Addictions · doi:10.1556/2006.7.2018.13 · Cited by 91 · see citing works
Onnink, A. M. H., Zwiers, M. P., Hoogman, M., Mostert, J. C., Dammers, J., Kan, C. C., Vasquez, A. A., Schene, A. H., Buitelaar, J., & Franke, B. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.04.008 · Cited by 93 · see citing works
Tamminga, H. G. H., Reneman, L., Huizenga, H. M., & Geurts, H. M. (2016) · Psychological Medicine · doi:10.1017/s0033291716000350 · Cited by 82 · see citing works
Hu, X., Du, M., Chen, L., Li, L., Zhou, M., Zhang, L., Liu, Q., Lu, L., Mreedha, K., Huang, X., et al. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.04.012 · Cited by 75 · see citing works
Bernanke, J., Luna, A., Chang, L., Bruno, E., Dworkin, J., & Posner, J. (2022) · The Lancet Psychiatry · doi:10.1016/s2215-0366(21)00505-8 · Cited by 75 · see citing works
Iannaccone, R., Hauser, T. U., Ball, J., Brandeis, D., Walitza, S., & Brem, S. (2015) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-015-0678-4 · Cited by 74 · see citing works
Bachmann, K., Lam, A. P., Sörös, P., Kanat, M., Hoxhaj, E., Matthies, S., Feige, B., Müller, H., Özyurt, J., Thiel, C. M., et al. (2018) · Behaviour Research and Therapy · doi:10.1016/j.brat.2018.05.002 · Cited by 73 · see citing works
Ambrosino, S., de Zeeuw, P., Wierenga, L. M., van Dijk, S., & Durston, S. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx182 · Cited by 67 · see citing works
Distinct brain structure and behavior related to ADHD and conduct disorder traits
Bayard, F., Nymberg Thunell, C., Abé, C., Almeida, R., Banaschewski, T., Barker, G., Bokde, A. L. W., Bromberg, U., Büchel, C., Quinlan, E. B., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-018-0202-6 · Cited by 67 · see citing works
Lu, D., He, Y., & Tan, Y. (2022) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.719425 · Cited by 66 · see citing works
Albaugh, M. D., Orr, C., Chaarani, B., Althoff, R. R., Allgaier, N., D’Alberto, N., Hudson, K., Mackey, S., Spechler, P. A., Banaschewski, T., et al. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.01.003 · Cited by 63 · see citing works
“In adults and youths, structural abnormalities have been reported in the basal ganglia (4-10), prefrontal cortex (10-12), cerebellum (5, 10, 13, 14), anterior cingulate cortex (15), and less frequently reported in the hippocampus, amygdala, and thalamus (16, 17).”
BackgroundSteullet, P., Cabungcal, J.-H., Cuénod, M., & Do, K. Q. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00244 · Cited by 49 · see citing works
Reduced subcortical volumes among preschool-age girls and boys with ADHD
Rosch, K. S., Crocetti, D., Hirabayashi, K., Denckla, M. B., Mostofsky, S. H., & Mahone, E. M. (2018) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2017.10.013 · Cited by 49 · see citing works
Groenman, A. P., Schweren, L. J. S., Dietrich, A., & Hoekstra, P. J. (2017) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2017.1301928 · Cited by 46 · see citing works
The use of actigraphy in the monitoring of methylphenidate versus placebo in ADHD: a meta-analysis
De Crescenzo, F., Armando, M., Mazzone, L., Ciliberto, M., Sciannamea, M., Figueroa, C., Janiri, L., Quested, D., & Vicari, S. (2014) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-013-0122-x · Cited by 48 · see citing works
Unique white matter microstructural patterns in ADHD presentations—a diffusion tensor imaging study
Svatkova, A., Nestrasil, I., Rudser, K., Goldenring Fine, J., Bledsoe, J., & Semrud‐Clikeman, M. (2016) · Human Brain Mapping · doi:10.1002/hbm.23243 · Cited by 44 · see citing works
“In agreement with previous research [Bonath et al, in press; Frodl and Skokauskas, 2012], our study confirmed the ACC and frontal areas to be critical hubs in both ADHD presentations, nevertheless distinct patterns of alterations in ACC-related pathways were observed in ADHD-PI and ADHD-C compared…”
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Functional imaging changes in the medial prefrontal cortex in adult ADHD
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Structural Brain Changes and Associated Symptoms of ADHD Subtypes in Children.
Mu, S., Wu, H., Zhang, J., & Chang, C. (2022) · Cerebral Cortex · doi:10.1093/cercor/bhab276 · Cited by 29 · see citing works
From neurons to brain networks, pharmacodynamics of stimulant medication for ADHD
Parlatini, V., Bellato, A., Murphy, D., & Cortese, S. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105841 · Cited by 26 · see citing works
Smaller volumes of caudate nuclei in prepubertal children with ADHD: Impact of age
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ADHD in Adulthood: Clinical Presentation, Comorbidities, and Treatment Perspectives
Bogdańska-Chomczyk, E., Majewski, M. K., & Kozłowska, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262211020 · Cited by 15 · see citing works
“While adults with ADHD show reduced fronto-striatal and cerebellar gray matter volume overall [127–130], these reductions appear more robust in males [131–133].”
The neurobehavioral mechanisms of motivational control in attention-deficit/hyperactivity disorder
Ceceli, A. O., Natsheh, J. Y., Cruz, D., & Tricomi, E. (2020) · Cortex · doi:10.1016/j.cortex.2020.02.009 · Cited by 9 · see citing works
- Authors
- Frodl, T., & Skokauskas, N.
- Affiliations
- Trinity College Dublin (IE)
- Corresponding author
- Frodl, T.
- Venue
- Acta Psychiatrica Scandinavica
- Publisher
- Wiley
- Published
- 2011-11-28
- Volume
- 125
- Issue
- 2
- Pages
- 114-126
- ISSN
- 0001-690X (ISSN-L)
- 1600-0447
- OpenAlex
- W1546703732
- Cited by
- 530
- References
- 74
- Citations by year
- 2026: 19 · 2025: 24 · 2024: 29 · 2023: 32 · 2022: 28 · 2021: 43 · 2020: 41 · 2019: 42 · 2018: 33 · 2017: 49 · 2016: 43 · 2015: 44 · 2014: 49 · 2013: 35 · 2012: 18
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Acta Psychiatrica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, brain structure, gray matter volume, basal ganglia, globus pallidus, putamen, caudate nucleus, anterior cingulate cortex, amygdala, voxel-based morphometry, manual tracing, children versus adults, longitudinal brain changes
- MeSH terms
- Adolescent, Adult, Amygdala, Attention Deficit Disorder with Hyperactivity, Basal Ganglia, Brain, Brain Mapping, Child, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Organ Size, Young Adult
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