Journal of Child Psychology and Psychiatry 48:12 (2007), pp 1251–1258 doi:10.1111/j.1469-7610.2007.01799.

Structural brain abnormalities in adolescents

with autism spectrum disorder and patients
with attention deficit/hyperactivity disorder
Sarah Brieber,1,3,4 Susanne Neufang,1,3,4 Nicole Bruning,2 Inge Kamp-Becker,6
Helmut Remschmidt,6 Beate Herpertz-Dahlmann,2 Gereon R. Fink,3,4,5 and
Kerstin Konrad1,3,4
1
Child Neuropsychology Section, Department of Child and Adolescent Psychiatry, University Hospital Aachen,
Germany; 2Department of Child and Adolescent Psychiatry, University Hospital Aachen, Germany; 3Institute of
Neuroscience and Biophysics, Department of Medicine, Research Centre Jülich, Germany; 4Brain Imaging Centre
West, Research Centre Jülich, Germany; 5Department of Neurology, University Hospital Köln, Germany; 6Depart-
ment of Child and Adolescent Psychiatry, Philipps University Marburg, Germany

Background: Although autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder
(ADHD) are two distinct neurodevelopmental diseases, they share behavioural, neuropsychological and
neurobiological characteristics. For the identification of endophenotypes across diagnostic categories,
further investigations of phenotypic overlap between ADHD and autism at the behavioural, neurocog-
nitive, and brain levels are needed. Methods: We examined regional grey matter differences and
similarities in children and adolescents with ASD and ADHD in comparison to healthy controls using
structural magnetic resonance imaging (MRI) and voxel-based morphometry. Results: With regard
to clinical criteria, the clinical groups did not differ with respect to ADHD symptoms; however, only
patients with ASD showed deficits in social communication and interaction, according to parental
rating. Structural abnormalities across both clinical groups compared to controls became evident as
grey matter reductions in the left medial temporal lobe and as higher grey matter volumes in the left
inferior parietal cortex. In addition, autism-specific brain abnormalities were found as increased grey
matter volume in the right supramarginal gyrus. Conclusions: While the shared structural deviations
in the medial temporal lobe might be attributed to an unspecific delay in brain development and might
be associated with memory deficits, the structural abnormalities in the inferior parietal lobe may cor-
respond to attentional deficits observed in both ASD and ADHD. By contrast, the autism-specific grey
matter abnormalities near the right temporo-parietal junction may be associated with impaired ‘theory
of mind’ abilities. These findings shed some light on both similarities and differences in the neurocog-
nitive profiles of ADHD and ASD patients. Keywords: ADD/ADHD, autistic disorder, structural MRI,
VBM. Abbreviations: ASD: autism spectrum disorder; ADHD: attention deficit/hyperactivity disorder;
VBM: voxel-based morphometry; MRI: magnetic resonance imaging.

Autism spectrum disorder (ASD) and attention
deficit/hyperactivity disorder (ADHD) are two of the
most frequent neurodevelopmental disorders. While
the main symptoms of ASD are repetitive, stereo-
typed behaviour and impairments in social interac-
tion and communication (American Psychiatric
Association, 1994), ADHD is characterised by a
symptom triad of inattention, hyperactivity and
impulsivity (American Psychiatric Association,
1994). Despite clear clinical boundaries between
both syndromes, inattention and hyperactivity are
also common among children with autism (Sturm,
Fernell, & Gillberg, 2004). Nevertheless, a diagnosis
of ADHD is precluded, under both DSM-IV and ICD-
10 criteria, if symptoms are better accounted for by
autism or pervasive developmental disorder (Amer-
ican Psychiatric Association, 1994; World Health
Organization, 1993). However, there are a number of
behavioural, cognitive, and neurobiological deficits
present in both disorders that suggest at least some
Conflict of interest statement: No conflicts declared.
 2007 The Authors
Journal compilation  2007 Association for Child and Adolescent Mental Health.
