Attention deficit hyperactivity disorder (ADHD) is a common neurodevelofirst aim was to determine the differences in comorbidities and functional impairments between children with pmental disorder in children and adolescents. Recent studies have shown that the worldwide prevalence in children and adolescents is 3.4%,1 and the prevalence in China is 5.7%.2 Therefore, prevention and treatment of ADHD have become urgent global public health goals.
The characteristic symptoms of ADHD are inattentiveness, hyperactivity and impulsiveness, which are more inappropriate than those in children of a comparable age. As a result, the disorder can be categorised as follows: ADHD, predominantly inattentive type (ADHD-I); ADHD, predominantly hyperactivity (ADHD-H); and ADHD, combined type (ADHD-C).3 Most children with ADHD have functional impairments in family, academic, social activities and self-concept. The more severe the symptoms of ADHD are, the greater the functional impairments. Furthermore, ADHD persists into adulthood in approximately 50% of patients,4 and patients with ADHD are at higher risk for other mental disorders.5
Comorbidities are thought to be one of the most important aspects of ADHD. The overall prevalence of psychiatric disorders associated with ADHD ranges from 40% to 80%, depending on the composition of the sample.6 The most common comorbidities include oppositional defiant disorder (ODD), anxiety disorders,7 conduct disorder (CD), learning disorders and tic disorders (TDs).8 Among the comorbidities, ODD has the highest prevalence (32%–50%),9 10 while the prevalence of CD, anxiety disorder and depression have been reported to be 24%–30%, 25%–33% and 20%, respectively.10 11 The comorbidity rates vary because of confounding factors, such as age, ADHD symptom severity and medication use.7 Although ADHD comorbidities have been widely studied,10 12 some issues remain unsolved. In clinical practice, comorbidities may mask the core symptoms of ADHD; in contrast, ADHD may be masked by comorbidities, thus making the diagnostic process challenging. While most studies have only focused on the current prevalence of ADHD comorbidities, few studies have addressed the effects of comorbidities on social functions in children with ADHD.13 14 Most of the existing studies involving children with ADHD in China have been conducted on small-scale community samples. The core symptoms and comorbidities were relevant and also affected functional impairments. Given the limited research conducted on this topic and its importance for prevention and intervention strategies, this hospital-based cross-sectional study addressed the associations between comorbidities, core symptoms of ADHD and functional impairments in children with ADHD. The first aim was to determine the differences in comorbidities and functional impairments between children with and without ADHD. The second aim was to analyse the effects of comorbidities on the functional impairments in children with ADHD. The third aim was to analyse the effects of different subtypes of ADHD on the functional impairments in children with ADHD. Finally, we analysed the risk factors related to each functional impairment in children with ADHD based on logistic regression analysis.
A total of 10 698 children, 6–17 years of age, were enrolled in a hospital-based retrospective cross-sectional study in China between August 2016 and April 2019.
The study participants were evaluated for behavioural problems, such as inattentiveness and hyperactivity, for the first time in the Department of Child and Adolescent Healthcare, Children’s Hospital of Soochow University, in Suzhou, China. Each participant was assessed IQ using the Weschler Intelligence Scale for Children. Patients were excluded if they met any of the following criteria: (1) organic lesions of the nervous system, intellectual disability (IQ <70 points), a psychotic disorder or an extensive developmental disorder; and (2) history of treatment with central nervous system stimulants, including drugs for ADHD, or long-term pharmaceutical treatment for other chronic diseases.
Based on the exclusion criteria, 485 children and adolescents were excluded; 1957 declined to participate in the study or withdrew consent. Thus, the study cohort consisted of 8256 children and adolescents (77.2%). Written informed consent was obtained from the parents or guardians of the participants.
Neither the patients nor the public were directly involved in the design, recruitment or assessment of this study.
The patients were diagnosed and classified by developmental paediatricians after obtaining a relevant history and clinical assessment using an ADHD rating scale with diagnostic criteria consistent with the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5 ).3 Those children and adolescents who met the diagnostic criteria were classified as the ADHD group; the children and adolescents who did not meet the diagnostic criteria were classified as the N-ADHD group. Among the 18 symptoms, patients were diagnosed with ADHD-I when at least six of the inattentive symptoms were met, ADHD-H when at least six of the hyperactivity symptoms were met and ADHD-C when the patients qualified as ADHD-I and ADHD-H. The Vanderbilt ADHD Diagnostic Parent Rating Scale (VADPRS)15 was filled out by parents under the guidance of specialists and was used for comorbidity screening. Twenty-nine comorbidity symptoms were screened, among which 8 items were used to assess ODD, 14 items were used to assess CD and 7 items were used to assess anxiety and depression disorder (Anx-Dep). Each item was rated as never (0), occasionally (1), often (2) or always (3). ODD was diagnosed when at least four items of the ODD symptoms scored 2 or 3, CD was diagnosed when at least three items of the CD symptoms scored 2 or 3 and Anx-Dep was diagnosed when at least three items of the Anx-Dep symptoms scored 2 or 3. Patients with at least one positive diagnosis (ODD, CD or Anx-Dep) were considered to have a comorbidity. Xiao et al 16 examined a Chinese adaption of the VADPRS in a clinical sample of children with ADHD and verified that the specificity was 0.63 and the sensitivity was 0.83.
