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Research Article                                                                                                                                        Open Access

## Impairment in Young Preschool Children with Symptoms of AttentionDeficit/Hyperactivity Disorder and Co-occurring Oppositional Defiant Disorder and Conduct Disorder

Bothild Bendiksen 1* , Heidi Aase 2 , Elisabeth Svensson 3 , Svein Friis 1 , Anne Margrethe Myhre 1 , Ted Reichborn-Kjennerud 2 , Pål Zeiner 1

1 University of Oslo, Oslo University Hospital, Department of Psychiatric Research and Development, Norway 2 The Norwegian Institute of Public Health, Division of Mental Health, Norway 3 Department of Clinical Epidemiology, University of Aarhus, Denmark, Norway

*Corresponding author: uxbobe@ous-hf.no

## Abstract

Background: We have limited knowledge of the impact of attention-deficit/hyperactivity disorder (ADHD) symptoms on the daily functioning of young preschool children.

Objective: This study investigated the level of impairment related to symptoms of ADHD in different functional domains. It also addressed how impairment caused by ADHD was related to ADHD subtype, symptom load, gender, and the cooccurrence of oppositional defiant disorder, conduct disorder, or both.

Method: Participating children (N = 807) who were 3.5 years old were recruited from a population-based sample included in The Norwegian Mother and Child Cohort Study. Children who scored above the 90th percentile for ADHD symptoms were included in the present sample. The assessment of the symptoms and functional impairment described in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revision, was based on parental ratings and the semi-structured psychiatric interview entitled 'The Preschool Age Psychiatric Assessment.'

Results: Added burden and discord within family relationships were the areas that were most severely affected. All domain scores were strongly intercorrelated, and they were added to each child's total score. Children with symptoms of ADHD, inattentive type (mean [M], 3.5; standard deviation [SD], 3.4), or ADHD, hyperactive/impulsive type (M, 2.9; SD, 2.7), were significantly  less  impaired  than  children  with  symptoms  of  ADHD,  combined  type  (M  =  6.4;  SD  =  3.8; p <  .001). Furthermore, co-occurring  oppositional  defiant  disorder  was  associated  with  higher  impairment  scores  (M,  6.1;  SD,  4.3) than ADHD alone (M, 3.2; SD, 2.9; p < .001. About 30% of the variance of impairment score of ADHD was explained by symptoms  of  ADHD  and  co-occurring  symptoms  of  oppositional  defiant  disorder  and  conduct  disorder.  Few  gender differences were observed.

Conclusion: Overall, these non-referred young children with clinical symptoms of ADHD were only modestly impaired. Impairment related to ADHD occurred mainly in the areas of family functioning, and it was associated with ADHD subtype and  comorbidity.  Still,  it  is  important  to  assess  the  impact  of  ADHD  symptoms  and  coexisting  difficulties  among preschoolers to identify children and families who are in need of early intervention efforts.

Keywords: impairment,  preschool  children,  parent  ratings,  attention-deficit/hyperactivity  disorder,  oppositional  defiant disorder, conduct disorder, subtype, gender differences

## Introduction

Impairment  in  social,  academic,  or  occupational functioning is a required criterion (criterion D) for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revision (DSM-IV-TR), diagnosis of attention-deficit/hyperactivity disorder (ADHD) (1). The early identification of ADHD has been an important priority area for the last decade; however, the diagnosis of ADHD may be difficult to establish in  children  younger  than  4  to  5  years  old  (1).

Clinically based preschool studies have found children who fulfill ADHD  symptom criteria (criterion  A)  to  have  disturbed  social  relationships, impaired academic achievement, and low selfesteem  (2-4).  In  most  preschool  studies,  similar functional areas of impairment to those assessed in older  children  were  applied;  however,  these  areas may  in  fact  not  be  age-appropriate  with  regard  to context and requirements for young preschool children.

In  a  large  clinical  sample,  Egger  and  colleagues found  that  children  with  ADHD  were  eight  times more  likely  to  be  impaired  than  those  without ADHD and that 58% of children who met ADHD symptom criteria were indeed impaired (2,5). Healey and colleagues found moderate to severe impairment  in  54%  of  children  with  symptoms indicative  of  ADHD,  but  they  did  not  determine which domains were the most debilitating (6).

In the study by Eggers and colleagues, according to parental report, preschoolers with  ADHD, combined  type  (ADHD-C),  were  found  to  have twice the impairment level as compared with children  with  ADHD,  hyperactive-impulsive  type (ADHD-HI)  (2).  Likewise,  in  a  community-based sample, 4-year-old preschool children with ADHDC  were  found  by  teachers'  ratings  to  have  more deficient social skills and to more often be receiving special educational services as compared with children with symptoms of either ADHD, inattentive type (ADHD-IA), or ADHD-HI (7). In a  meta-analysis,  Willcutt  and  colleagues  found  that children  with  symptoms  of  either  ADHD-HI  or ADHD-IA were less globally and socially impaired than those with ADHD-C across all age groups (8). However,  this  meta-analysis  included  only  a  few preschool studies, and the existing preschool studies mainly include referred samples. Willcutt and colleagues also concluded that empirical support is stronger  for  a  model  that  replaces  subtypes  with dimensions  that  reflect  the  number  of  inattentive and hyperactive-impulsive symptoms present. Thus, even if some studies indicate only modest correlations between the number of symptoms and impairment (9,10), preschool community-based studies that investigate the relationship between the number  of  ADHD-IA  and  ADHD-HI  symptoms and functional impairment and that look at whether the  effect  of  combined  symptoms  is  additive  or potentiating are indeed warranted.

For  externalizing disorders in particular,  both impairment and symptoms have been found to be important  for  both  nosology  and  prognosis  (11). Comorbid behavioral disorders -namely oppositional  defiant  disorder  (ODD)  and  conduct disorder  (CD)  -  have  been  found  to  be  strongly associated  with  elevated  levels  of  impairment  in both  school-aged  children  with  ADHD  (8;12-16) and preschoolers with ADHD (4,5,17,18). In most preschool samples,  ODD  and  CD  have  been merged into one disruptive disorder construct when examining the impact of the comorbidity of ADHD (18-20). However, longitudinal studies have suggested that children with ADHD  and  cooccurring ODD may have a different developmental course than those with co-occurring CD  (21-24). Moreover, although the long-term outcomes  of  ODD  are  linked  to  disturbed  social relationships, ADHD and CD predict rule violation, aggression, and poorer academic attainment as compared  with  ODD  (25).  We  have  previously reported that, among  3-year old children with ADHD, co-occurring CD was more strongly related to  ADHD-C  and  ADHD-IA  symptoms  than  cooccurring ODD was (26). With this in mind, we are seeking more information about the possible differences in impact on functioning of cooccurring  ODD  and  CD  in  young  children  with ADHD.