Published by Blackwell Publishing, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main Street, Malden, MA 02148, USA
degree of phenotypic overlap between ADHD and
ASD. First, children and adolescents with ASD show
some ADHD typical behaviour, such as attention
deficits, impulsivity or hyperactivity (Goldstein &
Schwebach, 2004; Schatz, Weimer, & Trauner,
2002). Furthermore, in both disorders ADHD
symptomatology responds well to stimulant medi-
cation (Handen, Johnson, & Lubetsky, 2000). Vice
versa, patients with ADHD also show problems in
social interaction and communication, albeit to a
smaller degree than patients with ASD (Clark, Fee-
han, Tinline, & Vostanis, 1999; Geurts et al., 2004a;
Hattori et al., 2006). Secondly, on the neuropsy-
chological level, executive functions, such as flex-
ibility, planning, inhibition, theory of mind (ToM)
abilities and working memory, have been described
to be impaired in both disorders (Buitelaar, van der
Wees, Swaab-Barneveld, & van der Gaag, 1999;
Geurts, Verte, Oosterlaan, Roeyers, & Sergeant,
2004b; Happé, Booth, Charlton, & Hughes, 2006;
Sergeant, Geurts, & Oosterlaan, 2002). Thirdly, both
disorders manifest in early childhood and affect
1252 Sarah Brieber et al.
males more often than females (Fombonne, 2003).
Finally, a strong genetic component is assumed for
both disorders and a recent linkage study indicates
an overlap of the underlying susceptibility genes
(Smalley et al., 2002) located on chromosome 16p13.
The reported genetic, neuropsychological and
behavioural overlap between ASD and ADHD leads
to the assumption of similarities across the two
different disorders with regard to brain structure
and function. Interestingly, there is only one recent
explorative MR spectroscopy study which has
directly compared cerebral white matter metabolite
concentration in both groups, suggesting no common
metabolite deficit present in ASD and ADHD (Fayed
& Modrego, 2005).
In ADHD, many studies have confirmed brain
abnormalities within the fronto-striatal circuitries
(Seidman, Valera, & Makris, 2005). In ASD, studies
have revealed various brain abnormalities, but the
results are still controversial. Neuroimaging studies
demonstrated regional volume differences in several
regions, e.g., the cerebellum, limbic system, as well
as frontal and temporal areas (Brambilla et al.,
2003). The previous anatomical and functional
studies that examined the two patient groups sep-
arately suggest some shared structural abnormali-
ties in the frontal cortex. Nevertheless, the
inconsistency of the results reported precludes any
conclusions and therefore a direct comparison of
both clinical groups within a standardised study
protocol seems to be mandatory. The identification of
overlapping and disease-specific brain abnormalities
might help to explain similarities and differences in
the neurocognitive profiles of ADHD and ASD
patients and thereby point to interesting neurobio-
logical endophenotypes across different diagnostic
categories.
Thus, the present study was designed to compare
regional grey matter volumes between patients with
ADHD and patients with ASD, using voxel-based
morphometry (VBM), compared to healthy controls. In
line with previous neuroimaging studies we expected
to find primarily fronto-striatal abnormalities in
ADHD and primarily fronto-temporal abnormalities
in ASD, among other and more widespread structural
deficits. Based on neuropsychological findings
pointing to executive dysfunction and ToM deficits
present in both disorders, we additionally assumed
that we would find shared grey matter abnormalities,
particularly within the prefrontal cortex.
Methods
Subjects
Fifteen children and adolescents fulfilling the dia-
gnostic criteria for ASD (13 Asperger syndrome, 2 high-
functioning autism), 15 patients with a diagnosis of
ADHD and 15 healthy controls (Con) were recruited for
the study. Experienced clinicians reviewed the clinical
Journal compilation  2007 Association for Child and Adolescent Mental Health.
