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Quantitative Brain Magnetic Resonance Imaging in Attention-Deficit Hyperactivity Disorder
Abstract
BACKGROUND: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. METHODS: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were .82 or greater for all MRI measures. RESULTS: Subjects with ADHD had a 4.7% smaller total cerebral volume (P = .02). Analysis of covariance for total cerebral volume demonstrated a significant loss of normal right > left asymmetry in the caudate (P = .006), smaller right globus pallidus (P = .005), smaller right anterior frontal region (P = .02), smaller cerebellum (P = .05), and reversal of normal lateral ventricular asymmetry (P = .03) in the ADHD group. The normal age-related decrease in caudate volume was not seen, and increases in lateral ventricular volumes were significantly diminished in ADHD. CONCLUSION: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.
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“several (Berquin et al., 1998; Castellanos et al., 1996; Castellanos, 2001; Castellanos et al., 2002a; Hill et al., 2003), but not all (Durston et al., 2004; Filipek et al., 1997; Hynd et al., 1990; Mostofsky et al., 2002), studies report reduced whole brain size in children with ADHD.”
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 Castellanos et al., 1996
In the citing paper
“Studies have noted reduced volume in several parts of the cerebellum in ADHD (Castellanos et al., 2002a; Castellanos et al., 1996; Durston et al., 2004; Posner & Petersen, 1990) as well as posterior cortical anomalies (Durston et al., 2004; Filipek et al., 1997; Sowell et al., 2003).”
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 Castellanos et al., 1996
In the citing paper
“Numerous structural MRI studies have reported smaller regions in the prefrontal cortex (PFC) of youth with ADHD (Castellanos et al., 1996; Castellanos et al., 2002a; Durston et al., 2004; Filipek et al., 1997; Hynd, Semrud-Clikeman, Lorys, Novey, & Eliopulos, 1990; Kates et al., 2002; Mostofsky, Cooper, Kates, Denckla, & Kaufmann, 2002; Sowell et al., 2003).”
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 Castellanos et al., 1996
In the citing paper
“Earlier mental disorder onset shapes brain development (e.g., (123)) and relates to self-injurious behaviors (1).”
From Neural correlates associated with suicide and nonsuicidal self-injury in youth (2021) · cites this paper as [123]
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“For example, MRI studies of ADHD have revealed abnormalities in the size and symmetry of the basal ganglia ~Castellanos et al., 1996; Castellanos, Giedd, Eckburg, Marsh, King, Hamburger, & Rapoport, 1994! and recent functional MRI studies show decreased activity in prefrontal cortex and basal…”
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Self-citationCortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder
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Attention-deficit hyperactivity disorder and hyperkinetic disorder
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“Reduced right globus pallidus volumes in patients with ADHD compared with age- and gender-matched control subjects are in line with two of three volumetric MRI studies that manually assessed the globus pallidus and found reduced volumes in children with ADHD compared with healthy children (21, 22), whereas a study of…”
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“More specifically, the prefrontal cortex (PFC) has been shown to be significantly smaller in ADHD children than controls (Castellanos et al., 1996; Durston et al., 2004; Filipek et al., 1997; Kates et al., 2002; Mostofsky et al., 2002) and in their unaffected siblings (Durston et al.”
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“studies, as the overall and regional brain volumes for this control group are consistent with previously published normative brain volumes for children of similar age (Castellanos et al., 1996; Reiss et al., 1996; Giedd et al., 1999; Courchesne et al., 2001).”
ResultStimulants: Therapeutic Actions in ADHD
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“Numerous structural imaging studies have shown reduced size of the prefrontal cortex in ADHD patients, particularly in the right hemisphere (”
BackgroundFrontostriatal Microstructure Modulates Efficient Recruitment of Cognitive Control
Liston, C., Watts, R., Tottenham, N., Davidson, M. C., Niogi, S., Ulug, A. M., & Casey, B. J. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhj003 · Cited by 477
“This result adds to a growing body of evidence (Lim et al., 1999; Fredericksen et al., 2002; Ardekani et al., 2003) suggesting that genetic studies of disorders like ADHD and schizophrenia, which traditionally have focused on genes regulating dopaminergic neurotransmission, should also examine the regulation of myelin…”
BackgroundNeurobehavioral mechanisms of impulsivity: fronto-striatal systems and functional neurochemistry
Dalley, J. W., Mar, A. C., Economidou, D., & Robbins, T. W. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.12.021 · Cited by 467
Neuropsychological functioning in people with ADHD across the lifespan
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“Castellanos et al. (1996) found that Full Scale IQ score correlated significantly with total brain volume and with left and right prefrontal regions.”