Both a community-based study (19) and a clinically  based  preschool  study  (27)  have  found minor gender differences in globally measured impairment related to ADHD. The study by Healey and  colleagues  found  that  non-referred  boys  were more impaired than non-referred girls according to teachers' reports but not according  to parental ratings  (6).  However,  we  lack  studies  in  this  age group  that  address  potential  gender  differences  in impairment  related  to  ADHD  and  that  look  at whether  subtypes  or  concurrent  ODD  or  CD influence gender differences.

To address these shortcomings, this study investigated  impairment  in  3-year-old  non-referred children who presented with symptoms of ADHD, both  below  and  above  the  diagnostic  threshold. More specifically, we wanted to examine how scores for impairment may vary across functional domains, whether the level of impairment is differently affected  by  symptoms within  the  different  ADHD subtypes, and how co-occurring symptoms of ODD,  CD,  or  both may affect the level of impairment. Furthermore, we wanted to investigate to  what  degree  symptoms  of  ADHD-IA,  ADHDHI, ODD, and CD predicted the level of impairment. Lastly, we wanted to examine whether there were gender differences in impairment related to ADHD.

## Materials and methods

Participants

All participants were recruited from the Norwegian Mother and Child Cohort Study (MoBa), a popula- tion-based prospective birth cohort study of about 107,000 children conducted by the Norwegian Institute  of  Public  Health  (28).  To  identify  a  large number  of  preschoolers  who  might  be  at  risk  for developing ADHD, 3-year-old children whose sum score  was  higher  than  the  90th  percentile  for  11 questions  related  to  hyperactivity,  impulsivity,  and inattention  for  the  36-month  MoBa  questionnaire were invited to a clinical assessment; 6 of these 11 questions  were  selected  from  the  Child  Behavior Checklist  (29),  and  5  questions  were  from  the symptom criteria for ADHD in DSM-IV-TR (1). Of the 2,798 invited children, 1,048 (37.5%) completed the  clinical  assessments,  including  the  diagnostic evaluation.  Enrollment  in  the  present  part  of  the preschool  ADHD  study  was  described  in  further detail in a previous publication (26). There were no statistically significant differences between participants and invited non-participants with regard to  background  factors  (i.e.,  parental  marital  status, parental educational level, parental age) except for a higher maternal educational level among participants.  Participants  in  the  present  study  were 807 children who had one or  more  ADHD symptoms and available data regarding their ADHD impairment score.

The  children,  who  were  between  the  ages  of  36 and  44  months,  participated  in  a  1-day  clinical assessment  at  Oslo  University  Hospital  together with  at  least  one  parent.  The  clinical  assessment included neuropsychological and neuromotor evaluations  in  addition  to  a  clinical  interview  to assess psychiatric symptoms. The exclusion criteria were  severe  medical  conditions  or  high  scores  for autistic symptoms. One of the parents had to speak the Norwegian language.

## Symptom measures

One  of the parents, usually the mother, was interviewed with a semi-structured interview entitled 'The Preschool Age Psychiatric Assessment'  (PAPA)  (30).  The  PAPA  includes questions about psychiatric symptoms as they related  to  preschool-aged  children,  including  their frequency, intensity, cross-situationality,  and  age  of onset.  The  PAPA  interviews  were  performed  by trained  psychology  students  and  supervised  by  a clinically  trained  psychologist  or  child  psychiatrist, with high inter-rater reliability (26). All 18 diagnostic symptom  criteria  for  ADHD  were  discussed.  The eight  DSM-IV-TR  diagnostic  symptom  criteria  for ODD were modified by cutpoints for the frequency level  of  symptoms  and  reflect  the  top  10%  of frequency for preschool children (31). Eight of the 15  DSM-IV-TR  diagnostic  symptom  criteria  that had  previously  been  found  applicable  for  CD  in preschool-aged  children  were  used  for  diagnostic decision making (31,32).

Symptom  threshold  groups  of  ADHD,  ODD, and CD were generated with the use of algorithms that implemented symptom criteria from criterion A of the DSM-IV-TR (1). The low ADHD symptom group  consisted  of  children  with  one  or  more ADHD  symptoms but who were below the diagnostic threshold of each subtype. On the basis of the diagnostic threshold symptom counts, ADHD only and the co-occurring groups of ODD, CD, or both were created.

## Impairment measures

Each section of the PAPA was concluded with an evaluation of impairment. However, the impairment scores  for  the  separate  diagnoses  were  strongly correlated  with  comorbid  conditions,  co-occurring ADHD  and  ODD  ( r =  0.65),  and  co-occurring ADHD and  CD  ( r =  0.90),  which  points  toward parental ratings reflecting a more global impact than attributing disability to one specific disorder. In this article,  we  therefore  only  use  impairment  reported with ADHD symptoms.

Whenever  a  parent  reported  his  or  her  child exhibiting at least one diagnostic symptom discussed in the PAPA, impairment was scored for six functional domains:

- 1) family (relationships with parents and siblings);
- 2) friends (the ability to make them and keep them);
- 3) learning (the child's learning capacity in structured activities like drawing, doing puzzles, and so on);
- 4)  play  and  leisure  activities  (participation  in  play and showing the normal range of variation);
- 5) quality of life (the interference of symptoms with the child's quality of life);
- 6)  burden  to  family  (the  interference  of  symptoms with family routines and daily life).

Each subscale of impairment was given a score of between 0 and 3, with 0 meaning 'no,' 1 meaning 'yes,  minor  difficulties,'  2  meaning  'yes,  definite difficulties,' and 3 meaning 'yes, severe difficulties.'  The  summed  score  of  all  six  coded functional domains formed a total impairment score with  a  range  of  0  to  18.  With  sufficient  psychometric properties (Cronbach's alpha = 0.83) and the corrected item total correlations between the different subscales and the total impairment score ( r = 0.55-0.65), we used the total impairment score in most subsequent analyses. A sum score of 3 on the total impairment scale was at the 75th percentile for the whole sample and was considered to indicate a moderate level, whereas a score of 5 was at the 90th percentile  and  indicated  a  more  severe  level  of impairment.  Inter-rater  reliability  was  0.94  for  the impairment  score  of  ADHD,  0.85  for  ODD,  and 0.99 for CD.

## Covariates

Covariates included maternal and paternal educational  level,  which  were  obtained  from  the MoBa  questionnaire  at  17  weeks'  gestation.  We lacked information about paternal educational level for 59 children and about maternal educational level for 26 children, but the missing cases were equally distributed  among  the  different  symptom  groups. Information  about  maternal  age  at  delivery  and marital  status  was  obtained  from  the  Norwegian Medical  Birth  Registry  (33).  The  educational  levels of the parents were moderately correlated ( r = 0.57; p <  .001),  and  we  chose  to  use  the  maternal educational  level  as  a  covariate  and  a  measure  of socioeconomic status for our analysis. A measure of the child's general intellectual functioning was obtained as a part of the neuropsychological assessment  with  the  use  of  a  short  form  of  the Stanford-Binet Intelligence Scale, Fifth Edition (34), which was administered by a trained psychologist.