diagnosis according to the standard criteria of ICD-10
(World Health Organization, 1993) and DSM-IV (Amer-
ican Psychiatric Association, 1994) and all subjects
underwent an extensive psychiatric and neurological
examination. Their psychiatric classification was then
determined on the basis of a semi-structured diagnostic
interview (K-SADS-PL; Kaufmann et al., 1997; German
translation: Delmo, Weiffenbach, Gabriel, Stadler, &
Poustka, 2001). In the autistic group, the expression of
the autistic symptoms was further assessed by the
German version of the Autism Diagnostic Observation
Scale (ADOS-G; Lord et al., 2000) and a semi-struc-
tured autism-specific parent interview (ADI-R; LeCou-
teur et al., 1989) both conducted by trained examiners
(N.B.; I.K.-B.). Diagnoses of Asperger syndrome and
high-functioning autism were differentiated by
the presence or absence of a significant delay in the
acquisition of spoken language (Howlin, 2003). The
anatomical scans were collected from patients and
controls included in ongoing functional imaging studies
(Konrad, Neufang, Hanisch, Fink, & Herpertz-Dahl-
mann, 2006; Manjaly et al., 2007; Hübner et al., in
preparation) in our department. Data were selected on
the basis of quality of the structural MRI scans, age, IQ,
handedness and exclusion criteria for comorbid condi-
tions. All subjects were male, right-handed, had an
intelligence quotient (IQ) above 80 and were between 10
and 16 years old. Additional exclusion criteria were any
potentially confounding psychiatric diagnoses such as
psychosis, mania, major depression, conduct disorder
or substance abuse. The subjects with ASD did not fulfil
the diagnostic criteria for ADHD and, vice versa, ADHD
subjects did not fulfil criteria of any pervasive develop-
mental disorder (PDD). Two ASD subjects were taking
atypical neuroleptic medication (risperidone) and 10
subjects with ADHD were currently on psychostimu-
lants (methylphenidate). The stimulant medications
were discontinued three days before the scanning
procedure. Handedness was controlled using the
Edinburgh Handedness Inventory and IQ was meas-
ured with the Culture Fair Intelligence Test 20 (Weiß,
1998). The three groups were comparable with regard to
age, IQ and handedness. The study was approved by
the Medical Ethics Committee of the University Hospital
of Aachen, and all children and their parents or care-
givers gave their written consent after having been in-
formed about the details and the purpose of this study.
(For further information about the sample characteris-
tics, see Table 1 in the supplemental appendix.).
All parents of the autistic group and 10 parents of the
ADHD group completed the German version of the
Autism Screening Questionnaire (ASQ; Boelte, Crece-
lius, & Poustka, 2000). Additionally, 11 parents of the
ADHD group and 10 parents of the autism group com-
pleted a German Parental Report on ADHD symptoms
according to DSM-IV and ICD-10 (FBB-HKS; Döpfner &
Lehmkuhl, 1998), which consists of the two subscales
inattention and hyperactivity/impulsivity.
Volumetric analyses
MRI brain scans were obtained with a Siemens
1.5 Tesla scanner. We obtained high-resolution,
T1-weighted structural brain images using a standard
MP-RAGE (magnetisation-prepared, rapid acquisition
 2007 The Authors

gradient echo) sequence with the following parameters:
TR ¼2200 ms, TE ¼ 3.93 ms, flip angle a ¼ 15 ;
FOV ¼256 mm; matrix ¼ 180 · 256 mm2; 160 slices,
slice thickness 1 mm, inter-slice gap ¼ .5 mm.
Optimised protocol for the VBM procedure was
applied to our data (Ashburner & Friston, 2000; Good et
al., 2001) using SPM2 (Statistical Parametric Mapping
software, SPM; Wellcome Department of Imaging Neu-
roscience, London, UK) based on Matlab 6.5 (The
Mathworks Inc., Natick, MA, USA). In a first step we
created customised templates from all 45 anatomical
images, including a T1- and grey matter (GM)- template.
Further, the optimised VBM procedure involved the
processing steps segmentation, normalisation, modu-
lation and smoothing with a 12 mm FWHM (full-width
half-maximum) Gaussian kernel.
Age, IQ, ASQ scores, FBB-HKS sub- and total scores,
global GM, white matter (WM) and cerebral spinal fluid
(CSF) volumes were compared using analysis of vari-
ance (ANOVA) and post-hoc comparisons. In addition,
correlation analyses were calculated between all these
measures and Bonferroni corrections for inflated Type I
error were applied in order to control for the number of
analyses conducted.
Since previous structural imaging studies on ADHD
and ASD reported heterogeneous findings and rather
widespread brain abnormalities present in both clinical
groups we decided against a ‘region of interest’-based
analysis of MRI data.