The Weiss Functional Impairment Rating Scale-Parent Form (WFIRS-P) was completed by the parents of the patients under the guidance of specialists and was used to assess the functional impairments of children with ADHD. The scale consists of six dimensions, including family, academic, life skills, self-concept, social activities and risky activities. Each dimension includes a number of items, and each item is rated from 0 to 3 (0=never, 1=sometimes, 2=often and 3=always or frequently). Functional impairment of each domain was present based on a score of 3 in any item, a score of 2 in both items or an average score >1.5. Higher scores indicate more severe functional impairment. All of the dimensions demonstrated good reliability, and the Cronbach’s alpha coefficient was >0.7 for all domains.17
SPSS V.22 (IBM Corp, Armonk, New York, USA) was used for statistical analysis. Measurement data, such as age, IQ and VADPRS and WFIRS-P scores, are expressed as the mean (95% CI). Comparisons between two groups were made using t-tests. Comparisons between ADHD-I, ADHD -H and ADHD-C were made with the analysis of variance. Classification data, such as gender, proportion of comorbidities and proportion of functional impairments, are expressed as the percentage (95% CI), and χ2 tests were used for comparisons between two groups. Binary logistic regression analysis was used to determine the associations between functional impairments and core ADHD symptoms, comorbidities, age, gender and IQ. The effects of independent variables on dependent variables are represented by ORs. Statistical significance was set at a p<0.05.
According to the ADHD clinical diagnostic criteria in DSM-5 , 5640 children were diagnosed with ADHD. The remaining 2616 children were included in the N-ADHD group. There were 4717 males (83.6%) in the ADHD group, which was a significantly higher percentage than the N-ADHD group (p<0.05). Although the average age did not differ significantly between the two groups, the average IQ was lower in the ADHD group than the N-ADHD group (p≤0.001) (table 1).
|Characteristic||ADHD (n=5640)||N-ADHD (n=2616)||t/χ2||P value|
|Male||83.6 (82.7 to 84.6)||81.3 (79.7 to 82.8)||6.61||0.011|
|Female||16.4 (15.5 to 17.4)||18.7 (17.2 to 20.1)|
|Age||8.27 (8.22 to 8.30)||8.23 (8.16 to 8.30)||0.84||0.403|
|IQ||113.85 (113.40 to 114.30)||115.61 (114.96 to 116.27)||−4.37||0.000|
|Proportion with total comorbidities||47.4 (46.1 to 48.7)||24.1 (22.6 to 25.9)||400.30||0.000|
|Proportion with ODD comorbidity||42.6 (41.3 to 43.9)||21.5 (19.9 to 23.1)||344.619||0.000|
|Proportion with CD comorbidity||6.3 (5.7 to 7.0)||1.3 (0.8 to 1.7)||101.999||0.000|
|proportion with Anx-Dep comorbidity||12.4 (11.6 to 13.3)||5.2 (4.3 to 6.0)||103.745||0.000|
|Proportion with one comorbidity||35.3 (34.0 to 36.5)||20.8 (19.2 to 22.3)||176.931||0.000|
|Proportion with two comorbidites||10.4 (9.6 to 11.2)||3.2 (2.6 to 3.9)||122.482||0.000|
|Proportion with three comorbidites||1.8 (1.4 to 2.1)||0.2 (0 to 0.4)||33.142||0.000|
|Proportion of functional impairments||84.5 (83.6 to 85.5)||66.9 (65.1 to 68.7)||333.90||0.000|
|Family||0.62 (0.61 to 0.63)||0.36 (0.35 to 0.38)||26.06||0.000|
|Academic||0.79 (0.78 to 0.80)||0.49 (0.48 to 0.50)||30.92||0.000|
|Life skills||0.93 (0.92 to 0.94)||0.68 (0.67 to 0.69)||28.55||0.000|
|Self-concept||0.77 (0.76 to 0.79)||0.52 (0.50 to 0.54)||17.62||0.000|
|Social activities||0.75 (0.74 to 0.77)||0.54 (0.52 to 0.55)||19.84||0.000|
|Risky activities||0.28 (0.28 to 0.29)||0.18 (0.17 to 0.18)||20.56||0.000|
Comorbidities (including ODD, CD and Anx-Dep) were identified in 2675 children (47.4%) in the ADHD group, which was a significantly higher percentage than the N-ADHD group (p≤0.001). The proportion with ODD (42.6%), CD (6.3%) and Anx-Dep (12.4%) in the ADHD group were higher than the N-ADHD group (p≤0.001). Additionally, the proportion with one comorbidity (35.3%), two comorbidities (10.4%) and three comorbidities(1.8%) in the ADHD group were higher than the N-ADHD group (p≤0.001)
The proportion of functional impairments in the ADHD group was higher than the N-ADHD group (p≤0.001). Similarly, the functional impairment scores in all domains were significantly higher in the ADHD group than the N-ADHD group (p≤0.001; table 1).
