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Keywords:

  • attention deficit–hyperactivity disorder;
  • comorbidity;
  • mental retardation

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Attention deficit–hyperactivity disorder (ADHD) has been noted for its high rate of comorbidity. The present study is the first report in Japan evaluating the proportion of comorbidity in ADHD cases presenting in the clinical setting, aiming at clarifying the picture of ADHD in Japan. The subjects consisted of 68 child and adolescent cases meeting criteria for ADHD (Diagnostic and Statistical Manual of Mental Disorders, 4th edn) under treatment at a child psychiatry clinic (IQ > 50, mental age ≥ 4 years old). Disorders evaluated as comorbid disorders were mood disorders, anxiety disorders, elimination disorders, sleep disorders, tic disorders, oppositional defiant disorder (ODD), conduct disorder (CD), school refusal, and epilepsy. Comorbidity with mood disorders, anxiety disorders, ODD, and CD, were found to be lower than the high rates conventionally reported in North America. The lower age of the present subjects, primarily in infancy and elementary school age with few adolescent cases, and a bias towards milder cases from an outpatient clinic without inpatient facilities are believed to be factors accounting for this disparity. Furthermore, it was a notable fact that mentally delayed cases (IQ: 51–84) amounted to 34% of the cases, indicating the necessity to consider intelligence level when formulating a treatment strategy for ADHD.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Attention deficit–hyperactivity disorder (ADHD) is a syndrome characterized by heterogeneity and involving a high rate of comorbid psychiatric disorders. In their large epidemiological survey, Szatmari et al. found that up to 44% of ADHD children had at least one other psychiatric disorder, 32% had two others, and 11% had at least three other disorders.1 The review by Biederman et al. showed that previous studies had reported 30–50% of ADHD cases to be accompanied by conduct disorders, 15–75% by mood disorders, and 25% by anxiety disorders.2 According to the summary by Barkley 10–40% of ADHD children have anxiety disorders, 9–32% have major depression, 6–20% have bipolar disorder, 54–67% have oppositional defiant disorder (ODD), and 20–56% have conduct disorder (CD).3 Although a high incidence of comorbidity is being reported primarily in North America, ADHD has rapidly become a focus of attention in Japan in the past few years, with concern now extending to the nature of its comorbid disorders.4–6 Study on the comorbidity of ADHD is significant not only for further clarification of ADHD itself but also in terms of treatment methodology.2,7 The present study is the first report in Japan to evaluate the proportion of comorbidity in ADHD cases presenting in the clinical setting, aiming at clarifying the picture of ADHD in Japan.

METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

The subjects consisted of 68 children and adolescents (63 boys, five girls; nine preschool children aged 4–6 years, 50 elementary school children aged 7–12 years, nine adolescents aged 13–19 years; mean age: 9.7 years) satisfying criteria for ADHD according to Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV), under treatment at the Child Psychiatry Clinic of the Toyota-city Child Development Center as of March 2000.

Diagnoses were made following careful interview of the parents, direct observation of the patient's behavior, and interview of the patient by child psychiatrists. Determination of the pervasiveness of the symptoms was made through data on behavior patterns in the group setting collected from kindergarten, day-care, and school staff. All diagnoses had been finalized by the third visit to the clinic.

Patients who had not reached the mental age of 4, and those with IQ under 50 were excluded from the present study, as were those meeting criteria for pervasive developmental disorder.

The cases were then examined in terms of the following: (i) rate of comorbidity; (ii) comparison of comorbidity rate in terms of type of ADHD; (iii) comparison of comorbidity rate between mentally delayed cases and those with normal intelligence; and (iv) other characteristics.

Disorders taken into consideration in the present study were mood disorders (major depressive disorder and bipolar disorder), anxiety disorders, elimination disorders, sleep disorders, tic disorders, ODD, CD, school refusal, and epilepsy. The presence of comorbid disorders was determined through careful collection of data from the parents, patient interview and behavior observation at the time of the survey (March 2000) and from before as judged from medical records, from which the rate of each disorder among all cases was calculated. This value reflects the lifetime prevalence of disorders.

