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http://jcn.sagepub.com/Journal of Child Neurology
http://jcn.sagepub.com/content/21/8/701The online version of this article can be found at:
DOI: 10.1177/08830738060210080701
2006 21: 701J Child NeurolMartha Bridge Denckla
Attention-Deficit Hyperactivity Disorder (ADHD) Comorbidity: A Case for ``Pure'' Tourette Syndrome?
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- Aug 1, 2006Version of Record >>
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Special Article
Attention-Deficit Hyperactivity Disorder (ADHD)
Comorbidity: A Case for ‘‘Pure’’ Tourette
Syndrome?
Martha Bridge Denckla, MD
ABSTRACT
More than a decade of research regarding the motoric characteristics of the attention-deficit hyperactivity disorder
(ADHD) that accompanies Tourette syndrome has revealed unique anatomic and neurobehavioral differences and
highlighted the importance of distinguishing children with this form from the 40% of children with Tourette syndrome
who do not have ADHD. This distinction is important in providing guidance to parents and to patients and in formulating
expectations for short- and long-term prognoses. In addition, study methodologies that fail to categorize patients in this
way and instead involve covarying for dimensional symptoms of ADHD obscure biologically distinctive circuits and
clinically meaningful patient characteristics. (J Child Neurol 2006;21:701–703; DOI 10.2310/7010.2006.00164).
Tourette syndrome without comorbid attention-deficit hyperac-
tivity disorder (ADHD) is anatomically distinctive from and
neurobehaviorally less impairing than Tourette syndrome with
co-occurring ADHD. Volumetric magnetic resonance imaging
(MRI), for example, reveals smaller basal ganglia structures in
patients with Tourette syndrome plus ADHD. In contrast, those
with pure Tourette syndrome show an enlarged rostral corpus
callosum and excessive right frontal white matter. Tourette
syndrome plus ADHD makes the rostral corpus callosum appear
to be normal in size. Patients with pure Tourette syndrome show
enhanced motor speed; with comorbid ADHD, as with ADHD
alone, they are slow on timed motor tasks. Although even pure
Tourette syndrome is associated with longer prosaccade
latencies, impaired antisaccade accuracy characterizes anyone
with ADHD. Children with pure Tourette syndrome also seem to
be spared learning disabilities, found in 23% of the entire
Tourette syndrome group (comorbid ADHD included), in written
language expression only. Children with pure Tourette syndrome
show unexpectedly high IQ scores. Interestingly, the data that
have been acquired through the research summarized below
reveal that the characteristics of children with Tourette
syndrome plus ADHD are indistinguishable from those of the
large group of children with ADHD who do not have Tourette
syndrome.1–12 The neuroscientific principle of multiple parallel
circuits—particularly frontostriatal circuits that involve motor
control, cognitive control, and emotional control—helps differ-
entiate children with pure Tourette syndrome from those with
Tourette syndrome plus ADHD.13
VOLUMETRIC MRI
Imaging supports the case for categorizing children with
Tourette syndrome plus ADHD separately from those with either
ADHD or Tourette syndrome alone. Whereas a lack of
asymmetry was the only Tourette syndrome–associated finding,
smaller basal ganglia structures are associated with comorbid
ADHD.1 In a small study of boys matched to our Tourette
syndrome sample during the first 5 years of our research project,
the researchers found that the boys with ADHD had exactly the
same imaging findings as the boys with Tourette syndrome plus
ADHD.2 In a more recent study, the methodology for image
acquisition and measurement differed somewhat, especially
because an updated version of Brain Image software was used.3
In this study, the right caudate volume was smaller in the ADHD
group in children ages 8 to 9.9 years. In contrast, those children
10 years and older within the ADHD group did not have
significantly reduced right caudate volume.
Received March 29, 2006. Accepted for publication April 10, 2006.
From the Kennedy Krieger Institute, Baltimore, MD.
This work was supported by research grants HD 25806 from the NationalInstitute of Child Health and Human Development and NS 35359 and NS043480 from the National Institute of Neurological Disorders and Stroke.
Presented at the Neurobiology of Disease in Children: Symposium onTourette Syndrome, in conjunction with the 34th annual meeting of theChild Neurology Society, Los Angeles, CA, September 28 to October 1,2005. Supported by grants from the National Institutes of Health (grant 1R13 NS40925-01), the Tourette Syndrome Association, and the ChildNeurology Society.
Address correspondence to Dr Martha Bridge Denckla, Kennedy KriegerInstitute, 707 North Broadway, Suite 232, Baltimore, MD 21205. Tel: 443-923-9250; fax: 443-923-9255; e-mail: [email protected].
