Longitudinal Mapping of Cortical Thickness and Clinical Outcome in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder
Abstract
CONTEXT: Data from a previous prospective study of lobar volumes in children with attention-deficit/hyperactivity disorder (ADHD) are reexamined using a measure of cortical thickness. OBJECTIVE: To determine whether regional differences in cortical thickness or cortical changes across time characterize ADHD and predict or reflect its clinical outcome. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal study of 163 children with ADHD (mean age at entry, 8.9 years) and 166 controls recruited mainly from a local community in Maryland. Participants were assessed with magnetic resonance imaging. Ninety-seven patients with ADHD (60%) had 2 or more images and baseline and follow-up clinical evaluations (mean follow-up, 5.7 years). MAIN OUTCOME MEASURES: Cortical thickness across the cerebrum. Patients with ADHD were divided into better and worse outcome groups on the basis of a mean split in scores on the Children's Global Assessment Scale and persistence/remission of DSM-IV-defined ADHD. RESULTS: Children with ADHD had global thinning of the cortex (mean reduction, -0.09 mm; P=.02), most prominently in the medial and superior prefrontal and precentral regions. Children with worse clinical outcome had a thinner left medial prefrontal cortex at baseline than the better outcome group (-0.38 mm; P=.003) and controls (-0.25 mm; P=.002). Cortical thickness developmental trajectories did not differ significantly between the ADHD and control groups throughout except in the right parietal cortex, where trajectories converged. This normalization of cortical thickness occurred only in the better outcome group. CONCLUSIONS: Children with ADHD show relative cortical thinning in regions important for attentional control. Children with a worse outcome have "fixed" thinning of the left medial prefrontal cortex, which may compromise the anterior attentional network and encumber clinical improvement. Right parietal cortex thickness normalization in patients with a better outcome may represent compensatory cortical change.
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Imaging studies have shown the PFC to be thinner in ADHD individuals, thereby hampering proper maturation and prefrontal connectivity leading to attentional dysfunction.
“Imaging studies have shown the PFC to be thinner in ADHD individuals, thereby hampering proper maturation and prefrontal connectivity leading to attentional dysfunction [382, 383].”
From Development of prefrontal cortex (2022) · cites this paper as [382]
Children with ADHD show abnormalities in premotor regions, in particular the supplementary motor area, on anatomic and functional imaging studies.
“Consistent with this, children with ADHD show abnormalities in premotor regions, in particular the supplementary motor area on anatomic (Mostofsky, Cooper, Kates, Denckla, & Kaufmann, 2002; Shaw et al., 2006) and functional (Suskauer, Simmonds, Fotedar et al., 2008) imaging studies.”
From Increased intra-individual reaction time variability in attention-deficit/hyperactivity disorder across response inhibition tasks with different cognitive demands (2009) · cites this paper as Shaw et al., 2006
Examination of cortical thickness in ADHD revealed significant thinning principally localized to the pre-SMA.
“examination of cortical thickness in ADHD revealed significant thinning principally localized to the pre-SMA”
From Meta-analysis of Go/No-go tasks demonstrating that fMRI activation associated with response inhibition is task-dependent (2008) · cites this paper as Shaw et al., 2006
Shaw et al. reported that children with ADHD followed a similar sequential pattern of cortical development but were delayed by as much as 2-3 years depending on the specific cortical region.
“Shaw et al. (Shaw et al., 2006; Shaw et al., 2007a; Shaw et al., 2007b) reported that children with ADHD followed a similar sequential pattern of cortical development, yet were delayed by as much as 2 – 3 years, depending upon the specific cortical region (Shaw et al., 2007a).”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Shaw et al., 2006
Shaw et al. found links between cortical thickness and clinical outcome: worse outcome had fixed thinning of the left medial PFC, and better outcomes had right parietal normalization.
“Additional research from this group (Shaw et al., 2006) found links between cortical thickness and clinical outcome such that ADHD children with worse outcome had “fixed” thinning of the left medial PFC and those with better outcomes had right parietal normalization, which was suggested to represent compensatory cortical change.”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Shaw et al., 2006
This hypothesis is consistent with data suggesting that trajectories of cortical development throughout middle childhood might be closely linked to ADHD outcomes, and that lower reaction time variability is associated with increased activation of the prefrontal circuit in children with ADHD.