## Ethics

The  study  was  approved  by  the  Regional  Ethics Committee,  and a license was granted by the Norwegian Data Inspectorate in 2007. Assessments were carried out in accordance with ethical standards, and the principles of the  Declaration of Helsinki were followed. Parents returned their written consent before the clinical assessment took place.

## Statistical Analysis

We  assessed the frequencies of the covariates among children with low ADHD symptoms and for groups with ADHD, ADHD+ODD, ADHD+CD, and ADHD+ODD+CD symptoms above threshold.  For  group  comparisons,  we  used  oneway  analysis  of  variance  for  continuous  measures and a chi-squared test for independence for categorical data.

One-way between-group analysis of variance with Bonferroni  correction  for  post-hoc  comparisons was conducted to investigate the impact of subtype and  co-occurrence  of  ODD,  CD,  or  both  on  the level of impairment related to ADHD.

We further examined the relationship between the number  of  symptoms  and  the  impairment  score with the use of the Pearson product-moment correlation and the ability of the number of ADHD-IA, ADHD-HI, ODD, and CD symptoms to  predict  the  level  of  total  impairment  score  of ADHD by multiple  linear  regression  analyses  that were  controlled  for  covariates  (i.e.,  maternal  and paternal  educational  level,  child's  intelligence  level and  gender).  We  tested  for  statistical  interactions between  ODD  and  CD  and  between  gender  and ODD/CD in step 2; we looked for these between combined  ADHD-HI  and  ADHD-IA  symptoms and between gender and ADHD-HI/ADHD-IA in step 3. To avoid collinearity and to facilitate interpretation,  continuous  variables  were  centered into z-scores before interaction terms were created (35).

Lastly,  we  examined  gender  differences  in  the total  impairment  score  of  ADHD  according  to symptom subtypes and co-occurring symptom clusters  of  ODD,  CD,  or  both  with  the  use  of crosstabs, chi-squared tests, and independentsample t -tests.

PASW  Statistics 18 was used for statistical analyses. All tests were two-tailed.

## Results

Sample characteristics are presented in Table 1. Of the 807 children included, 73% (n = 593) had low ADHD  symptoms;  their  symptom  counts  were between one and six  for  the  ADHD-HI  and ADHD-IA groups and between one and ten for the ADHD-C  group.  ADHD  symptoms  above  the diagnostic  threshold  were  present  in  27%  of  the group (n = 214): 6% (n = 12) had ADHD-IA, 76% (n  =  163)  had  ADHD-HI, and 18% (n = 39) had ADHD-C. Of the 214 children with ADHD, 63% (n = 135) had symptoms of ADHD only, whereas 37% (n = 79) had co-occurring symptoms of ODD, CD, or both.

Of  children  with  threshold  ADHD  symptoms, 43% had impairment scores of less than 3, 24% had scores  of  3  or  4  (i.e.,  between  the  75th   and  90th percentiles), and 33% had scores of 5 or more (i.e., at the 90th percentile or above); this was indicative of moderate to severe levels of impairment in 57% of these children.

Figure 1 shows the assessed functional areas and the  percentage  of  children  below  and  above  the threshold for ADHD who had moderate or severe levels  of  impairment.  Only  0%  to  2%  of  children with symptoms  below  diagnostic  the  level  was moderate or severely impaired in the areas of play, friends, and learning; this was compared with 8% to 13% of children who had a symptom load that was at  or  above  the  diagnostic  threshold.  Of  children with threshold ADHD  symptoms, 24% were reported to have disturbed family relationships, and 32%  displayed  behaviors  that  were  perceived  as burdens to their families; for those children whose symptoms  were  below  threshold,  these  numbers were 5% and 9%, respectively.

TABLE 1. Sample characteristics of 807 preschool children

| Below/above DSM-IV diagnostic symptom level   |       |       | Below             |                   | Above     |           | Above      |            | Above          |                | Above      |
|-----------------------------------------------|-------|-------|-------------------|-------------------|-----------|-----------|------------|------------|----------------|----------------|------------|
|                                               | Total | Total | Low ADHD symptoms | Low ADHD symptoms | ADHD only | ADHD only | ADHD + ODD | ADHD + ODD | ADHD + CD ADHD | ADHD + CD ADHD | + ODD + CD |
| N                                             | 807   | 807   | 593               | 593               | 135       | 135       | 43         | 43         | 17             | 17             | 19         |
|                                               | N     | %     | N                 | %                 | N         | %         | N          | % N        | %              | N              | %          |
| Gender (boys)                                 | 436   | 54    | 313               | 52.8              | 83        | 61.5      | 23         | 53.5 11    | 64.7           | 6              | 31.6       |
|                                               | M     | SD    | M                 | SD                | M         | SD        | M          | SD M       | SD             | M              | SD         |
| Age (months)                                  | 41.8  | 1.3   | 41.8              | 1.3               | 41.7      | 1.3       | 41.6       | 1.3 41.4   | 1.3            | 41.9           | 1.4        |
| Intelligence quotient                         | 101.6 | 9.2   | 102.2             | 9.3               | 100.3     | 9.1       | 101.9      | 8.2 98.1   | 8.4            | 97.3           | 9.6        |
| IA symptoms*                                  | 1.8   | 1.9   | 1.2               | 1.3               | 3.3       | 2.2       | 3.7        | 2.3 3.8    | 2.6            | 4.2            | 2.9        |
| HI symptoms*                                  | 3.7   | 2.3   | 2.6               | 1.5               | 6.5       | 1.3       | 7.1        | 1.1 6.5    | 1.8            | 7.2            | 0.9        |
| ODD symptoms*                                 | 1.9   | 1.6   | 1.7               | 1.5               | 1.6       | 1.1       | 4.8        | 0.9 1.9    | 0.9            | 5.2            | 1.3        |
| CD symptoms*                                  | 0.8   | 1.1   | 0.6               | 0.9               | 0.8       | 0.8       | 0.9        | 0.9 3.5    | 0.7            | 3.7            | 0.9        |
| Mother's age (years)                          | 30.3  | 4.2   | 30.6              | 4.2               | 29.8      | 4.4       | 30.1       | 4.3 30.6   | 3.8            | 28.1           | 3.4        |
| Mother's education (years)                    | 15.1  | 2.4   | 15.4              | 2.3               | 14.6      | 2.5       | 14.4       | 2.1 14.3   | 2.6            | 14.0           | 2.5        |
| Father's education (years)                    | 14.4  | 2.8   | 14.6              | 2.7               | 13.9      | 2.9       | 13.5       | 2.7 13.1   | 2.4            | 13.6           | 2.8        |
|                                               | N     | %     | N                 | %                 | N         | %         | N          | % N        | %              | N              | %          |
| Civil status (single parents)                 | 31    | 3.6   | 15                | 2.5               | 10        | 7.4       | 2          | 4.7 1      | 5.9            | 1              | 5.3        |

Low ADHD symptoms, The presence of at least one symptom of attention-deficit/hyperactivity disorder (ADHD), but the number of symptoms is below the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revision, diagnostic threshold level; ADHD only, ADHD alone; ADHD + ODD, co-occurrence of ADHD and oppositional defiant disorder (ODD); ADHD + CD, co-occurrence of ADHD and conduct disorder (CD); ADHD + ODD + CD, co-occurrence of ADHD, ODD, and CD; IA symptoms, symptoms of ADHD, inattentive type; HI symptoms, symptoms of ADHD, hyperactive-impulsive type; ODD symptoms, symptoms of oppositional defiant disorder; CD symptoms, symptoms of conduct disorder.