Diagnosis of the comorbid disorders were made according to DSM-IV criteria with the exception of epilepsy and school refusal. School refusal was diagnosed according to Berg's definition as proposed by Elliot.8 School refusal and epilepsy, which are not defined by DSM-IV, were included in the analysis for the following reasons. School refusal is the most widely encountered phenomena in the practice of child and adolescent psychiatry in Japan, long regarded as one of the crucial areas of study, while epilepsy is an integral disorder in terms of children with developmental disorders, often being a target of treatment in the practice of child psychiatry in Japan.

The presence of mental delay was confirmed by standardized intelligence tests (Tanaka-Binet or Wechsler Intelligence Scale for Children–Revised) in 64 of the 68 cases. The four cases in whom parent compliance could not be obtained for testing were judged as being of normal intelligence through ample capacity for conversation in the interview setting, enrolment in regular schools, and absence of notable academic delay.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Rate of comorbidity

Although no comorbidity was recognized in 36 cases, multiple comorbid disorders were noted in several cases (Table 1). The total number of comorbid disorders are shown in Table 2, and the following is a review of the comorbidity by disorder.

Table 1. Presence/absence of comorbidity
No. comorbid disordersNo. cases
036
126
2 4
3 2
Total68
Table 2. Rates of comorbidity
 Comorbidity (n = 68: 63 boys, 5 girls)
n%
  1. DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th edn.

Disorders according to DSM-IV
 Elimination disorders811.8
 Oppositional defiant disorder5 7.4
 Anxiety disorders5 7.4
 Tic disorders4 5.9
 Conduct disorder2 2.9
 Sleep disorders2 2.9
 Bipolar disorder1 1.5
Disorders not included in DSM-IV
 School refusal811.8
 Epilepsy5 7.3
Elimination disorders

Eight cases of elimination disorder were seen (11.8%), including five cases of nocturnal enuresis, two cases of diurnal enuresis, and one case of encopresis.

Oppositional defiant disorder

This was noted in five cases, amounting to 7.4%. The age of onset of all five cases ranged across elementary school age (age 6–10), and the type of ADHD was the combined type. Methylphenidate was effective in all cases. Intelligence was within the normal range in four of the five cases.

Anxiety disorders

Among the five cases of anxiety disorders, no cases of panic disorder, phobia, or obsessive–compulsive disorder were seen. Four cases were found to be of generalized anxiety disorder (all were boys, two were predominantly inattentive-type cases, and two were combined-type cases). The four patients were of a timid nature from infancy, tending to exhibit elevated anxiety in the face of new experiences, exhibiting symptoms such as pollakiuria, school refusal, or clinging to the mother against a background of anxiety.

The other one case was diagnosed as post-traumatic stress disorder (PTSD) arising from the trauma of being bullied in elementary school prior to presentation at Toyota-city Child Development Center.

Tic disorders

There were four cases of tic disorder. Two were cases of Tourette's disorder, and one case each of chronic tic disorder and transient tic disorder. Transient obsessive symptoms were noted in one of the two cases of Tourette's disorder.

Conduct disorder

In the two cases of CD, lying, shoplifting, and nocturnal prowling was noted in one case from the 2nd year in elementary school. Family discord and the father's violent responses to the child were believed to be involved with onset of the disorder.

The other case had frontal lobe epilepsy, exhibiting increase in antisocial behavior such as lying, nocturnal prowling and shoplifting starting in upper elementary school, paralleling the frequent occurrence of seizures. The patient was a sociable child and strong aggression had not been part of his nature. Methylphenidate administration and adjustment in his anticonvulsant medication led to remission of the seizures and improvement of deviant behavior.

