J Psychiatry Neurosci 2010;35(4)
© 2010 Canadian Medical Association
Background: Magnetic resonance imaging (MRI) studies have shown decreased caudate volumes in individuals with attention deficit
hyperactivity disorder (ADHD). However, most of these studies have been carried out in male children. Very little research has been
done in adults, and the results obtained in children are difficult to extrapolate to adults. We sought to compare the volume of the caudate
of adults with ADHD with that of healthy controls; we also compared these volumes between men and women. Methods: We performed
an MRI scan on 20 adults with ADHD (10 men and 10 women) aged 25–35 years and 20 healthy controls matched by age and sex. We
used voxel-based morphometry with the DARTEL algorithm for image analyses. We used the specifically designed Friederichsen,
Almeida, Serrano, Cortes Test (FASCT) to measure the severity of ADHD; both the self-reported (FASCT-SR) and the observer
(FASCT-O) versions were used. Results: The statistical parametric map showed a smaller region with low grey matter volume and a
smaller concentration of grey matter in this region of the right caudate in ADHD patients than in health controls, both in the entire sample
and within each sex. There was a significant correlation between the volume of this region of the caudate with the number of DSM IV-TR
criteria, as well as with the total scores and most of the factors of the FASCT-SR and FASCT-O scales. A separate correlation analysis
by sex gave similar results. Limitations: The study design was cross-sectional. Conclusion: The region of the right caudate with low
grey matter volume was smaller in adults with ADHD in both sexes and was correlated with ADHD severity.
Clinical correlations of grey matter reductions in the
caudate nucleus of adults with attention deficit
Luis Guillermo Almeida Montes, MD, MSc, PhD; Josefina Ricardo-Garcell, PhD; Lázaro
Barajas De La Torre, PhD; Hugo Prado Alcántara, MD; Reyna Beatriz Martínez García, MD;
Antonio Fernández-Bouzas, PhD; David Ávila Acosta, MD
Almeida Montes, Prado Alcántara, Martínez García — Departamento de Investigación del Centro Estatal de Salud Mental,
Querétaro; Almeida Montes, Ricardo-Garcell — Departamento de Investigación del Instituto de Nerurobiología de la Universi-
dad Nacional Autónoma de México, Querétaro; Barajas De La Torre — Instituto Tecnológico y de Estudios Superiores de
Monterrey, Querétaro; Fernández-Bouzas, Avila Acosta — Departamento de Neuroradiología del Instituto de Nerurobiología
Universidad Nacional Autónoma de México, Querétaro, México
Follow-up studies have found that 5%–66% of children with
attention deficit hyperactivity disorder (ADHD) continue to
have this disorder into adulthood.1In addition, ADHD is more
frequent in boys than girls.2As of 1990, there have been many
structural magnetic resonance imaging (MRI) studies involv-
ing ADHD individuals,3-5but most research has focused on pa-
tients aged 9 to 15 years, and the majority (95%) of samples
have included only male patients. Despite the homogeneity of
the samples, there have been many contradictory findings,
likely owing to differences in experimental methods, particu-
larly those used to measure the encephalic structures.6
Valera and colleagues4a meta-analysis of the data from 21
non–voxel based morphometry (VBM) studies involving pa-
tients with ADHD.4They concluded that the regions most
frequently assessed and displaying the largest differences in
ADHD individuals included the cerebellar regions, the sple-
nium of the corpus callosum, the total and right cerebral re-
gions and the right caudate.
Correspondence to: Dr. L.G. Almeida Montes, Departamento de Investigación del Centro Estatal de Salud Mental, Servicios de Salud del
Estado de Querétaro & Unidad de Investigación en Neurodesarrollo Dr. Augusto Fernández Guardiola, Instituto de Neurobiología Campus
Juriquilla, Querétaro, Universidad Nacional Autónoma de México; firstname.lastname@example.org
J Psychiatry Neurosci 2010;35(4):238-46.
Submitted Aug. 17, 2009; Revised Dec. 28, 2009, Mar. 13, 2010; Accepted Mar. 15, 2010.
Grey matter in adults with attention deficit hyperactivity disorder
J Psychiatry Neurosci 2010;35(4)
However, another meta-analysis that included 7 VBM
studies showed that the putamen and globus pallidus were
smaller in youth (9.9–15.4 yr) with ADHD.7A more recent
study that involved manual tracing and large-deformation
diffeomorphic metric surface mapping in 47 children with
ADHD and 66 healthy controls found that the putamen, cau-
date and globus pallidus were smaller and abnormally
shaped in children with ADHD.5These contradictory find-
ings stress the need for further research.
The abnormalities in the volume of the caudate nucleus
and other basal ganglia8make sense because these regions
have a role in diverse cognitive functions (e.g., language,9
learning and memory,10,11attention12and control of behav-
ioural responses13,14 ). The results of diverse studies of the
anatomic features of the caudate in ADHD patients have
been contradictory. Some studies have reported that the right
caudate nucleus is smaller in children with ADHD,4,15–17
whereas others have found that only the left caudate is
smaller in ADHD individuals5or that there is no difference.18
Another study found that the total volume of the caudate
was smaller in individuals with ADHD but that this differ-
ence disappeared during adolescence.19
Structural studies involving adults with ADHD are lim-
ited, despite the fact that the prevalence of adult ADHD in
the general population is 4.4%20and only about 10% of pa-
tients with childhood ADHD achieve functional remission at
18–20 years of age.21These findings clearly support the pres-
ence of ADHD in adults.20,22,23There have been 4 structural
MRI reports regarding morphologic abnormalities in adults
with ADHD.24–27Two studies did not report an analysis of the
subcortical structures,24,25and the other 2 studies26,27reported
that there was no difference in the volume of the caudate nu-
cleus between adults with ADHD and healthy individuals.