The regional-specific differences in GM volumes
between the clinical groups and the controls were as-
sessed using analysis of covariance (ANCOVA; ASDvs-
Con; ADHDvsCon), with total brain volume as a
covariate of no interest. In order to search for correla-
tions between structural abnormalities in GM and
clinical symptoms (ASQ, FBB-HKS inattention, FBB-
HKS hyperactivity/impulsivity scores), we used simple
regression analyses. Finally, we used a conjunction
analysis (based on an ANCOVA including all groups), as
introduced by Nichols, Brett, Andersson, Wager, and
Poline (2005), to find brain areas that were reduced or
increased in both disorders compared to the healthy
controls (ASDvsCon\ADHDvsCon) or that were spe-
cifically abnormal in one clinical group (ASDvsCon\AS-
DvsADHD; ADHDvsCon\ADHDvsASD). For all analyses,
we used height threshold at p < .001 uncorrected for
multiple comparison with an extent threshold of 10
voxels.
Results
ADHD and ASD subjects did not differ with respect
to the parental rating of ADHD behaviour (FBB-
HKS). Note that on a symptom level, 5 children with
ASD scored above the 90th percentile according to
the FBB-HKS and showed more than 6 symptoms on
either the hyperactive/ impulsive symptom list or the
inattention symptom list. Both clinical groups,
however, differed with respect to the behavioural
ratings of autistic symptoms (ASQ; see Table 2 in the
supplemental appendix).
No significant correlation coefficients were found
between the total volumes of GM, WM or CSF and the
 2007 The Authors
Journal compilation  2007 Association for Child and Adolescent Mental Health.
Structural brain abnormalities in ASD and ADHD 1253
IQ, age or symptom severity scores derived from the
parental questionnaires. In addition, no significant
group differences emerged with regard to total
volume of GM, WM or CSF (GM: F ¼ 2.083, df ¼ 44,
p ¼ .137; WM: F ¼ 1.315, df ¼ 44, p ¼ .279; CSF:
F ¼ 2.53, df ¼ 44, p ¼ .253).
Group-specific and shared abnormalities in grey
matter density
Subjects with ASD showed significantly reduced GM
volumes compared to healthy controls in bilateral
inferior temporal gyrus and hippocampus-amygdala
complex, left middle occipital gyrus and left premotor
gyrus. In addition, an increase in the right supra-
marginal gyrus and in the left postcentral gyrus was
found (Table 3 in the supplemental appendix).
In comparison to the healthy controls, subjects
with ADHD showed a decrease of GM volumes in the
bilateral caudate nucleus, bilateral hippocampus,
right middle frontal gyrus, left insula, left superior
temporal gyrus and left middle occipital gyrus. GM
increases were found in the bilateral superior pari-
etal and postcentral gyrus and the left middle cin-
gulate, precuneus and inferior parietal gyrus
(Table 3, supplemental appendix).
The conjunction analysis revealed that the volume
of the left hippocampus-amygdala complex was
reduced and the left inferior parietal gyrus/postcen-
tral gyrus was increased in both clinical groups com-
pared to healthy controls. In addition, the ASD group
showed increased volume in the right supramarginal
gyrus compared to both ADHD patients and the con-
trols (Figure 1 and Table 1), while no ADHD-specific
GM abnormalities were found when compared to ASD
patients and controls simultaneously.
Effects of ADHD and ASD symptom severity
A negative correlation between regional GM volume
and inattentive symptoms, i.e., high scores on the
FBB attention subscale, for both clinical groups was
seen in the left middle frontal gyrus (x,y,z:
)29,13,64; k ¼ 226 voxel; z ¼ 3.87). No other sig-
nificant correlations between FBB-HKS scores and
GM volumes were found (see Figure 2).
The simple regression analysis of GM volume and
behavioural ratings of autistic behaviour across both
clinical groups also revealed no significant correla-
tion. (For further information see Tables 2 and 3 in
the supplemental appendix).