701
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Another study revealed that the rostral corpus callosum is
enlarged in patients with ‘‘pure’’ Tourette syndrome but not in
patients with Tourette syndrome plus ADHD (in which the
rostral corpus callosum is on the small side and sometimes to a
significant degree, depending on the control group). Para-
doxically, the combined group of Tourette syndrome plus
ADHD shows a ‘‘normal’’ corpus callosum.5 Right frontal white-
matter excess also has been found in the pure Tourette
syndrome group and might account for enlargement of the
rostral corpus callosum.6 The ADHD factor, whether alone or in
combination with Tourette syndrome, seems to be associated
with structural diminution in size.5,6 The pseudonormal corpus
callosum and, indeed, the frontal white matter that results from
the comorbid condition indicate that different pathologic
processes might underlie Tourette syndrome and ADHD and
that when both are present, opposing effects ‘‘cancel out.’’
MOTOR AND OCULOMOTOR FINDINGS IN TOURETTE
SYNDROME
Unexpectedly, the results from the standardized and semiquan-
tified Physical and Neurological Examination for Subtle Signs—
which, in its timed task subdivisions, generates normally
distributed data that yield means and standard deviations—
show that patients with pure Tourette syndrome perform timed
tasks on the faster side of normal, whereas both those with
comorbid ADHD and those with ADHD alone are slower than
normal.7 With respect to oculomotor data, variability in
prosaccade latency and the antisaccade error rate are greater
in the comorbid group, similar to what is independently found in
groups with pure ADHD.8 The only finding within this category
that seems peculiar to pure Tourette syndrome and to Tourette
syndrome plus ADHD (which thus appears to ‘‘adhere’’ to the
diagnosis of Tourette syndrome) is prolongation of latency of
prosaccades.8
COGNITIVE AND ACADEMIC FINDINGS
Compared with their families, that is, unaffected siblings and
parents, children with pure Tourette syndrome have higher IQs
than expected.9 In other words, their IQ scores do not regress to
the mean of their parents’ IQ scores in the way that the scores of
their siblings and most other populations have done. With
respect to learning disabilities, 23% of the Tourette syndrome
group has some kind of learning disability, regardless of ADHD
comorbidity; however, none of the children with pure Tourette
syndrome sampled in our research have been found to have any
learning disabilities.9 The learning disabilities detected in the
Tourette syndrome plus ADHD group are predominantly in the
domain of written language expression, with mathematics and
reading spared.
EXECUTIVE FUNCTION FINDINGS
In our group’s first sample, evaluated from 1990 to 1995, there
was certainly more executive dysfunction found with comorbid
ADHD than there was with pure Tourette syndrome.9,10 The
executive dysfunction found in the Tourette syndrome plus
ADHD group was virtually identical to that found with the ADHD
group.9,10 All groups with Tourette syndrome did, however, show
slow reaction time on the Test of Variables of Attention. Even
those with pure Tourette syndrome showed somewhat more
variable reaction time, although this was not statistically
significant.10 In this first sample, children scored poorly on
letter word fluency; those with pure Tourette syndrome showed
distinctively low output per minute, implying ‘‘bradyphrenia,’’
slow mental fluency or output.9
In our second sample, evaluated from 1995 to 2000, greater
care was taken to screen for and set aside or covary obsessive-
compulsive symptoms, not just obsessive-compulsive disorder.
We found that no member of the group was impaired on the
letter word fluency finding.11 In fact, it was more difficult to find
significant executive dysfunction in this particular sample,
despite having used tests with broader norms. This sample was
characterized by somewhat above-average IQ scores even within
the ADHD group. This might have contributed to the nullification
of executive dysfunction findings. In any event, the findings were
certainly much more subtle. Intrusion errors were elevated in the
Tourette syndrome plus ADHD group on the California Verbal
Learning Test2Children’s Version.11 The Behavior Rating
Inventory of Executive Function had been completed by that
time and was put into effect in this cohort protocol. It was found
that this external observer Behavior Rating Inventory was not
correlated with assessment of executive dysfunction measures in
the laboratory. On the Behavior Rating Inventory of Executive
Function, the Tourette syndrome plus ADHD group showed the
same anomalous indices as did ADHD, whereas the pure
Tourette syndrome group showed only one minor subscale
elevation, on the subscale titled ‘‘Working Memory.’’12 Executive
dysfunction of both the behavior regulation and the cognitive
control variety was rated as a problem by the parents and
teachers of both groups, Tourette syndrome plus ADHD and
ADHD. The work of this epoch indicated that the Behavior
Rating Inventory of Executive Function might indeed be more
sensitive to executive dysfunction than the laboratory tests we
used at that time, but it was again demonstrated that there was
much less to be found in the case of the pure Tourette syndrome
group.
Some unresolved issues from this decade of research
remain, namely, whether bradyphrenia is really a function
of obsessive-compulsive symptomatology, sometimes called
obsessive-compulsive behavior, even when nothing rises to the
level of obsessive-compulsive disorder. The other issue was
whether treatment of obsessive-compulsive disorder with
specific serotonin reuptake inhibitors might subtly affect
cognitive speed and, therefore, make it difficult to research this
issue. Still unresolved is the question of whether Tourette
syndrome plus ADHD is a distinct syndrome, although research
to date appears to indicate that it closely resembles ‘‘garden-
variety’’ ADHD.