FIGURE 1 . Percentage of children with attention-deficit/hyperactivity disorder symptoms below and above the diagnostic threshold for moderate to severe impairment in various functional domains.

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Note: fam.burden, burden on the family; rel.fam, the relationship between the parent (family) and the child; lifequal., quality of the child's life; learning, the ability to learn in various settings and through activities such as reading and doing puzzles; play, the ability to engage in play within a normal range of variation; friends, the ability to get and keep friends.

Low ADHD symptoms: the presence of at least one symptom of attentiondeficit/hyperactivity disorder, but the number of symptoms is below the diagnostic threshold level.

ADHD threshold symptoms: attention-deficit/hyperactivity disorder symptom counts above the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revision, diagnostic threshold level.

Figure  2  shows  impairment  scores  of  ADHD according to subtypes. Children with ADHD-C had significantly  higher  impairment  scores  (mean  [M], 6.4; standard deviation [SD], 3.8) than children with either  ADHD-HI  (M,  3.5;  SD,  3.4)  or  ADHD-IA (M, 2.9; SD, 2.7; Welch statistics [3, 41.7], 37.8; p < .001). Scores of more than 3 were present in 90% of children with ADHD-C symptoms.

FIGURE 2. IMPAIRMENT SCORE related to attention-deficit/hyperactivity disorder ACCORDING TO attention-deficit/hyperactivity disorder SUBTYPE

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Note:  Low  ADHD  symptoms, Attention-deficit/hyperactivity  disorder  (ADHD) symptom counts  between 1 and  6  (or  of  up  to  10  for  ADHD-C  symptoms); ADHD-IA, ADHD, inattentive type (symptom counts of 6 or more); ADHD-HI, ADHD, hyperactive-impulsive type (symptom counts of 6 or more); ADHD-C, ADHD, combined type (symptom counts of 12 or more).

Each child's impairment score related to ADHD was  moderately  correlated  with  the  number  of ADHD  symptoms  ( r =  0.54; p <  .001),  ODD symptoms ( r = 0.30; p < .001), and CD symptoms ( r =  .26; p <  .001).  An  exploratory  analysis  revealed that  the  total  impairment  score  gradually  increased with  an  increasing  number  of  ADHD  symptoms both below and above threshold level and with no distinct  breaking  point  at  any  level  of  impairment that was indicative of the diagnostic threshold.

The  relationship  between  the  total  impairment score related to ADHD  and  the number of symptoms  was  further  examined  with  hierarchical multiple  regression  analysis  (Table  2).  Background characteristics were entered at step 1 and explained 2%  of the variance in impairment related to ADHD. The numbers of ODD and CD symptoms were  entered  at  step  2,  and  the  explained  variance was  13%  ( F [6,  764]  =  18.2; p <  .001;  R-squared change = 0.10; F change [3, 764] = 29.3; p < .001). Numbers of ADHD-IA and ADHD-HI symptoms were entered at step 3, and total variance explained by the model was 32% ( F [9, 761] = 39.4; p < .001; R-squared change = 0.19, F change [3, 761] = 71.6, p <  .001).  In  the  final  model,  there  was  a  positive interaction  between  gender  and  the  number  of ODD  symptoms. In addition, the interaction between  the  numbers  of  ADHD-IA  and  ADHDHI symptoms added a statistically significant contribution to the explained variance of the impairment  score  of  ADHD,  which  indicated  a multiplicative effect of combined symptoms.

TABLE 2. The associations between the number of symptoms of attention-deficit/hyperactivity disorder, inattentive type; attentiondeficit/hyperactivity disorder, hyperactive-impulsive type; oppositional defiant disorder, and conduct disorder to the impairment score related to attention-deficit/hyperactivity

## Impairment score related to attention-deficit/hyperactivity disorder

|                       | Step   | Step   | Step   | Step   | Step   | Step   | Step   | Step   | Step 3   | Step 3   | Step 3   | Step 3   |
|-----------------------|--------|--------|--------|--------|--------|--------|--------|--------|----------|----------|----------|----------|
|                       | B      | SE B   |       | P      | B      | SE B   |       | P      | B        | SE B     |         | P        |
|                       | 5. 99  | 1.15   |        | .000   | 3.83   | 1.13   |        | .001   | .41      | 1.03     |          | .69      |
| Gender (boys)         | .34    | .19    | .06    | .08    | .00    | .28    | .00    | .10    | -.15     | .16      | -.03     | .54      |
| Intelligence quotient | -.03   | .01    | -.09   | .01    | -.02   | .01    | -.06   | .07    | -.01     | .01      | -.03     | .35      |
| Mother's education    | -.10   | .04    | -.09   | .01    | -.06   | .04    | -.06   | .11    | .01      | .03      | .01      | .70      |
| ODD symptoms*         |        |        |        |        | .25    | .08    | .15    | .002   | .09      | .07      | .05      | .25      |
| ODD/boys              |        |        |        |        | .34    | .18    | .09    | .06    | .34      | .16      | .09      | .03      |
| CD symptoms*          |        |        |        |        | .42    | .09    | .17    | .000   | .16      | .08      | .06      | .06      |
| IA symptoms*†         |        |        |        |        |        |        |        |        | .29      | .05      | .21      | .000     |
| HI symptoms*†         |        |        |        |        |        |        |        |        | .35      | .04      | .31      | .000     |
| IA/HI*†               |        |        |        |        |        |        |        |        | .16      | .08      | .07      | .05      |

ODD symptoms, The number of symptoms of oppositional defiant disorder (ODD); ODD/boys, interactions of male gender and the number of ODD symptoms; CD symptoms, the number of symptoms of conduct disorder; IA symptoms, the number of symptoms of attention-deficit/hyperactivity disorder (ADHD), inattentive type; HI symptoms, the number of symptoms of ADHD, hyperactive-impulsive type; IA/HI, interactions of the number of symptoms of ADHD, inattentive type, and ADHD, hyperactive-impulsive type.

