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Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation
Open accessAbstract
There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development. Using computational neuroanatomic techniques, we estimated cortical thickness at >40,000 cerebral points from 824 magnetic resonance scans acquired prospectively on 223 children with ADHD and 223 typically developing controls. With this sample size, we could define the growth trajectory of each cortical point, delineating a phase of childhood increase followed by adolescent decrease in cortical thickness (a quadratic growth model). From these trajectories, the age of attaining peak cortical thickness was derived and used as an index of cortical maturation. We found maturation to progress in a similar manner regionally in both children with and without ADHD, with primary sensory areas attaining peak cortical thickness before polymodal, high-order association areas. However, there was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum: the median age by which 50% of the cortical points attained peak thickness for this group was 10.5 years (SE 0.01), which was significantly later than the median age of 7.5 years (SE 0.02) for typically developing controls (log rank test χ( 1 ) 2 = 5,609, P < 1.0 × 10 −20 ). The delay was most prominent in prefrontal regions important for control of cognitive processes including attention and motor planning. Neuroanatomic documentation of a delay in regional cortical maturation in ADHD has not been previously reported.
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“Slower maturation or decreased size of the PFC and also diminished PFC, caudate or cerebellum activation have been found in patients with ADHD [77, 78].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [78]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“ADHD is associated with slowed (Shaw et al., 2007) or impaired (Shaw et al., 2009) development of the right lateral PFC, the PFC region needed for inhibiting inappropriate actions and attention to distractors (Aron, Robbins, & Poldrack, 2004).”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Shaw et al., 2007
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“ADHD is also associated with delayed maturation of the cerebral cortex.”
From Attention-deficit/hyperactivity disorder (2015) · cites this paper as [88]
The cited source says what the claim attributes to it.
In the citing paper
“In one study, the age of attaining peak cortical thickness was 10.5years for patients with ADHD and 7.5years for unaffected individuals; this delay was most prominent in the prefrontal regions that are important for executive functioning, attention and motor planning 88 .”
From Attention-deficit/hyperactivity disorder (2015) · cites this paper as [88]
The cited source says what the claim attributes to it.
In the citing paper
“While this delay (e.g., in reaching peak cortical thickness) is prominent in children [73], findings in adults are more heterogeneous.”
From ADHD in Adulthood: Clinical Presentation, Comorbidities, and Treatment Perspectives (2025) · cites this paper as [73]
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In the citing paper
“There is evidence of delayed maturation of the PFC in children with ADHD (Shaw et al., 2007).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Shaw et al., 2007
In the citing paper
“In a longitudinal study of cerebral cortex thickness, psychostimulant treatment normalized the ADHD-associated excess cortical thinning during adolescence (Shaw et al., 2007, Shaw et al., 2009, van der Marel et al., 2014).”
From Sensitive periods of substance abuse: Early risk for the transition to dependence (2017) · cites this paper as Shaw et al., 2007
In the citing paper
“Regarding age, it has been shown that patients with ADHD show a regional delay in the maturation of cortical thickness, especially in regions responsible for cognitive control such as attention, working memory, inhibition and evaluation of reward contingencies in the prefrontal cortex (Shaw et al. 2007), and a slightly earlier maturation of the primary motor cortex.”
From The neurobiological link between OCD and ADHD (2014) · cites this paper as Shaw et al. 2007
In the citing paper
“The authors thus suggested that the abnormal development of cognitive control and motor areas may drive the poor control of motor activity (Shaw et al. 2007).”
From The neurobiological link between OCD and ADHD (2014) · cites this paper as Shaw et al. 2007
In the citing paper
“its structural characteristics have been found to be related to self-regulation in a number of neurodevelopmental conditions (9–13, 32, 50, 51).”
From Multimodal imaging of the self-regulating developing brain (2012) · cites this paper as [10]
In the citing paper
“structural differences in prefrontal and cingulate cortices have repeatedly been identified in children with a range of different psychopathological conditions related to self-regulation and attention, including Attention Deficit Hyperactivity Disorder, conduct disorder, and prenatal substance exposure (10–13, 29–34).”
From Multimodal imaging of the self-regulating developing brain (2012) · cites this paper as [10]
In the citing paper
“The differential increases for children with ADHD may be a byproduct of their underdeveloped cortical structures that support working memory (Shaw et al., 2007).”
From Are Episodic Buffer Processes Intact in ADHD? Experimental Evidence and Linkage with Hyperactive Behavior (2018) · cites this paper as Shaw et al., 2007
In the citing paper
“as well as evidence of ADHD-related underdevelopment/hypoactivation (Shaw et al., 2007; Smith et al., 2006) in right frontal/prefrontal and temporoparietal regions thought to support cross-modality binding in adults (Prabhakaran et al., 2000; Zhang et al., 2004).”
From Are Episodic Buffer Processes Intact in ADHD? Experimental Evidence and Linkage with Hyperactive Behavior (2018) · cites this paper as Shaw et al., 2007
In the citing paper
“Longitudinal fMRI evidence, however, reveals a 3–5 year delay in the development of these same prefrontal/frontal regions in children with ADHD relative to typically developing children (Shaw et al., 2007).”
From Improving Outcomes for Youth with ADHD: A Conceptual Framework for Combined Neurocognitive and Skill-Based Treatment Approaches (2014) · cites this paper as Shaw et al., 2007
In the citing paper
“longitudinal fMRI investigations reveal a 3–5 year delay in the maturation of prefrontal cortical regions associated with central executive working memory functioning (Shaw et al., 2007).”
From Improving Outcomes for Youth with ADHD: A Conceptual Framework for Combined Neurocognitive and Skill-Based Treatment Approaches (2014) · cites this paper as Shaw et al., 2007
In the citing paper
“For example, delayed peaks in cortical thickness in Attention-Deficit/Hyperactivity Disorder (ADHD) (64), a disorder associated with visuospatial WM impairments (65), lead to increased cortical thickness in ADHD during late childhood and early adolescence.”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [64]
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Metadata
- Authors
- Shaw, P., Eckstrand, K., Sharp, W., Blumenthal, J., Lerch, J. P., Greenstein, D., Clasen, L., Evans, A., Giedd, J., & Rapoport, J. L.
- Affiliations
- National Institutes of Health (US)
- Montreal Neurological Institute and Hospital (CA)
- Corresponding author
- Shaw, P.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-12-04
- Volume
- 104
- Issue
- 49
- Pages
- 19649-19654
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2148343
- OpenAlex
- W2156645869
- Cited by
- 1,819
- References
- 63
- Citations by year
- 2026: 90 · 2025: 89 · 2024: 97 · 2023: 83 · 2022: 89 · 2021: 93 · 2020: 101 · 2019: 115 · 2018: 73 · 2017: 134 · 2016: 114 · 2015: 107 · 2014: 112 · 2013: 100 · 2012: 111
- FWCI
- 41.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- 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 › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, cortical maturation, cortical thickness, brain development, prefrontal cortex
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Cerebral Cortex, Child, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male
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