Discussion
In the present study, we compared GM volumes in
patients with ASD and ADHD to identify shared and
disease-specific brain abnormalities. In line with
recent studies (e.g., Schatz et al., 2002), both groups
showed comparable symptoms of inattention and
1254 Sarah Brieber et al.

(a) (b) (c)

Figure 1 GM abnormalities in patients with ASD and ADHD as revealed by conjunction analysis. Brain areas with
significant GM differences (a) specific increases in ASD compared to controls and compared to ADHD patients (b)
shared increases in patients with ASD and ADHD compared to controls (c) shared decreases in patients with ASD and
ADHD compared to controls, superimposed on the coronal view of the group mean image. A statistical threshold of
p < .005 was used for display purposes; peaks reaching statistical significance are listed in Table 1

Table 1 Regions of significant grey matter differences (p < .001 icantly smaller extent than in PDD and although they
uncorrected for multiple comparisons; extent threshold: 10 differed from the healthy group, the PDD-related
voxel) of the conjunction analysis
symptoms did not reach the threshold of DSM-IV
MNI criteria.
coordinates With regard to structural brain abnormalities, we
Voxel found, as expected, fronto-striatal abnormalities in
Anatomical region numbers Z-score x y Z
the ADHD group and fronto-temporo-limbic abnor-
ASD>Con\ASD>ADHD malities in the ASD group in comparison to a healthy
Right supramarginal gyrus 50 3.71 47 )39 29 control group. In contrast to our hypothesis, we did
ADHD>Con\ASD>Con not find a shared deficit in the prefrontal cortex.
Left inferior parietal/ 65 3.37 )31 )38 51
postcentral gyrus
However, shared brain abnormalities were present in
Con>ADH\Con>ASD the medial temporal lobe and the inferior parietal
Left hippocampus-amygdala 18 3.16 )31 )7 )17 gyrus. In addition, we found an autism-specific
increase of grey matter in the supramarginal gyrus
and a relationship between the GM reduction of the
left middle frontal/premotor gyrus and severity of
attentional deficits.
The reported fronto-striatal abnormalities in the
ADHD group are consistent with several imaging
studies and are likely to underlie the impaired
attentional inhibitory control mechanisms associ-
ated with the disorder (Durston, 2003; Konrad et al.,
2006). The finding of additional structural abnor-
malities of parietal cortex are also in accordance with
recent studies (Sowell et al., 2003) that indicate
abnormalities in cortical regions associated with
attentional functions. By contrast, the GM reduction
in the left occipital lobe and the left hippocampus in
Figure 2 Significant correlations between a decrease in the ADHD group have not been reported previously
GM and the severity of inattentive symptoms in the and merit further investigation. But in line with this
ADHD and the ASD group rendered on a MNI standard finding it is important to note that Castellanos et al.
brain. A statistical threshold of p < .005 was used for (2002) showed volume reductions in all four lobes in
display purposes
ADHD, rather than a limited volume reduction only in
the fronto-striatal networks. Moreover, recent func-
hyperactivity/impulsivity according to parental tional imaging studies suggest activation of more
ratings. However, in contrast to previous studies diffuse and widespread brain areas in ADHD than in
(Clark et al., 1999), no deficits in social commu- controls (Durston, 2003; Konrad et al., 2006).
nication and interaction were found in the ADHD Also consistent with our hypotheses, the main
group when compared to cut-off scores of the ASQ. findings of GM reductions in ASD compared
This might be explained by the fact that social inter- to healthy controls indicate brain abnormalities in
action abilities are only mildly reduced in ADHD and the temporal and the frontal lobes. In addition, we
we did not directly compare the ASQ scores of the reported abnormalities in the hippocampus-amyg-
clinical groups to the normal control group. For dala complex and the occipital cortex. Several
example, Hattori et al. (2006) reported that social imaging studies postulate an involvement of these
impairment problems in ADHD occurred to a signif- structures in the pathophysiology of autism and
 2007 The Authors
Journal compilation  2007 Association for Child and Adolescent Mental Health.

social cognition (Abell et al., 1999; Waiter et al.,
2004). Furthermore, the conjunction analysis re-
vealed an autism-specific increase of GM in the right
supramarginal gyrus near the temporo-parietal
junction. Functional imaging studies suggest that
this structure might be relevant for impaired cog-
nitive functions, such as mentalising, imitation and
ToM abilities (Castelli, Frith, Happé, & Frith, 2002;
Saxe & Kanwisher, 2003; Vogeley et al., 2001).
