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http://jcn.sagepub.com/ Journal of Child Neurology http://jcn.sagepub.com/content/21/8/701 The online version of this article can be found at: DOI: 10.1177/08830738060210080701 2006 21: 701 J Child Neurol Martha Bridge Denckla Attention-Deficit Hyperactivity Disorder (ADHD) Comorbidity: A Case for ``Pure'' Tourette Syndrome? Published by: http://www.sagepublications.com can be found at: Journal of Child Neurology Additional services and information for http://jcn.sagepub.com/cgi/alerts Email Alerts: http://jcn.sagepub.com/subscriptions Subscriptions: http://www.sagepub.com/journalsReprints.nav Reprints: http://www.sagepub.com/journalsPermissions.nav Permissions: http://jcn.sagepub.com/content/21/8/701.refs.html Citations: What is This? - Aug 1, 2006 Version of Record >> at TEMPLE UNIV on November 11, 2014 jcn.sagepub.com Downloaded from at TEMPLE UNIV on November 11, 2014 jcn.sagepub.com Downloaded from

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Page 1: Attention-Deficit Hyperactivity Disorder (ADHD) Comorbidity: A Case for ``Pure'' Tourette Syndrome?

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?  

Published by:

http://www.sagepublications.com

can be found at:Journal of Child NeurologyAdditional services and information for    

  http://jcn.sagepub.com/cgi/alertsEmail Alerts:

 

http://jcn.sagepub.com/subscriptionsSubscriptions:  

http://www.sagepub.com/journalsReprints.navReprints:  

http://www.sagepub.com/journalsPermissions.navPermissions:  

http://jcn.sagepub.com/content/21/8/701.refs.htmlCitations:  

What is This? 

- Aug 1, 2006Version of Record >>

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Page 2: Attention-Deficit Hyperactivity Disorder (ADHD) Comorbidity: A Case for ``Pure'' Tourette Syndrome?

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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Page 3: Attention-Deficit Hyperactivity Disorder (ADHD) Comorbidity: A Case for ``Pure'' Tourette Syndrome?

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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Page 4: Attention-Deficit Hyperactivity Disorder (ADHD) Comorbidity: A Case for ``Pure'' Tourette Syndrome?

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

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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.

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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

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