It is important to mention that the latter 2 studies26,27used
nearly identical sample populations, which suggests that too
few adults with ADHD have been studied to yield definite
conclusions about the structural features of this disease in
adults. Additionally, to the best of our knowledge, there are
no published studies investigating a correlation between the
severity of ADHD and structural measures of the caudate,
and there have been no straightforward comparisons be-
tween adults with ADHD and controls by sex performed in
an independent fashion. Therefore, we attempted to study
the structural features of adults with ADHD because, al-
though ADHD is considered a primarily childhood disorder,
it is important to acknowledge the low rate of functional re-
mission and the few available data about the structural fea-
tures of ADHD in adulthood.
Our aims were to compare the concentration of grey mat-
ter and the volume of the caudate nucleus in adults with
ADHD and to compare these characteristics by sex.
We included 20 unmedicated adults with ADHD, combined
type, diagnosed according to the Diagnostic and Statistical Man-
ual of Mental Disorders, 4th Edition, Text Revised (DSM-IV-TR)
criteria and the Mini International Neuropsychiatric Interview
plus version 5.0 (MINI).28We included patients aged 25–35
years, and 50% were women. We included 20 healthy individ-
uals as controls, who were matched to the ADHD patients by
age, sex, body mass index (BMI) and intelligence quotient (IQ).
We excluded individuals with a current or previous neuro-
logic or psychiatric disease other than ADHD, general medical
illness, an IQ less than 85 points, a history of substance abuse
or dependence or stimulant treatment, or any abnormality on
the MRI scan. We also excluded patients who met the DSM-
IV-TR criteria for ADHD, predominantly inattentive type, and
ADHD, predominantly hyperactive/impulsive type.
A certified neuroradiologist (A.F.-B.), who was unaware of
the individual’s identity, evaluated all MRI scans. The control
and ADHD individuals were recruited from the general com-
munity of the urban areas of Querétaro City and México City
by means of an open invitation poster. The study took place
from March 2006 to February 2008.
After having fully explained the study to all participants,
written informed consent was obtained. Certified physicians
obtained a full medical history and performed a physical ex-
amination of each participant. The Institutional Review Board
of the General Hospital of Querétaro, México, approved the
study protocol and the informed consent document.
The diagnosis of ADHD was made using the MINI-plus
(Spanish version) for all participants by 2 experienced, certi-
fied psychiatrists. The kappa agreement index for the diagno-
sis of adult ADHD between the 2 psychiatrists was 0.85 (p <
0.001). To quantify the severity of ADHD and to correlate
severity with the volumes of the brain structures, we used
both versions of the Friederichsen, Almeida, Serrano, Cortes
Test (FASCT):22the self-reported (FASCT-SR) and the ob-
server (FASCT-O) scales. The FASCT scale was specifically
developed to assess ADHD in adults.
The mother of each patient completed the FASCT-O. Al-
though the FASCT was designed to screen and measure the
severity of ADHD in adults, the agreement kappa indices for
the diagnosis of ADHD between the semistructured inter-
view (MINI-plus) and a FASCT-SR or a FASCT-O score of 23
points or greater were 0.82 and 0.88, respectively. The
FASCT-SR has 3 factors: hyperactivity and deficits in mem-
ory; organization and functional impairment; and low frus-
tration tolerance. The FASCT-O scale has 4 factors: hyperac-
tivity and memory; organization and functional impairment;
low frustration tolerance; and legal problems. More detailed
information about the FASCT scale has been published else-
where.22All participants were tested on the Weschler Adult
Intelligence Scale, 3rd edition (WAIS-III)29by a certified
A 1-T Philips new Intera MRI machine (release 10.3; Philips
Medical Systems) was used for all scans. A fast-field echo T1
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28.Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-Interna-
tional Neuropsychiatric Interview (M.I.N.I.): the development and
validation of a structured diagnostic psychiatric interview for
DSM-IV and ICD-10. J Clin Psychiatry 1998;59 Suppl 20:22-33; quiz
Weschler D. Weschsler adult intelligence scale. 3rd ed. San Antonio
(TX): The Psychological Corporation; 1997.
Ashburner J. A fast diffemorphic image registration algorithm.
31.Klein A, Andersson J, Ardekani B, et al. Evaluation of 14 nonlinear
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Ashburner J, Friston K. Computing average shaped tissue proba-
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Davatzikos C, Genc A, Xu D, et al. Voxel based morphometry us-
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35.Feinstein A. Part II. Comparing two groups of data. In: Principles of
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36.Filipek PA, Kennedy DN, Caviness VS Jr, et al. Magnetic reso-
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Friston K. A short history of SPM. In: Friston K, Ashburner J,
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Segall JM, Turner JA, van Erp TG, et al. Voxel-based morphometric
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J Psychiatry Neurosci 2010;35(4)
Almeida Montes et al.
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