In addition, the conjunction analyses revealed a
shared reduction in the left hippocampus-amygdala
complex in ASD and ADHD. Such structural brain
abnormalities have also been described in other
psychiatric disorders, such as schizophrenia (Sim et
al., 2006) and bipolar disorders (Frazier et al., 2005).
Therefore, the observed reduction might reflect
either an unspecific psychiatric effect or a general
delay in brain development. In accordance with this
assumption, data from recent cross-sectional and
longitudinal studies on normal brain development in
children and adolescents suggest that older male
adolescents have a significantly greater left hippo-
campus than younger ones (Suzuki et al., 2005),
which might also point to the typical male predom-
inance of these neuropsychiatric diseases associated
with hippocampal abnormalities. Recently, it has
been also suggested that the presence of the met-
allele of the brain-derived neurotrophic factor
(BDNF) gene is associated with an 11% reduction
of the hippocampal formation volume in healthy
volunteers and may thus represent a vulnerability
factor for the development of dysfunction of this
brain region (Bueller et al., 2006). In ADHD, con-
flicting data exist as to whether ADHD is associated
with BDNF polymorphisms (Friedel et al., 2005). By
contrast, in ASD recent findings suggest that the
BDNF and autoantibodies to neural antigens are
elevated in sera of children with autistic spectrum
disorders, Landau–Kleffner syndrome, and epilepsy
(Connolly et al., 2006). Thus, one may speculate that
genetic variations in the BDNF gene present in both
clinical disorders might contribute to structural
brain abnormalities in the hippocampal formation.
In line with this assumption, it has been demon-
strated that BDNF genotypes are associated with
medial-temporal-cortex mediated declarative mem-
ory processes (Egan et al., 2003), which have been
shown to be impaired in both ADHD (Westerberg,
Hirvikoski, Forssberg, & Klingberg, 2004) and ASD
patients (Salmond et al., 2005).
Furthermore, we found shared brain abnormal-
ities across both diagnostic groups with an increase
of GM in left inferior parietal/postcentral gyrus. The
parietal cortex plays an important role in circuits
that are activated by tasks that acquire attention. In
addition, several functional imaging studies showed
typical fronto-striatal underactivation in ADHD
accompanied by an increased activation in parietal
regions (Konrad et al., 2006; Rubia et al., 1999) and
it is speculated whether this is a ‘beneficial’
 2007 The Authors
Journal compilation  2007 Association for Child and Adolescent Mental Health.
Structural brain abnormalities in ASD and ADHD 1255
compensatory activation of the attention-switching
network in executive attention tasks. Booth et al.
(2004) showed that lower accuracy in a visual search
task was associated with greater activation in bilat-
eral superior parietal lobule and right lateral pre-
motor cortex in ADHD. Also in autism, a recent study
by Belmonte and Yurgelun-Todd (2003) indicated a
heightened and abnormally variable activity in the
parietal cortex in a spatial attention task. Moreover,
Schmitz et al. (2006) reported an increased brain
activation in the parietal lobe of autistic patients in a
Set Shifting task and suggest that this is possibly
related to structural and metabolic abnormalities in
this brain area. Thus, shared structural brain
abnormalities in the parietal cortex seemed to co-
incide with increased brain activation patterns
present in both ADHD and autism. Unfortunately,
our data do not suggest a causative direction of this
association; thus, increased GM volumes may result
from increased brain activity or vice versa functional
brain abnormalities might be caused by structural
deficits.
A significant correlation of inattentive symptoms
with a GM reduction was also observed in the left
middle frontal gyrus near the premotor cortex across
both disorders. Reductions in premotor areas have
already been reported by Mostofsky, Cooper, Kates,
Denckla, and Kaufmann (2002) in patients
with ADHD. It has been suggested that deficits in
response inhibition in ADHD can be attributed to the
premotor area, beside others, mediated by overflow
movements and deficits in motor response inhibi-
tion. These shared abnormalities in parietal
and frontal cortex might thus reflect deficits in an
attentional network in ASD and ADHD that is
involved in top-down selection of stimuli and
responses (Corbetta & Shulman, 2002).
Although frontal cortex abnormalities were found
in both patient groups when compared to normal
controls, we could not find a direct overlap of pre-
frontal brain regions in the conjunction analysis.