B, the value of the unstandardized regression coefficient; SE B, the standard error;  , the value of the standardized regression coefficient.

Moderate  or severe levels of  impairment  were present in 81% of children with co-occurring ODD as compared to 53% of children with co-occurring CD and 58% of  children  with  a  co-occurrence  of both  ODD  and  CD.  There  were  some  significant differences in the impairment scores between groups  of  children  with  ADHD  and  co-occurring ODD,  CD,  or  both  (Welch  statistics  [4,  54.8]  = 25.9; p <  .001)  (Figure  3).  Post-hoc  comparisons indicated that children with ADHD  and cooccurring ODD  (M,  6.1;  SD,  4.3) were  more impaired than children with low ADHD symptoms (M, 1.4; SD, 1.9) and children with ADHD only (M, 3.2; SD, 2.9). Children with ADHD only, those with ADHD and co-occurring CD,  and  those  with  cooccurring  symptoms  of  both  ODD  and  CD  were not  significantly  different  from  each  other,  but  all groups were significantly more impaired than children with low ADHD symptoms.

FIGURE 3. Impairment score related to attention-deficit/hyperactivity disorder in  children  with  attention-deficit/hyperactivity  disorder  alone  and  in  those with co-occurring oppositional defiant disorder, conduct disorder, or both.

<!-- image -->

More  boys  than  girls  had  impairment  scores  of more  than  5  (i.e.,  more  than  the  90th  percentile): 69% of boys (n = 48) versus 31% of girls (n = 22) ( χ 2 =  5.2; p =  .02).  Boys  with  co-occurring  ODD

had  higher  impairment  scores  than  girls  ([M,  7.5; SD, 5.0] versus ([M, 4.4; SD, 2.3]; t [32.2] = 2.7; p = .01).

## Discussion

In  this  population-based  sample  of  non-referred preschool  children  with  high  screening  scores  for characteristics  of  ADHD,  the  strongest  impact  of ADHD symptoms was seen in the areas of family functioning, creating discord within family relationships and putting an added burden on families.  Only  33%  of  preschoolers  with  clinical ADHD  symptoms  were  rated  as  impaired  at  a conservative cutoff, and less than 60% were considered impaired when a more liberal cutoff was used.  Children  who  fulfilled  diagnostic  symptom criteria were rated almost three times as impaired as children with symptom counts below the diagnostic level, and children with ADHD-C turned out to be almost twice as impaired as those with ADHD-IA or ADHD-HI. Among children within co-occurring symptoms, those with co-occurring ODD were the most debilitated. A positive linear relationship between  impairment  score and the  number  of ADHD symptoms was demonstrated, but there was no distinct breaking point at any level of impairment to indicate a diagnostic threshold. The number  of  ADHD  symptoms  explained  less  than 30%  of  the  variance  in  the  impairment  score  of ADHD. More  boys  than  girls  had  severe  level  of impairment, and boys with co-occurring ODD were slightly more impaired than girls. Largely, however, there were only minor gender differences in impairment related to ADHD.

Functional areas like friendship, learning, and play -  which,  in  school-aged  children,  have  been  found to  be  affected  by  ADHD  symptoms  (12;36-38)  were not considerably affected in these  young preschoolers. This probably reflects the more demanding contextual environment of older children as compared with that of 3- and 4-year old children.  Thus,  the  further  evaluation  of  which functional domains of impairment should be assessed in preschoolers may be warranted.

In line with previous community-based and clinically based preschool studies, (2,7,39), a considerably larger proportion of children with ADHD-C were reported to be significantly impaired,  and  they  were  found  to  have  twice  the impairment levels of children with either ADHD-IA or ADHD-HI. Children with symptoms of ADHDIA  were  found  to  be  even  less  impaired  than children  with  ADHD-HI  symptoms,  although  no firm conclusions can be drawn because of the small numbers involved in these studies. Clinical levels of inattentiveness seem to represent a rare phenomenon unless they are combined with ADHD-HI symptoms, and several large preschool samples have been unable to identify children with the ADHD-IA subtype (2,18,27,40). Inattentiveness and  its  clinical  significance  seem  to  be  hard  to evaluate in these young preschool children.

We found that children with symptoms of ADHD and co-occurring ODD were more impaired than children with ADHD alone, which is also in line with the findings of previous preschool studies (5,17,20), although neither group significantly  differed  from  the  group  of  children with co-occurring CD.  To  our knowledge, no previous preschool studies have compared the impact of the comorbidity of ODD versus CD. The existing comparisons have focused less on impairment  than  symptom  patterns,  or  the  two diagnostic  categories  of  ODD  and  CD  have  been collapsed  into  one  disruptive  behavior  construct (7;18-20;40,41).  About  80%  of  children  with  cooccurring  ODD  had  moderate  or  severe  levels  of impairment as compared with about 50% of those with co-occurring CD. Given that temper outbursts and  defiance  may  be  considered  as  normative  and age-appropriate in 3- and 4-year-old children, these findings  were  somewhat  surprising.  Alternatively, ODD may be highly context-specific, and it may be one  of  the  few  disorders  with  manifestations  that are  seen  solely  in  the  home  environment.  Thus, parents  probably  shoulder  most  of  the  burden  of the defiance, irritability, or emotional dysregulation problems associated  with  ODD  as  compared  with the  symptoms  of  CD.  The  more  discrete,  covert, and  lower  base-rate  symptoms  of  CD  could  be considered simply as immature and transient behaviors and thus be perceived as less impairing by the parents, especially in these very young children. However, the results cannot be generalized because of the small sample sizes in studies of co-occurring groups with ADHD and CD. These findings require replication.

Previous  studies  of  school-aged  children  have found that ADHD symptoms explain about 25% to 30%  of  variance  in  impairment  (9-11),  which  is quite  similar  to  our  findings  of  less  than  30%.  A pertinent question is of course which other factors determine impairment in children with ADHD, but studies specifically addressing these issues are largely missing. In our  study, gender, intelligence,  and parental  educational  level  did  not  add  much.  We must  assume  that  the  impairment  score  covers several aspects of daily living that go  beyond separate symptom  descriptions. The score will probably also reflect factors such as attitudes toward  parents  and  siblings,  self-esteem,  mood, anxiety,  and  others.  Thus,  it  will  be  expected  that psychiatric  symptoms  will  only  explain  a  smaller proportion of the variance in impairment. However, it  is  also  possible  that  the  answer  to  this  question will in part depend on which functional domains are being scrutinized (10).