Sleep disorders

The two cases exhibiting sleep disorder were cases of night terror disorder and sleepwalking disorder. Both were disturbances falling within the category of parasomnia, and no cases exhibiting insomnia were seen.

Bipolar disorder

The one case exhibiting bipolar disorder was a boy with mild mental retardation who became symptomatic with depression in 5th grade. Administration of antidepressant medication led to transition to a mixed manic depressive state, which stabilized with the use of carbamazepine. The subject was in a state of remission at the time of the survey.

There were no cases of major depressive disorder. The other depressive disorders with milder symptoms (e.g. dysthymic disorder), which are often unnoticed by the parents or overlooked given the limitation in expressive capacity of children, were excluded from evaluation in the present study due to difficulty in establishing the exact figures.

School refusal

School refusal was noted in eight cases (10%; seven boys, one girl). Time of onset was elementary school (age 6–10 years) in seven, and junior high school (age 12 years) in one case. School refusal was seen in all cases during the course of treatment at the clinic but all had returned to school by the time of the survey. Reasons for school refusal included clashes with teachers adopting strict teaching principles, avoidance of being teased or bullied by other students, and general anxiety attributable to the anxiety disorder. All patients were able to return to school in a relatively short time following intervention such as moderation in teaching attitude, drug therapy, and academic support.

Epilepsy

Among the five cases of epilepsy, two patients had a history of non-febrile convulsions from infancy to childhood but were not on anticonvulsant medication at the time of the survey, after several years free of seizures.

The remaining three patients were being treated with anticonvulsants prescribed by other medical facilities. One patient had been diagnosed with frontal lobe epilepsy, with complex partial seizures. Exact classifications of the other patients cases with generalized tonic–clonic seizures are unknown.

Comparison of comorbidity in terms of type of ADHD

Breakdown of all 68 cases according to type of ADHD revealed 12 cases as being the predominantly inattentive type (17.6%), 15 cases being the predominantly hyperactive–impulsive type (22.0%), and 41 cases as being the combined type (60.3%).

Of the 68 patients included in the present study, rates of comorbidity by type of ADHD for 63 patients (excluding the five female patients) are given in Table 3. Presence/absence of each disorder according to type of ADHD (excepting disorders noted as 0 cases in Table 3) was tested by Fisher's exact probability test. Results were not significant for any of the disorders. Elimination disorder and school refusal were noted in all ADHD types. Oppositional defiant disorder and CD were not found in the predominantly inattentive type.

Table 3. Rate of comorbidity according to type of ADHD
Comorbid disordersPredominantly inattentive type (n = 12)Predominantly hyperactive–impulsive type (n = 14)Combined type (n = 37)P
n%n%n%
  • P, Fisher's exact probability test results.

  • Predominantly inattentive type vs combined type;

  • predominantly hyperactive–impulsive type vs combined type.

  • ADHD, attention deficit–hyperactivity disorder; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th edn; PTSD, post-traumatic stress disorder; NS, not significant.

Disorders according to DSM-IV
 Elimination disorders3251 7.13 8.10.205 NS
 Oppositional defiant disorder0 00 0513.5
 Generalized anxiety disorder216.70 02 5.40.414 NS
 Tic disorders1 8.30 03 8.10.440 NS
 Conduct disorder0 01 7.11 2.70.406 NS
 Sleep disorders0 01 7.11 2.70.406 NS
 Bipolar disorder0 00 01 2.70.406 NS
 PTSD0 01 7.10 0
Disorders not included in DSM-IV
 School refusal1 8.31 7.1513.51.00 NS
 Epilepsy0 0321.42 5.40.103 NS

Comparison of comorbidity in terms of intelligence level

A comparison was made dividing the 63 male patients into a mentally delayed group consisting of 20 patients with IQ < 85 (including seven patients with mental retardation with IQ < 70, and 13 borderline intelligence patients with IQ > 70 but <85), and a normal intelligence group consisting of the other 43 patients. Table 4 shows the presence/absence of comorbidity according in terms of this grouping. No statistical difference was noted between groups by the χ2 test.