This is in line with the neuropsychological finding
that executive function deficits, although present in
both groups, might differ between both diagnostic
categories: while in ASD in particular deficits
in flexibility and planning were observed, ADHD
patients in particular showed impaired inhibition
processes underlying their executive function defi-
cits (Ozonoff & Jensen, 1999). Note, however, that
more recent studies suggested that inhibition defi-
cits might be impaired in both disorders and are not
specific for ADHD (Geurts et al., 2004; Goldberg
et al., 2005). Thus future studies that focus on
neural correlates of inhibitory control in both ADHD
and ASD patient groups as well as the structure–
function relationship in prefrontal cortex are needed.
While the present study is the first to directly
compare GM volumes of ASD, ADHD and controls by
using optimised voxel-based morphometry, a num-
ber of limitations should be considered. As we
1256 Sarah Brieber et al.
investigated a relatively small cohort, studies with
larger samples are needed to replicate our results.
Also, there were some missing data with regard to
the parental questionnaires, which reduced the
number of subjects that were included in the simple
regression analysis. Statistical inferences were
based on a threshold uncorrected for multiple com-
parisons, which could have increased the number of
the false positive findings.
Conclusion
In the present study we found no specific marker in
grey matter for the ADHD group. Inattention and
hyperactivity/impulsivity are the main symptoms of
ADHD and are postulated to be modulated by
abnormal fronto-striatal circuits. Our study con-
firms these findings in patients with ADHD in com-
parison to controls, but in contrast to patients with
autism spectrum disorder the deficits were not able
to distinguish between the two disorders. On the
other hand, deficits in social communication and
interaction, repetitive, stereotype behaviour and a
grey matter volume increase in the right supramar-
ginal gyrus were found to be specific for children
with autism spectrum disorders.
Furthermore, our present results point to shared
brain abnormalities within the medial temporal and
inferior parietal lobe in autism and ADHD and are in
line with a number of studies which have focused
on one clinical group only. Future research should
focus on the investigation of the relationship of their
neuropsychological profiles and neurobiological
endophenotypes. Thus, our findings may not only
help to further elucidate the neural basis of autistic
and ADHD symptoms but may also have clinical
implications with regard to the diagnosis and treat-
ment of patients with neurodevelopmental disorders.
For example, our findings of shared brain abnor-
malities in the medial temporal lobe and the inferior
parietal cortex suggest that attention and memory
processes in childhood psychiatric disorders across
diagnostic categories should be diagnosed more
carefully. Such an approach could also result in the
development of more specific intervention proced-
ures (including cognitive training, neurofeedback
procedures and pharmacological interventions)
within an individualised, optimised treatment pro-
tocol based on neuroscientific findings.
Supplementary material
The following supplementary material is available for
this article:
Table 1 Sample characteristics of all three groups.
Table 2 Median of the parental rating scales for the
ADHD and the ASD group.
Table 3 Regions of significant grey matter differ-
ences (p < .001 uncorrected for multiple compar-
Journal compilation  2007 Association for Child and Adolescent Mental Health.
isons; extent threshold: 10 voxel) between the three
groups.
This material is available as part of the online
article from: http://www.blackwell-synergy.com/
doi/abs/10.1111/j.1742–4658.2006.01799.x (This
link will take you to the article abstract).
Please note: Blackwell Publishing are not respon-
sible for the content or functionality of any supple-
mentary materials supplied by the authors. Any
queries (other than missing material) should be
directed to the corresponding author for the article.
Acknowledgements
This study was funded by a grant to K.K. and G.R.F.
of the Interdisciplinary Center of Clinical Research
Aachen (IZKF N60 and N65) in Germany. K.K.,
B.H.-D. and G.R.F. gratefully acknowledge further
support by the Deutsche Forschungsgemeinschaft
(DFG-KFO112). We are grateful to our colleagues
from the MR group and the Cognitive Neurology
group, particularly Peter Weiss-Blankenhorn, for
their support.
Correspondence to
Sarah Brieber, Institute of Neuroscience and Bio-
physics, Department of Medicine, Research Centre
Jülich, 52425 Jülich, Germany; Tel: +49 2461 61
2084; Fax: +49 2461 61 2820; Email: s.brieber@
fz-juelich.de
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