Among children  with  symptoms  of  ADHD  and concurrent  ODD,  boys  were  found  to  be  slightly more impaired than girls. Overall, however, gender differences  in  impairment  related  to  ADHD  were negligible.  The  absence  of  gender  differences  in functional  impairment  related  to  ADHD  has  also previously  been  reported  from  community-based samples of both preschoolers and school-aged children (19,42). Conversely, a meta-analysis by Gaub  and Carlson demonstrated  more evident gender differences  in  community-based  samples than in clinical samples (43). Although non-referred school-aged boys with ADHD were more impaired than girls, no differences were found in the clinical samples. Clinical samples may be less suited for the investigation  of  gender  differences,  because  girls with ADHD  are referred for treatment less frequently  than  boys  are  (44).  Thus,  the  effects  of gender on impairment related to ADHD still seem somewhat  ambiguous  (44),  and  direct  comparison across  studies  seems  to  be  a  problem,  because gender  effects will partly hinge  on  the  referral source,  the  rater  source,  the  ages  of  the  children studied, and which functional domains were examined (45).

## Strengths and limitations

The present population-based sample of nonreferred  preschool  children  with  high  scores  on ADHD traits allowed for the study of impairment related  ADHD  in  a  relatively  large  sample.  The children were examined with the use of a validated and  structured  diagnostic  interview  that  included detailed information about present psychiatric symptoms and impairment and that had high internal  consistency  for  impairment  measures.  The considerable number of children with symptoms of ADHD  gave  us  the  opportunity  to  examine  the ADHD  subtypes  separately  and  allowed  for  the examination of potential predictors of impairment. Population-based studies may be particularly pertinent for the detection of predictors of functional impairment at an early stage of development,  because  clinical  samples  are  often subject  to  referral  biases,  with  increased  rates  of comorbidities, a predominance of boys, and greater symptom severity (41,43).

This  study  also  has  limitations.  First,  the  study selection was a two-step process. Participants were initially  enrolled  in  the  MoBa  and  then  into  the present study. Although  the  original cohort of

107,000  was  large  and  recruited  broadly  from  the population,  the response rates  for both  MoBa  and the ADHD  study were low (39% and 37%, respectively).  However,  no  significant  differences between  participants in  MoBa  and  the  general population were found for eight selected exposure/outcome  associations  (e.g.,  smoking  and birth  weight  (47))  or  between  participants  in  the MoBa  and  the ADHD  study,  with  the single exception of higher maternal education in the ADHD study as compared with MoBa. It is likely that  participants  with  the  energy  to  be  involved  in both  of  these  studies  were  highly  well-functioning families.

Second, we lacked information about impairment for 6% of the sample, but there were no differences in background characteristics between children lacking information and children with available impairment ratings.

Third, the impairment scale and the subscales of the different functional areas used in this version of PAPA differ from the original version of the PAPA (30)  in  two  aspects.  For  example,  the  subscale addressing  the  impairment's  burden  to  the  family was  derived  from  the  Strengths  and  Difficulties Questionnaire  (48)  and  added  to  the  impairment scale in the version of the PAPA used this study. In addition, the scale used in this present study includes  a  rating  that  goes  from  0  to  18,  which  is similar  to  the  impairment  score  obtained  with  the Strengths  and  Difficulties  Questionnaire;  however, the original PAPA  scale runs from 0 to 30. However,  the  sum  score  of  impairment  related  to ADHD  in  this  present  study  demonstrated  good psychometric properties.

Fourth,  we  did  not  correct  for  other  variables (e.g., co-occurring disorders) when presenting impairment related to ADHD  in the various functional  domains  (see  Figure  1)  or  according  to subtypes of ADHD (see Figure 2).

Fifth,  both  symptoms  and  impairment  scores were based solely on parents' ratings, and information  from  teachers  would  probably  better reflect  the  true  variance  of  children's  behavior  in structured learning and play settings. Clinical diagnostic  decisions  are  based  on  the  assumptions that  symptoms  and  impairment  are  related  but separate  constructs  (10,38),  and  impairment  could be regarded as an independent external validation of a disorder and as being essential to avoid tautology in which the same measures are used to define and externally  validate  a  disorder  (8). However,  when the same rater evaluates both symptoms and impairment,  this  does  not  necessarily  hold  true, because rater bias may be a problem. Nevertheless, the use of a validated and structured clinical interview provided a wide scope of cross-situational information about symptoms and impairment. Parents'  ratings  have  largely  been  found  to  be reliable  independent  predictors  of  severity  and  of the  diagnosis  of  ADHD  in  preschoolers  at  follow up (49).

When using categorical diagnostic entities, children  in  the  low  ADHD  symptom  group  may have a higher number of combined symptoms than children with threshold symptoms of ADHD-IA or ADHD-HI.  This  problem  has  been  addressed  by previous  studies,  which  have  demonstrated  that children  with  subthreshold  symptoms  of  ADHD might be as impaired as children who fulfill diagnostic symptom  criteria (50, 51).  However, more knowledge is required about whether functional impairment, symptom load, or symptom patterns predict further difficulties in this age group.

These children are too young to receive a formal diagnosis of ADHD,  and  the  use of existing nosology  could  lead  to  both  the  overidentification and  underidentification  of  disorders  in this  age group  (52).  In  addition,  the  predictive  validity  of ADHD, ODD, and CD symptoms has been found to be only moderate for 4-year-old preschool children  (8,32,53),  and  no  studies  have  tested  the predictive validity of CD symptoms for children less than  4.5  years  old.  Thus,  our  knowledge  of  the developmental trajectories of CD symptoms is still limited. There is a need for the further validation of clinical  constructs  and  the  determination  of  the appropriate criteria for CD in particular,  and these are also needed for ADHD and ODD in younger, non-referred preschoolers. Our study requires replication  and  follow  up  to  make  the  distinction between children who will have a persistent symptom pattern and those who will have transient symptoms.

## Clinical significance

The systematic assessment of impairment related to ADHD  is  necessary  for  preschool  children,  and parental  ratings  of  functional  impairment  provide useful  information  about  early  problems  that  arise within  families.  However,  rather  than  being  linked to  specific  settings,  parental  ratings  of  functional impairment probably reflect the more global impact of children's symptoms on daily functioning across several  settings.  Parents'  perception  of  children's behavior as a burden to the family and as contributing to relational difficulties within the family  may  well  indicate  early  emerging  coercive cycles and thereby be an important target for early prevention  and  intervention  strategies.  Thus,  such assessment  is  important  when  identifying  children who are at risk.

Minor  functional  interference  was  reported  in nearly  half  of  children  with  clinical  symptoms  of ADHD,  but  a  major  proportion  of  children  with symptoms of ADHD-C and those with cooccurring  ODD  had  higher  levels  of  impairment, and they should thus likely be monitored over time.