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Nunez, P. L. (2000) · Behavioral and Brain Sciences · doi:10.1017/s0140525x00003253 · Cited by 474
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Network homogeneity reveals decreased integrity of default-mode network in ADHD
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Self-citationPrevalence and Assessment of Attention-Deficit/Hyperactivity Disorder in Primary Care Settings
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Quantitative Brain Magnetic Resonance Imaging in Girls With Attention-Deficit/Hyperactivity Disorder
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“Studying girls with ADHD raises questions regarding severity and diagnostic va- lidity, 15,16 which we addressed by recruiting girls with ADHD in whom severity and phenomenologic characteristics were comparable with those of our previously studied boys with ADHD.”
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Treatment of Attention-Deficit–Hyperactivity Disorder
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DIAMOND, A. (2005) · Development and Psychopathology · doi:10.1017/s0954579405050388 · Cited by 428
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“Alteration in the frontal-striatal circuitry underlies the psychopathology of ADHD and probably causes the related deficits of higher cognitive functions in these individuals (Berquin et al., 1998; Castellanos et al., 1996).”
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Anatomical MRI of the developing human brain: what have we learned?
DURSTON, S., HULSHOFF POL, H. E., CASEY, B. J., GIEDD, J. N., BUITELAAR, J. K., & VAN ENGELAND, H. (2001) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200109000-00009 · Cited by 410
“ple, Castellanos et al. (1996) demonstrated a loss of”
BackgroundResultInfluentialMR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders
Geuze, E., Vermetten, E., & Bremner, J. D. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001579 · Cited by 412
Bone lead levels in adjudicated delinquents
Needleman, H. L., McFarland, C. E., Ness, R. B., Fienberg, S. E., & Tobin, M. J. (2002) · Neurotoxicology and Teratology · doi:10.1016/s0892-0362(02)00269-6 · Cited by 405
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“Consistent with these results are MRI morphometry data in ADHD children, suggesting reduced white matter volumes in the right frontal lobe of ADHD children (Castellanos et al 1996; Filipek et al 1997).”
BackgroundResultMethylphenidate improves response inhibition in adults with attention-deficit/hyperactivity disorder
Aron, A. R., Dowson, J. H., Sahakian, B. J., & Robbins, T. W. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00609-7 · Cited by 401
“Response inhibition deficits have been demonstrated in children with ADHD compared with healthy volunteers (see Schachar et al 1993 and Oosterlaan et al 1998 for meta-analysis), and functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) indicate brain differences at a specifically right frontal…”
BackgroundA review of the biological bases of ADHD: What have we learned from imaging studies?
Durston, S. (2003) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.10079 · Cited by 388
Toward a Pathophysiology of Attention-Deficit/Hyperactivint Disorder
Castellanos, F. X. (1997) · Clinical Pediatrics · doi:10.1177/000992289703600702 · Cited by 397
Seidman, L. J., Valera, E. M., Makris, N., Monuteaux, M. C., Boriel, D., Kelkar, K., Kennedy, D. N., Caviness, V. S., Bush, G., Aleardi, M., et al. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.04.031 · Cited by 386
Durston, S., Pol, H. E. H., Schnack, H. G., Buitelaar, J. K., Steenhuis, M. P., Minderaa, R. B., Kahn, R. S., & van engeland, H. (2004) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200403000-00016 · Cited by 376
“, 1991), as are right prefrontal volume (Castellanos et al., 1996; Filipek et al., 1997), caudate volume (Castellanos et al.”
BackgroundInfluentialDevelopment of the human corpus callosum during childhood and adolescence: A longitudinal MRI study
Giedd, J. N., Blumenthal, J. D., Jeffries, N. O., Rajapakse, J. C., Vaituzis, A. C., Liu, H., Berry, Y. C., Tobin, M., Nelson, J. E., & Castellanos, F. X. (1999) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(99)00017-2 · Cited by 376
Smaller prefrontal and premotor volumes in boys with attention-deficit/hyperactivity disorder
Mostofsky, S. H., Cooper, K. L., Kates, W. R., Denckla, M. B., & Kaufmann, W. E. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01412-9 · Cited by 379
“For instance, in one previous study in which aMRI was applied to cerebral cortical measurements in ADHD (Castellanos et al 1996), decreased volume was localized to the “right anterior frontal” region.”