“This hypothesis is consistent with data suggesting that trajectories of cortical development throughout middle childhood might be closely linked to ADHD outcomes (Shaw et al., 2006; Shaw et al., 2007b), and that lower reaction time variability is associated with increased activation of the prefrontal circuit (prefrontal cortex and caudate) in children with ADHD (Suskauer et al., 2008).”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Shaw et al., 2006
Both environmental (history of stimulant medication treatment) and genetic (dopamine D4 receptor genotype) factors affected the developmental trajectory of cortical thickness.
“Both environmental (history of treatment with stimulant medication) and genetic (genotype of the dopamine (DA) receptor D4 gene) factors affected the developmental trajectory.”
From Understanding the Effects of Stimulant Medications on Cognition in Individuals with Attention-Deficit Hyperactivity Disorder: A Decade of Progress (2011) · cites this paper as Shaw et al (2006)
NIMH longitudinal brain imaging provided evidence of a global reduction in brain volume and multiple regional differences in brain anatomy, suggesting approximately 10% reduction in prefrontal, basal ganglia, corpus callosum, and cerebellum.
“A program of longitudinal brain imaging was established in the child psychiatry branch of the National Institute of Mental Health (NIMH), and the ADHD component of this program has provided evidence of a global reduction in brain volume, as well as multiple regional differences in brain anatomy, suggesting an approximately 10% reduction in prefrontal, basal ganglia, corpus callosum, and cerebellum”
From Understanding the Effects of Stimulant Medications on Cognition in Individuals with Attention-Deficit Hyperactivity Disorder: A Decade of Progress (2011) · cites this paper as Shaw et al, 2006
Shaw et al. (2006, 2007) reported that cortical thickness was reduced in childhood in ADHD cases compared with controls.
“Shaw et al (2006) and Shaw et al (2007) reported differences in brain development based on measures of cortical thickness, which was reduced in childhood in ADHD cases compared with controls.”
From Understanding the Effects of Stimulant Medications on Cognition in Individuals with Attention-Deficit Hyperactivity Disorder: A Decade of Progress (2011) · cites this paper as Shaw et al (2006)
8-year-old children with ADHD and histories of institutional rearing had widespread cortical thinning similar to what has been described in children with ADHD without histories of deprivation.
“Using structural imaging, recent data from BEIP (McLaughlin et al, 2013) demonstrated that 8-year-old children with ADHD and histories of institutional rearing had widespread cortical thinning similar to what has been described in children with ADHD without histories of deprivation (Narr et al, 2009;Shaw et al, 2006).”
From Deviations from the expectable environment in early childhood and emerging psychopathology (2015) · cites this paper as Shaw et al, 2006
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Self-citationADHD and Poor Motor Performance From a Family Genetic Perspective
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The case for causal influences of action videogame play upon vision and attention
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“Finally, neuroimaging data from ADHD children indicate delays throughout much of the neocortex, rather than a specific region (Shaw et al., 2006).”
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Neuroanatomical changes in a mouse model of early life neglect
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- Authors
- Shaw, P., Lerch, J., Greenstein, D., Sharp, W., Clasen, L., Evans, A., Giedd, J., Castellanos, F. X., & Rapoport, J.
- Affiliations
- National Institute of Mental Health (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2006-05-01
- Volume
- 63
- Issue
- 5
- Pages
- 540
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2103400599
- Cited by
- 703
- References
- 15
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 16 · 2023: 20 · 2022: 23 · 2021: 31 · 2020: 32 · 2019: 37 · 2018: 27 · 2017: 26 · 2016: 34 · 2015: 46 · 2014: 52 · 2013: 45 · 2012: 57
- FWCI
- 25.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (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 › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, cortical thickness, cortical thinning, medial prefrontal cortex, clinical outcomes, longitudinal brain development, right parietal cortex, children and adolescents
- MeSH terms
- Adolescent, Atrophy, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Cerebral Cortex, Child, Female, Gyrus Cinguli, Humans, Functional Laterality, Longitudinal Studies, Magnetic Resonance Imaging, Male, Parietal Lobe, Prognosis, Prospective Studies, Psychiatric Status Rating Scales, Comorbidity, Prefrontal Cortex, Diagnostic and Statistical Manual of Mental Disorders
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