Functional impairment in children and adolescents with comorbidities was more severe than those without comorbidities; the differences were statistically significant (table 2). Designating the impairment scores of each functional domain for children and adolescents with ADHD as dependent variables and the number of comorbidities as an independent variable, univariate linear regression analysis showed that as the number of comorbidities increased, so did the degree of functional impairment for each dimension in children with ADHD (table 3).
|WFIRS-P score||ADHD children with comorbidites (n=2675)||ADHD children without comorbidites (n=2965)||t||P value|
|Family||0.79 (0.77 to 0.81)||0.46 (0.45 to 0.47)||30.14||0.000|
|Academic||0.87 (0.85 to 0.89)||0.73 (0.71 to 0.74)||12.23||0.000|
|Life skills||1.03 (1.01 to 1.04)||0.84 (0.83 to 0.85)||18.55||0.000|
|Self-concept||0.96 (0.93 to 0.98)||0.61 (0.59 to 0.63)||21.27||0.000|
|Social activities||0.90 (0.88 to 0.92)||0.62 (0.61 to 0.64)||22.30||0.000|
|Risky activities||0.34 (0.33 to 0.35)||0.23 (0.22 to 0.23)||19.25||0.000|
|WFIRS-P score||Β (95% CI)||SE||t||P value|
|Family||0.268 (0.254 to 0.282)||0.007||37.62||0.000|
|Academic||0.131 (0.116 to 0.146)||0.008||16.78||0.000|
|Life skills||0.145 (0.132 to 0.158)||0.007||21.55||0.000|
|Self-concept||0.291 (0.269 to 0.312)||0.011||26.69||0.000|
|Social activities||0.239 (0.223 to 0.255)||0.008||29.50||0.000|
|Risky activities||0.101 (0.093 to 0.109)||0.004||25.01||0.000|
The degree of functional impairment was dependent on the subtype of ADHD. Specifically, the degree of functional impairment was higher in the ADHD-C group than in either of the other two groups. The most apparent impairment among the six WFIRS-P functional domains in all three types of ADHD (I, H and C) was life skills (table 4).
|WFIRS-P score||ADHD-I (n=2784)||ADHD-H (n=530)||ADHD-C (n=2326)||F||P value|
|Family||0.53 (0.51 to 0.55)||0.56 (0.53 to 0.60)||0.74 (0.72 to 0.76)*||149.76||0.000|
|Academic||0.73 (0.72 to 0.75)*||0.62 (0.59 to 0.65)*||0.90 (0.88 to 0.92)*||142.45||0.000|
|Life skills||0.87 (0.86 to 0.89)*||0.83 (0.80 to 0.85)*||1.02 (1.00 to 1.04)*||116.91||0.000|
|Self-concept||0.79 (0.76 to 0.81)||0.57 (0.52 to 0.62)*||0.80 (0.76 to 0.83)||30.29||0.000|
|Social activities||0.68 (0.66 to 0.70)||0.69 (0.66 to 0.73)||0.85 (0.83 to 0.87)*||89.01||0.000|
|Risky activities||0.24 (0.23 to 0.25)*||0.26 (0.24 to 0.28)*||0.34 (0.33 to 0.35)*||122.83||0.000|
The functional impairments included six domains, as follows: family; academic; life skills; self-concept; social activities; and risky activities. Designating the existence of impairment (evaluated based on a score of 3 in any item, a score of 2 in both items or an average score >1.5) in each functional domain as the dependent variable, and the inattentiveness, hyperactivity, ODD, CD and Anx-Dep scores12; the number of comorbid disorders, and the ADHD subtype (ADHD-I: 1, ADHD-H: 2 and ADHD-C: 3) as independent variables, and after correcting for confounding factors (age, gender and IQ), binary logistic regression analysis showed that the ODD, CD, Anx-Dep, inattentiveness and hyperactivity scores were associated with functional impairments in different domains. The severity of comorbidities had greater impact on all of the six functional domains compared with the severity of core symptoms. For the domains of family (OR=1.30), academic (OR=1.21) and risk activities (OR=1.36), CD symptom score had the most significant influence. However, life skills (OR=1.21) and self-concept (OR=1.78) were most significantly influenced by Anx-Dep symptom score, and social activities (OR=1.35) was most influenced by the number of comorbidities (table 5).