Table 4. Presence/absence of comorbidity in terms of intelligence level (63 male patients)
ComorbidityMentally delayed group (IQ < 85, n = 20)Normal intelligence group (IQ ≥ 85, n = 43)Total
  1. χ2 test result was not significant (χ2(1) = 0.0125).

None112334
Present 92029
Total204363

A comparison of comorbidity according to group is shown in Table 5. The presence/absence of each disorder according to group was tested by Fisher's exact probability test. No significant difference was noted for any of the disorders. Testing was not done for CD, sleep disorder, bipolar disorder, and PTSD, for which the number of cases was 0 for one of the two groups.

Table 5. Rate of comorbidity according to intelligence level
 Mentally delayed groupNormal intelligence groupP
(IQ < 85, n = 20)(IQ ≥ 85, n = 43)
n%n%
  1. P, Fisher's exact probability test results.

  2. DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th edn; PTSD, post-traumatic stress disorder; NS, not significant.

Disorders according to DSM-IV
 Elimination disorders210.0511.60.057 NS
 Oppositional defiant disorder1 5.04 9.30.351 NS
 Generalized anxiety disorder210.02 4.70.288 NS
 Tic disorders210.02 4.70.288 NS
 Conduct disorder0 0.02 4.7
 Sleep disorders0 0.02 4.7
 Bipolar disorder1 5.00 0.0
 PTSD0 0.01 2.3
Disorders not included in DSM-IV
 School refusal210.0511.60.330 NS
 Epilepsy210.02 4.70.288 NS

Of the five female patients, three cases were found to be of mental retardation and the other two were normal intelligence cases.

Other

Chief complaint at first visit

Forty-nine patients (72.1%) presented with restlessness, scattering of attention, impulsivity, and other such complaints associated with ADHD. Eight patients (11.8%) expressed complaints associated with comorbid disorders such as school refusal, enuresis, and antisocial behavior, and the other patients presented with academic difficulties, unstable affect, delay in development, and problems with interpersonal relationship as their chief complaints.

Drug therapy

Methylphenidate was prescribed in 46 of 68 cases (68%); one patient was treated with haloperidol, one patient was treated by carbamazepine and the other patients were followed with counseling for the family or the patient without the use of drugs.

In Japan, methylphenidate is currently not certified for use as a therapeutic agent for ADHD, despite its wide use in the USA and established efficacy. For this reason methylphenidate was administered given full informed consent only in patients for whom improvement could not be hoped with intervention other than methylphenidate, and for whom significant improvement in the quality of the child's life could be expected with its use.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

The first point we would like to discuss is how we regarded mental retardation in the present study. The DSM-IV instructs that in children with mental retardation, the additional diagnosis of ADHD should be given only when the symptoms of inattention or hyperactivity are present to degrees in excess of the mental age of the child.9 However, there are no criteria for evaluating developmental inappropriateness in terms of mental age.3 Some investigators consider it sufficient to establish deviation in terms of chronological age-appropriate behavior without special consideration to mental age.3,10 Given this difficulty in determining developmental inappropriateness, we have opted to exclude patients under the mental age of 4, and patients of moderate to severe mental retardation with IQ < 50. We believe it remarkable that even so, cases of mental retardation and borderline intelligence together amounted to 34% (20 boys and three girls) of the present subjects. Despite the clinical significance of concomitant delay in mental development, we are aware of no reports dealing with the proportion of ADHD patients with mental retardation or borderline intelligence. This finding indicates the necessity of incorporating intelligence tests in ADHD diagnosis for evaluating whether the patient's maladaptive behavior or symptoms arise not only from ADHD but from mental delay as well, and providing support as appropriate.

Elimination disorders have been reported as a condition often co-occurring with ADHD,11 which was also found as a comorbid disorder appearing at a high rate in the present study.