BackgroundResultInfluentialAllen, G., & Courchesne, E. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.2.262 · Cited by 366
“This is a crucial implication in light of mounting evidence for cerebellar involvement in various neurologic and psychiatric conditions, including autism (15–17), attention deficit hyperactivity disorder (18), mood disorders (19), obsessive-”
BackgroundNeural development of selective attention and response inhibition
Booth, J. R., Burman, D. D., Meyer, J. R., Lei, Z., Trommer, B. L., Davenport, N. D., Li, W., Parrish, T. B., Gitelman, D. R., & Mesulam, M. M. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00404-x · Cited by 366
“Our finding of greater caudate activation in children is also consistent with other studies that reported younger children have larger caudate volumes than older children (Castellanos et al., 1996).”
ResultIntracortical inhibition during volitional inhibition of prepared action
Coxon, J. P., Stinear, C. M., & Byblow, W. D. (2006) · Journal of Neurophysiology · doi:10.1152/jn.01334.2005 · Cited by 337
Attention-Deficit/Hyperactivity Disorder and Attention Networks
Bush, G. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.120 · Cited by 358
“In addition to relatively consistent findings of decreased total cerebral volume of B3 to 5% (Castellanos , 2001; Castellanos et al, 1996, 2002; Seidman et al, 2005; Valera et al, 2007), volumetric studies have also found more specific abnormalities within defined regions of the lateral prefrontal…”
BackgroundSex differences in dopamine receptors and their relevance to ADHD
Andersen, S. L., & Teicher, M. H. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00044-5 · Cited by 353
Hippocampus and Amygdala Morphology in Attention-Deficit/Hyperactivity Disorder
Plessen, K. J., Bansal, R., Zhu, H., Whiteman, R., Amat, J., Quackenbush, G. A., Martin, L., Durkin, K., Blair, C., Royal, J., et al. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.7.795 · Cited by 347
DelBello, M. P., Zimmerman, M. E., Mills, N. P., Getz, G. E., & Strakowski, S. M. (2004) · Bipolar Disorders · doi:10.1046/j.1399-5618.2003.00087.x · Cited by 348
MRI analysis of an inherited speech and language disorder: structural brain abnormalities
Watkins, K. E., Vargha‐Khadem, F., Ashburner, J., Passingham, R. E., Connelly, A., Friston, K. J., Frackowiak, R. S. J., Mishkin, M., & Gadian, D. G. (2002) · Brain · doi:10.1093/brain/awf057 · Cited by 351
“The typical pattern of asymmetry in the caudate nuclei is for the right to be larger than the left (Castellanos et al., 1996; Frazier et al., 1996; Reiss et al., 1996).”
BackgroundPietschnig, J., Penke, L., Wicherts, J. M., Zeiler, M., & Voracek, M. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.09.017 · Cited by 316
Bellis, M. D. D., Hall, J., Boring, A. M., Frustaci, K., & Moritz, G. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01105-2 · Cited by 334
Brain imaging of attention deficit/hyperactivity disorder
GIEDD, J. N., BLUMENTHAL, J., MOLLOY, E., & CASTELLANOS, F. X. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb05772.x · Cited by 331
Booth, J. R., Burman, D. D., Meyer, J. R., Lei, Z., Trommer, B. L., Davenport, N. D., Li, W., Parrish, T. B., Gitelman, D. R., & Marsel Mesulam, M. (2005) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2004.00337.x · Cited by 333
“…children in fronto-striatal regions is consistent with structural neuroimaging research that shows ADHD subjects have smaller frontal and basal ganglia volumes (Aylward et al., 1996; Casey et al., 1997a; Castellanos et al., 1996, 2002; Filipek et al., 1997; Hynd et al., 1993; Yeo et al., 2003).”
BackgroundResultThe attentive brain: insights from developmental cognitive neuroscience
Amso, D., & Scerif, G. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn4025 · Cited by 369
Cerebellar Development and Clinical Outcome in Attention Deficit Hyperactivity Disorder
Mackie, S. E., Shaw, P., Lenroot, R., Pierson, R. K., GREENSTEIN, D. K., Nugent, T. F., Sharp, W. S., Giedd, J. N., & Rapoport, J. L. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.4.647 · Cited by 338
Cerebellar development and clinical outcome in attention deficit hyperactivity disorder
Mackie, S., Shaw, P., Lenroot, R., Pierson, R., Greenstein, D. K., Nugent, T. F., Sharp, W. S., Giedd, J. N., & Rapoport, J. L. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.164.4.647 · Cited by 333
The role of prenatal stress in the etiology of developmental behavioural disorders
Kofman, O. (2002) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(02)00015-5 · Cited by 337
“[18] Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, Vaituzis AC, Dickstein DP, Sarfatti SE, Vauss YC, Snelll JW, Lange N, Kaysen D, Krain AL, Ritchie GF, Rajapakse JC, Rapoport JL.”