## References

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR®. American Psychiatric Publication, 2000.
2. Egger  HLM,  Kondo  DM,  Angold  AM.  The  epidemiology  and diagnostic Issues  in  preschool  Attention-Deficit/Hyperactivity Disorder: A review. Infants &  Young  Children AttentionDeficit/Hyperactivity Disorder 2006;19(2):109-22.
3. Lahey  BB,  Pelham  WE,  Loney  J,  et  al.  Three-year  predictive validity  of  DSM-IV  attention  deficit  hyperactivity  disorder  in children diagnosed at 4-6 years of age. Am  J Psychiatry 2004;161(11):2014-20.
4. Wilens TE, 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(3):262-8.
5. Egger HL, Angold A.  Common  emotional and behavioral disorders in preschool children: presentation, nosology, and epidemiology. J Child Psychol Psychiatry 2006;47(3-4):313-37.
6. Healey DM, Miller CJ, Castelli KL, Marks DJ, Halperin JM. The impact  of  impairment  criteria  on  rates  of  ADHD  diagnoses  in preschoolers. J Abnorm Child Psychol 2008;36(5):771-8.
7. Nolan EE, Gadow KD, Sprafkin J. Teacher reports of DSM-IV ADHD, ODD, and CD symptoms in schoolchildren. J Am Acad Child Adolesc Psychiatry 2001;40(2):241-9.
8. Willcutt  EG, Nigg JT, Pennington BF, Solanto MV, Rohde LA, Tannock R, et al. Validity of DSM-IV attention deficit/hyperactivity disorder symptom dimensions and subtypes. J Abnorm Psychol 2012;121(4):991-1010.
9. Gathje RA, Lewandowski LJ, Gordon M. The role of impairment in the diagnosis of ADHD. J Atten Disord 2008;11(5):529-37.
10. Gordon  M,  Antshel  K,  Faraone  S,  Barkley  R,  Lewandowski  L, Hudziak  JJ,  et  al.  Symptoms  versus  impairment:  the  case  for respecting DSM-IV's Criterion D. J Atten Disord 2006;9(3):46575.
11. Pickles  A,  Rowe  R,  Simonoff  E,  Foley  D,  Rutter  M,  Silberg  J. Child psychiatric symptoms and psychosocial impairment: relationship and prognostic significance. Br J Psychiatry 2001;179:230-5.
12. Coghill D, Spiel G, Baldursson G, et al. Which factors impact on clinician-rated  impairment  in  children  with  ADHD?  Eur  Child Adolesc Psychiatry 2006;15 Suppl 1:I30-I37.
13. Connor  DF,  Doerfler  LA.  ADHD  with  comorbid  oppositional defiant  disorder  or  conduct  disorder:  discrete  or  nondistinct disruptive behavior disorders? J Atten Disord 2008;12(2):126-34.
14. Kessler  RC,  Adler  LA,  Barkley  R,  Biederman  J,  Conners  CK, Faraone SV, et al. Patterns and predictors of attentiondeficit/hyperactivity  disorder  persistence  into  adulthood:  results from the national comorbidity survey replication. Biol Psychiatry 2005;57(11):1442-51.