Studies to date have demonstrated ODD as being noted in >50% of cases of ADHD.3,12 Although the exact figure is unspecified, Saito indicates a close to 50% rate of comorbidity with this disorder in a Japanese sample.5 Furthermore, when Harada et al. examined the clinical characteristics of cases of ADHD with ODD, they found that compared to cases of either ADHD or ODD alone, the comorbid patients are prone to manifesting relationship difficulties within peer groups, and that strong tendencies for depression and anxiety provide a ready basis for school refusal.6 Regarding CD, which is notable for its high rate of comorbidity with ADHD, severe psychopathology and more serious prognosis,12 family studies and treatment studies support the hypothesis that ADHD comorbid with CD constitutes a nosologically distinct subform within ADHD.13,14 However, we could not extract clinical characteristics related to ODD or CD in our sample because their number was small.

Four out of five of the anxiety disorders noted were generalized anxiety disorder cases, which may be a typical representation of ADHD comorbid with anxiety disorder.15 All four patients were regarded as children with a timid character in whom the tendency of easily becoming anxious had carried over from infancy, rather than anxiety arising secondary to the ADHD.

Regarding the sleeping disorders, in a review of sleep in association with ADHD, Corkum et al. indicate that although a scattering of reports on disturbances in initiating or maintaining sleep are seen, that there is paucity of objective data such as polygraph recordings backing up such reports, and they cite no mention of comorbidity with the parasomnias.16 In the present study, the sleep disorders that appear likely to co-occur with ADHD were the parasomnias such as night terror or sleepwalking, and no cases with complaints of insomnia were encountered.

Regarding comorbidity of ADHD with bipolar disorder, Biederman et al. report 30 cases (23%) among a group of 140 ADHD children followed over 4 years.17 They are reported as being mostly irritable and mixed. The only case encountered in our study was the one patient (1.5%) displaying mixed episodes.

Reports on the incidence of comorbidity with obsessive-compulsive disorder appear to vary at between 4 and 12%.3 The only patient exhibiting obsessive symptoms in the present study was the one with Tourette's disorder, in which the symptom was regarded as being strongly associated with Tourette's disorder rather than ADHD.18 Contrary to our findings, Enokido reported a high prevalence of cases comorbid with obsessive–compulsive symptoms.4 However, her study includes some cases that may be problematic in terms of differentiation between ADHD and pervasive developmental disorder, and it is believed the inclusion of such cases may be contributing to her high reported rate of comorbidity with obsessive–compulsive symptoms.

The school refusal found primarily among elementary school children is believed to be a representative demonstration of maladaptation in school-age children. Causes were clashes with teachers adopting strict teaching principles, poor academic performance, and bullying. All patients returned to school relatively smoothly given individually tailored academic support, and environmental adjustments such as moderation in teaching attitudes, in addition to drug therapy. This is believed to be a characteristic of school refusal co-occurring with ADHD.

The figures obtained in our survey were all consistently and considerably low in contrast to conventional studies primarily from the USA reporting high rates of comorbidity. A primary factor giving rise to this discrepancy may be that the majority (87%) of our subjects were in late infancy to childhood compared to most studies overseas, which focus on cases in childhood to adolescence. However, Wilens et al. note from their study on preschool ADHD cases that mood disorders, anxiety disorders, ODD, and CD were all noted at rates comparable to school-age cases, indicating that lower age does not necessarily mean lower rates of comorbidity.19 As a second consideration, whereas many reports dealing with comorbidity to date have excluded cases of mental retardation, the present report included cases of mild mental retardation. However, analysis of the present mentally delayed group in comparison to the normal intelligence group revealed no statistically significant difference regarding rate of comorbidity, and there was nothing to indicate any qualitative difference between the two groups. Therefore, we believe it questionable as to whether this difference may be considered a factor contributing to the present low rate of comorbidity. The other consideration explaining the disparity is a bias in our sample toward mild cases because Toyota-city Child Development Center is an outpatient clinic without inpatient facilities, which would account for severe cases such as CD requiring hospitalization not being brought to our attention.