Since 2000, research has focused mainly on ADHD. As noted
above, imaging has been used with slight methodologic
modifications and has thus far revealed that the right caudate
nucleus is volumetrically reduced in size in boys with ADHD, a
finding mainly accounted for by those in the younger rather than
the older age group.3
In terms of executive function, response inhibition has been
studied extensively in a large number of children (n 5 58) with
702 Journal of Child Neurology / Volume 21, Number 8, August 2006
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ADHD and in controls (n 5 84) using different types of go/no-go
tasks: one with high working memory demand, one with low
working memory demand, and one with rewards and response
costs that were motivation linked. In children with ADHD,
response inhibition was impaired even when the executive
function demands of the task were minimal (ie, very simple and
with low working memory demands).
In addition, an examination of the discriminant value of
executive function tasks measured in children with ADHD has
been carried out using much larger groups than were previously
available to analyze. Measures of response inhibition are
distinctively effective in discriminating children with ADHD
from controls, whereas other more proactive and elaborate
executive function measures seemed less useful (Wodka et al,
submitted for publication, 2006).14 Probably most significant of
all, there has been evidence for unexpected ‘‘difficulties in
learning’’ among children with ADHD without reading disabilities
using the California Verbal Learning Test2Children’s Version,
alluded to above in terms of the intrusion error elevation found
as one of the few dysexecutive features of our second cohort of
children with Tourette syndrome plus ADHD and ADHD.11
Children with ADHD free of reading disabilities and free of any
implication of any verbal learning disability were impaired
virtually across the board on the California Verbal Learning
Test2Children’s Version.12 Children with ADHD not only
displayed impaired learning characteristics and strategies, they
also had impairments in the level of recall and storage of
information, showing the impact of executive function on the
process of memorization.12
CONCLUSION
Because there are so few anatomic (by imaging) or neurobeha-
vioral abnormalities associated with pure Tourette syndrome, it
is important to inform the parents of these children, who
comprise 40% of all children with Tourette syndrome, that their
future is not burdened with the same issues as those of the
remaining 60% of children who have comorbid ADHD with
Tourette syndrome. Furthermore, programs and treatments for
ADHD associated with Tourette syndrome need not differ from
those provided for children with ‘‘garden-variety’’ ADHD alone.
References
1. Singer HS, Reiss Al, Brown JE, et al: Volumetric MRI changes inbasal ganglia of children with Tourette syndrome. Neurology
1993;43:950–956.
2. Aylward EH, Reiss AL, Reader MJ, et al: Basal ganglia volumes inchildren with attention deficit hyperactive disorder. J Child
Neurol 1996;11:112–115.
3. Kates WR, Warsofsky IS, Patwardhan A, et al: AutomatedTalairach atlas-based parcellation and measurement of cerebrallobes in children. Psychiatry Res 1999;91:11–30.
4. Baumgartner TL, Singer HS, Denckla MB, et al: Corpus callosummorphology in children with Tourette syndrome and attentiondeficit hyperactivity disorder. Neurology 1996;47:1–6.
5. Fredericksen KA, Cutting LE, Kates WR, et al: Disproportionateincreases of white matter in right frontal lobe in Tourettesyndrome. Neurology 2002;58:85–89.
6. Schuerholz LJ, Cutting L, Mazzocco MM, et al: Neuromotorfunction in children with Tourette syndrome with and withoutattention deficit hyperactivity disorder. J Child Neurol 1997;12:438–442.
7. Mostofsky SH, Lasker AG, Singer HS, et al: Oculomotorabnormalities in boys with Tourette syndrome with andwithout ADHD. J Am Acad Child Adolesc Psychiatry 2001;40:1464–1472.
8. Schuerholz LJ, Baumgardner TL, Singer HS, et al:Neuropsychological status of children with Tourette syndromewith and without attention deficit hyperactivity disorder.Neurology 1996;46:958–965.
9. Harris EL, Schuerholz LJ, Singer HS, et al: Executive functionin children with Tourette syndrome and/or attention deficithyperactivity disorder. J Int Neuropsychol Soc 1995;1:511–516.
10. Mahone EM, Koth CW, Cutting L, et al: Executive function influency and recall measures among children with Tourettesyndrome or ADHD. J Int Neuropsychol Soc 2001;7:102–111.
11. Mahone EM, Cirino PT, Cutting LE, et al: Validity of the BRIEF inchildren with ADHD and/or Tourette syndrome. Arch Clin
Neuropsychol 2002;17:643–662.
12. Cutting LE, Koth CW, Mahone EM, Denckla MB: Evidence forunexpected ‘‘difficulties in learning’’ in children with attentiondeficit hyperactivity disorder (ADHD) without reading disabilities(RD). J Learn Disabil 2003;36:259–269.
13. Cummings JL: Frontal subcortical circuits and human behavior.Arch Neurol 1993;50:873–880.
14. Wodka EL, Mahone EM, Blankner JG, et al: Evidence thatresponse inhibition is a primary deficit in ADHD. J Clin Exp
Neuropsychol 2006;in press.
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