15. Newcorn JH, Halperin JM, Jensen PS, Abikoff HB, Arnold LE, Cantwell  DP,  et  al.  Symptom  profiles  in  children  with  ADHD: effects  of  comorbidity  and  gender.  J  Am  Acad  Child  Adolesc Psychiatry 2001;40(2):137-46.
16. Pliszka SR. Comorbidity of attention-deficit/hyperactivity disorder with psychiatric disorder: an overview. J Clin Psychiatry 1998;59 Suppl 7:50-8.
17. Gadow KD, Nolan EE. Differences between preschool children with  ODD,  ADHD,  and  ODD+ADHD  symptoms.  J  Child Psychol Psychiatry 2002;43(2):191-201.
18. Lavigne JV,  Lebailly  SA,  Hopkins  J,  Gouze  KR,  Binns  HJ.  The prevalence  of  ADHD,  ODD,  depression,  and  anxiety  in  a community sample of 4-year-olds. J Clin Child  Adolesc  Psychol 2009;38(3):315-28.
19. Ezpeleta L, de la Osa N, Domenech JM. Prevalence of DSM-IV disorders,  comorbidity  and  impairment  in  3-year-old  Spanish preschoolers. Soc Psychiatry Psychiatr Epidemiol 2014;49(1):14555.
20. Kadesjo C, Hagglof B, Kadesjo B, Gillberg C. Attention-deficithyperactivity disorder with and without oppositional defiant disorder  in  3-  to  7-year-old  children.  Dev  Med  Child  Neurol 2003;45(10):693-9.
21. Lahey  BB,  Loeber  R,  Burke  JD,  Applegate  B.  Predicting  future antisocial personality disorder in males from a clinical assessment in childhood. J Consult Clin Psychol 2005;73(3):389-99.
22. Lahey  BB,  Van  Hulle  CA,  Rathouz  PJ,  Rodgers  JL,  D'Onofrio BM,  Waldman  ID.  Are  oppositional-defiant  and  hyperactiveinattentive symptoms developmental precursors to conduct problems  in  late  childhood?:  genetic  and  environmental  links.  J Abnorm Child Psychol 2009;37(1):45-58.
23. Mannuzza S, Klein RG, Abikoff H, Moulton JL, III. Significance of childhood conduct problems to later development of conduct disorder  among  children  with  ADHD:  a  prospective  follow-up study. J Abnorm Child Psychol 2004;32(5):565-73.
24. Moffitt TE, Caspi A, Harrington H, Milne BJ. Males on the lifecourse-persistent and adolescence-limited antisocial pathways: follow-up at age 26 years. Dev Psychopathol 2002;14(1):179-207.
25. Burke JD, Rowe R, Boylan K. Functional outcomes of child and adolescent oppositional defiant disorder symptoms in young adult men. J Child Psychol Psychiatry 2014;5(3):264-72.
26. Bendiksen B, Svensson E, Aase H, et al. Co-Occurrence of ODD and  CD  in  Preschool  Children  With  Symptoms  of  ADHD.  J Atten Disord 2014 Jul 3.
27. Posner K, Melvin GA, Murray DW, Gugga SS, Fisher P, Skrobala A,  et  al.  Clinical  presentation  of  attention-deficit/hyperactivity disorder  in  preschool  children:  the  Preschoolers  with  AttentionDeficit/Hyperactivity Disorder Treatment Study (PATS). J Child Adolesc Psychopharmacol 2007;17(5):547-62.
28. Magnus  P, Irgens LM,  Haug  K,  Nystad W,  Skjaerven R, Stoltenberg C. Cohort profile: the Norwegian Mother and Child Cohort Study (MoBa). Int J Epidemiol 2006;35(5):1146-50.
29. Achenbach TM. Child Behavior Checklist, 2000.
30. Egger HL, Angold A. The Preschool Age Psychiatric Assessment (PAPA): a structured  parent  interview  for diagnosing  psychiatric disorders  in  preschool  children.  In:  Del  Carmen-Wiggins  R,  A. Carter  A  (Eds):  Handbook  of  infant,  toddler,  and  preschool mental  health  assessment.  New  York,  NY:  Oxford  University Press; 2004, pp. 223-43.
31. Egger HL, Erkanli A, Keeler G, Potts E, Walter BK, Angold A. Test-retest reliability of the Preschool Age Psychiatric Assessment (PAPA). J Am Acad Child Adolesc Psychiatry 2006;45(5):538-49.
32. Keenan K, Wakschlag LS, Danis B, et al. Further evidence of the reliability  and  validity  of  DSM-IV  ODD  and  CD  in  preschool children. J Am Acad Child Adolesc Psychiatry 2007;46(4):457-68.
33. Magnus  P,  Haug  K,  Nystad  W,  Skjaerven  R.  [The  mother  and child cohort study will give new answers]. Tidsskr Nor Laegeforen 2006;126(13):1747-9.
34. Roid GH.  Stanford-Binet Intelligence Scales (SB5). Rolling Meadows, IL: Riverside Publishing; 2003.
35. Cohen  J, Cohen  P,  West  SG,  Aiken  LS.  Applied multiple regression/correlation analysis for the behavorial sciences. 3 rd  ed. Mahwah, NJ: Lawrence Elbaum Associates; 2003.
36. Nigg  JT. Attention-deficit/hyperactivity disorder and  adverse health outcomes. Clin Psychol Rev 2013;33(2):215-28.
37. Simonoff E, Pickles A, Meyer JM, Silberg JL, Maes HH, Loeber R, et al. The  Virginia twin study of adolescent behavioral development. Influences of age, sex, and impairment on rates of disorder. Arch Gen Psychiatry 1997;54(9):801-8.
38. Wille  N,  Bettge  S,  Wittchen  HU,  Ravens-Sieberer  U.  How impaired are children and adolescents by mental health problems? Results  of  the  BELLA  study.  Eur  Child  Adolesc  Psychiatry 2008;17 Suppl 1:42-51.
39. Lahey BB, Pelham WE, Stein MA, Loney J, Trapani C, Nugent K, et  al.  Validity  of DSM-IV attention-deficit/hyperactivity disorder for  younger  children.  J  Am  Acad  Child  Adolesc  Psychiatry 1998;37(7):695-702.
40. Wichstrom L, Berg-Nielsen TS, Angold A, Egger HL, Solheim E, Sveen TH. Prevalence of psychiatric disorders in preschoolers. J Child Psychol Psychiatry 2012;53(6):695-705.
41. Gadow  KD,  Sprafkin  J,  Nolan  EE.  DSM-IV  symptoms  in community  and  clinic  preschool  children.  J  Am  Acad  Child Adolesc Psychiatry 2001;40(12):1383-92.
42. Biederman J, Kwon A, Aleardi M, Chouinard VA, Marino T, Cole H, et al. Absence of gender effects on attention deficit hyperactivity  disorder:  findings  in  nonreferred  subjects.  Am  J Psychiatry 2005;162(6):1083-9.
43. Gaub  M,  Carlson  CL.  Gender  differences  in  ADHD:  a  metaanalysis and critical review. J Am Acad Child Adolesc Psychiatry 1997;36(8):1036-45.
44. Novik  TS,  Hervas  A,  Ralston  SJ,  et  al.  Influence  of  gender  on attention-deficit/hyperactivity disorder in Europe--ADORE. Eur Child Adolesc Psychiatry 2006;15 Suppl 1:I15-I24.
45. Rapee RM, Bogels SM, van der Sluis CM, Craske MG, Ollendick T. Annual research review: Conceptualising functional impairment in children and adolescents. J Child Psychol Psychiatry 2012;53(5):454-68.
46. Krueger  RF,  Markon  KE.  Reinterpreting  comorbidity:  a  modelbased approach to understanding and classifying psychopathology. Annu Rev Clin Psychol 2006;2:111-33.
47. Nilsen  RM,  Vollset  SE,  Gjessing  HK,  Skjaerven  R,  Melve  KK, Schreuder  P,  et  al.  Self-selection  and  bias  in  a  large  prospective pregnancy cohort in Norway. Paediatr Perinat Epidemiol 2009;23(6):597-608.
48. Goodman R, Ford T, Simmons H, Gatward R, Meltzer H. Using the Strengths and Difficulties Questionnaire (SDQ) to screen for child psychiatric disorders in a community sample. Br J Psychiatry 2000;177:534-9.
49. O'Neill  S,  Schneiderman  RL,  Rajendran  K,  Marks  DJ,  Halperin JM. Reliable ratings or reading tea leaves: can parent, teacher, and clinician behavioral ratings of preschoolers predict ADHD at age six? J Abnorm Child Psychol 2014;42(4):623-34.

50. Reiersen  AM,  Todorov  AA.  Exploration  of  ADHD  subtype definitions and co-occurring psychopathology in a Missouri population-based  large  sibship  sample.  Scand  J  Child  Adolesc Psychiatr Psychol 2013;1(1):3-13.
51. Angold  A,  Costello  EJ,  Farmer  EMZ,  Burns  BJ,  Erkanli  A. Impaired but undiagnosed. J Am Acad Child Adolesc Psychiatry 1999;(2):129-37.
52. Chacko  A,  Wakschlag  L,  Hill  C,  Danis  B,  Espy  KA.  Viewing preschool disruptive behavior disorders and attentiondeficit/hyperactivity disorder through a developmental lens: what we know and what we need to know. Child Adolesc Psychiatr Clin N Am 2009;18(3):627-43.
53. Kim-Cohen J, Arseneault L, Newcombe R, Adams F, Bolton H, Cant  L,  et  al.  Five-year  predictive  validity  of  DSM-IV  conduct disorder  research  diagnosis  in  4(1/2)-5-year-old  children.  Eur Child Adolesc Psychiatry 2009;18(5):284-91.

## Acknowledgments

We are most grateful to the participating families in Norway who are taking part in this ongoing study. We  also  want  to  thank  the clinicians and  the research assistants for their work with children and families and the collection of data.

## Funding

The  present  study  was  supported  by  Grant  No. 39289  from  the  South  Eastern Health  Region; funding  from  the  Norwegian  Resource  Centre  for ADHD, Tourette's Syndrome, and Narcolepsy; and funding from Oslo University Hospital. Data were drawn  from  the  Norwegian  Longitudinal  ADHD Study,  which  was  supported  by  funds  and  grants from the Norwegian Health Directorate; the Norwegian  Ministry  of  Health;  the  South  Eastern Health Region, the G&P  Sorensen Fund for Scientific  Research;  and  the  Norwegian  Resource Centre for ADHD,  Tourette's Syndrome, and Narcolepsy.  The  Norwegian  Mother  and  Child Cohort  Study  was  supported  by  the  Norwegian Ministry  of  Health  and  the  Ministry  of  Education and Research; NIH/NIEHS (Contract No. NO-ES75558);  NIH/NINDS  (Grant  No.  1  UO1  NS 047537-01); and the Norwegian Research Council/FUGE (Grant No. 151918/S10).