Data regarding chief complaints at first visit, and use of drug therapy were included in the present report in order to clarify the characteristic of our subjects and with consideration to their value as reference in presenting the state of ADHD treatment in Japan.

The results obtained have limitations given the small number of cases; that the data were obtained from a clinical setting and not from research conducted on an epidemiological basis; and that they do not include examination of mild cases of mood disorders. However, it is the first comprehensive report on ADHD cases in Japan, which we believe can serve as valid reference demonstrating the actual picture of ADHD in our country. For comparison with reports from the USA and other countries, we believe further study is necessary, increasing the number of cases, and adjusting subject selection to allow for valid comparison.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES
  • 1
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    Barkley RA. Attention Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment, 2nd edn. Guilford Press, New York, 1998.
  • 4
    Enokido F. Clinical studies of attention deficit hyperactivity disorder (ADHD) II: Relation to obsessive–compulsive disorders accompanying ADHD. Jpn J. Child Adolesc. Psychiatry 1999; 40: 386401 (in Japanese).
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    Saito K. AD/HD and affect disorders. Jpn J. Psychiatr. Treat. 2002; 17: 163170 (in Japanese).
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    Harada Y, Yamazaki T, Saitoh K. Psychosocial problems in attention-deficit hyperactivity disorder with oppositional defiant disorder. Psychiatry Clin. Neurosci. 2002; 56: 365369.
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    Jensen P, Martin D, Cantwell D. Comorbidity in ADHD. Implications for research, practice, and DSM-IV. J. Am. Acad. Child Adolesc. Psychiatry 1997; 36: 10651079.
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    Elliot JG. Practitioner review: School refusal: issues of conceptualization, assessment, and treatment. J. Child Psychol. Psychiatry 1999; 40: 10011012.
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  • 11
    Bailey JN, Ornitz EM, Gehricke JG et al. Transmission of primary nocturnal enuresis and attention deficit hyperactivity disorder. Acta Paediatr. 1999; 88: 13641368.
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    Biederman J, Faraone S, Milberger S et al. Is childhood oppositional defiant disorder a precursor to adolescent conduct disorder? Findings from a four-year follow-up study of children with ADHD. J. Am. Acad. Child Adolesc. Psychiatry 1996; 35: 11931204.
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    Faraone S, Biederman J, Mennin D et al. Familial subtypes of attention deficit hyperactivity disorder: A 4-year follow-up study of children from antisocial-ADHD families. J. Child Psychol. Psychiatry 1998; 39: 10451053.
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    Jensen P, Hinshaw SP, Kraemer HC et al. ADHD comorbidity findings from the MTA study: Comparing comorbid subgroups. J. Am. Acad. Child Adolesc. Psychiatry 2001; 40: 147158.
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    Pliszka S. Comorbidity of attention-deficit/hyperactivity disorder with psychiatric disorder: An overview. J. Clin. Psychiatry 1998; 59 (Suppl.): 5058.
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    Corkum P, Tannock R, Moldofsky H. Sleep disturbances in children with attention-deficit/hyperactivity disorder. J. Am. Acad. Child Adolesc. Psychiatry 1998; 37: 637646.
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    Biederman J, Faraone S, Mick E et al. Attention-deficit hyperactivity disorder and juvenile mania: An overlooked comorbidity? J. Am. Acad. Child Adolesc. Psychiatry 1996; 35: 9971008.
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    Spencer T, Biederman J, Harding M et al. Disentangling the overlap between Tourette's disorder and ADHD. J. Child Psychol. Psychiatry 1998; 39: 10371044.
  • 19
    Wilens T, Biederman J, Brown S et al. Psychiatric comorbidity and functioning in clinically referred preschool children and school-age youths with ADHD. J. Am. Acad. Child Adolesc. Psychiatry 2002; 41: 262268.