BackgroundMunoz, D. P., Armstrong, I. T., Hampton, K. A., & Moore, K. D. (2003) · Journal of Neurophysiology · doi:10.1152/jn.00192.2003 · Cited by 345
“Third, anatomical neuroimaging studies have revealed altered architecture in the frontal lobes, caudate nucleus, and rostrum of the corpus callosum (Castellanos et al. 1996a, 2001; Giedd et al. 1994; Rubia et al. 1999).”
BackgroundErnst, M., Zametkin, A. J., Matochik, J. A., Jons, P. H., & Cohen, R. M. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-15-05901.1998 · Cited by 320
“In addition, abnormal laterality and function have been reported in dopaminergic structures by MRI (Caparulo et al., 1981; Hynd et al., 1993; Aylward et al., 1996; Castellanos et al., 1996) and SPECT/PET (single-photon emission computed tomography/positron emission tomography), respectively (Lou et al.”
BackgroundFerguson, J. H. (2000) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200002000-00018 · Cited by 321
Evaluation of Cerebellar Size in Attention-Deficit Hyperactivity Disorder
Mostofsky, S. H., Reiss, A. L., Lockhart, P., & Denckla, M. B. (1998) · Journal of Child Neurology · doi:10.1177/088307389801300904 · Cited by 311
Evidence for a pure time perception deficit in children with ADHD
Smith, A., Taylor, E., Warner Rogers, J., Newman, S., & Rubia, K. (2002) · Journal of Child Psychology and Psychiatry · doi:10.1111/1469-7610.00043 · Cited by 307
“These two regions have been found to be underactivated during a time estimation task in adolescents with ADHD (Rubia et al., 1999a, 2000, 2001) and form part of grey matter areas that have been found to be morphologically reduced in patients with ADHD (Castellanos et al., 1996).”
BackgroundArnsten, A. F. T., Scahill, L. D., & Findling, R. L. (2007) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2006.0098 · Cited by 314
“Numerous structural imaging studies have shown reduced size of the PFC in ADHD patients, particularly in the right hemisphere (Castellanos et al., 1996; Casey et al., 1997; Filipek et al., 1997; Giedd et al., 2001; Kates et al., 2002; Hill et al., 2003; Sow-ell et al., 2003).”
The Nature and Heritability of Attention-Deficit/Hyperactivity Disorder
Faraone, S. V., & Doyle, A. E. (2001) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/s1056-4993(18)30059-2 · Cited by 304
Temporal information processing in ADHD: Findings to date and new methods
Toplak, M. E., Dockstader, C., & Tannock, R. (2006) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2005.09.018 · Cited by 300
“…are the recent findings from neuroimaging studies of ADHD of structural anomalies in the cerebellum and basal ganglia (e.g., Berquin et al., 1998; Castellanos et al., 1996, 2001; Giedd et al., management, inability tasks, and present actions While cognitive modularity ( this may 2001; Mostofsky…”
Executive Function Profile of Children With Attention Deficit Hyperactivity Disorder
Shallice, T., Marzocchi, G. M., Coser, S., Savio, M., Meuter, R. F. I., & Rumiati, R. I. (2002) · Developmental Neuropsychology · doi:10.1207/s15326942dn2101_3 · Cited by 310
“Moreover, the limited investigations of direct measures of brain states and activity that have been carried out in ADHD broadly support these positions (Casey et al., 1997; Castellanos et al., 1996).”
Background
Metadata
- Authors
- Castellanos, F. X.
- Affiliations
- National Institute of Mental Health (US)
- Corresponding author
- Castellanos, F. Xavier
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 1996-07-01
- Volume
- 53
- Issue
- 7
- Pages
- 607
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2097559385
- Cited by
- 1,183
- References
- 102
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 4 · 2023: 14 · 2022: 11 · 2021: 11 · 2020: 20 · 2019: 21 · 2018: 18 · 2017: 19 · 2016: 31 · 2015: 37 · 2014: 40 · 2013: 39 · 2012: 52
- FWCI
- 25.66
- 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, brain volumetry, brain volume, caudate nucleus, globus pallidus, cerebellum, corpus callosum, lateral ventricle, hemispheric lateralization, basal ganglia, children, brain structure
- MeSH terms
- Adolescent, Age Factors, Attention Deficit Disorder with Hyperactivity, Basal Ganglia, Body Height, Body Weight, Brain, Caudate Nucleus, Cerebellum, Cerebral Ventricles, Child, Child, Preschool, Frontal Lobe, Globus Pallidus, Humans, Intelligence Tests, Functional Laterality, Magnetic Resonance Imaging, Male, Discriminant Analysis, Prefrontal Cortex
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