|Family||Academic||Life skills||Self-concept||Social activities||Risky activities|
|Inattentiveness score, OR (95% CI)||1.04 (0.99 to 1.09)||1.10* (1.06 to 1.14)||1.06* (1.02 to 1.10)||1.19* (1.12 to 1.26)||0.99 (0.94 to 1.03)||1.11* (1.04 to 1.19)|
|Hyperactivity score, OR (95% CI)||1.08* (1.05 to 1.11)||1.06* (1.03 to 1.08)||1.08* (1.06 to 1.11)||1.01 (0.95 to 1.07)||1.08* (1.05 to 1.10)||1.11* (1.07 to 1.15)|
|ODD score, OR (95% CI)||1.21* (1.17 to 1.25)||1.01 (0.99 to 1.04)||1.06* (1.04 to 1.09)||1.08* (1.04 to 1.12)||1.03 (0.98 to 1.07)||1.05* (1.01 to 1.10)|
|CD score, OR (95% CI)||1.30* (1.21 to 1.39)||1.21* (1.15 to 1.28)||1.04 (0.98 to 1.10)||1.05 (0.96 to 1.15)||1.26* (1.18 to 1.36)||1.36* (1.26 to 1.47)|
|Anx-Dep score OR (95% CI)||1.28* (1.23 to 1.34)||1.15* (1.11 to 1.20)||1.21* (1.16 to 1.26)||1.78* (1.69 to 1.87)||1.18* (1.12 to 1.24)||1.25* (1.19 to 1.32)|
|No. of comorbid disorders OR (95% CI)||0.95 (0.79 to 1.15)||0.98 (0.83 to 1.15)||0.99 (0.85 to 1.17)||0.93 (0.76 to 1.13)||1.35*(1.19 to 1.53)||0.93 (0.73 to 1.18)|
|ADHD subtypes OR (95% CI)||1.05 (0.92 to 1.19)||1.02 (0.92 to 1.13)||0.97 (0.87 to 1.07)||0.94 (0.85 to 1.02)||1.04 (0.92 to 1.17)||0.99 (0.83 to 1.18)|
The first objective of this study was to determine the differences in comorbidities and adaptive functioning in different domains of daily life between children and adolescents with and without ADHD. We found that the overall rate of functional impairment in children and adolescents with ADHD was significantly higher than in children and adolescents with N-ADHD. Functional impairment scores for each of the six domains (family, academic, life skills, self-concept, social activities and risky activities) were significantly higher for children and adolescents with ADHD. These findings are consistent with previous studies showing that children and adolescents with ADHD had more problems across a wide range of academic, social and family function indicators.18 19 Although the core symptoms of inattentiveness and hyperactivity are partially alleviated during development, ADHD symptoms for 70%–85% of children persist into adolescence and can persist into adulthood for approximately 50% of children.4 When symptoms persist, people can easily develop antisocial personality disorder, CD, drug and/or alcohol abuse and/or juvenile delinquency.20 21 The high prevalence of functional impairment (84.5%) in children and adolescents with ADHD indicated that existing management strategies do not meet the needs.
The second objective of this study was to analyse the effects of comorbidities on functional impairment in children and adolescents ADHD. Most children with ADHD have at least one comorbidity. The main comorbidities are ODD (20%–60%), CD (20%–50%), and Anx-Dep disorders (10%–40%).6 12 22–25 We found that ODD affected 42.6% of all children and adolescents with ADHD, which is similar to the previously reported findings6; however, in our sample, the proportion of children and adolescents with ADHD accompanied by CD and Anx-Dep were only 6.3% and 12.4%, respectively, which were lower than previously reported.10 24 26
The discrepant findings can be due to the following: rates of comorbidities reported in the literature vary widely due to different definitions of comorbid conditions, ages of the study cohorts and origin of samples; the participants in our study were evaluated from the Department of Child Health Care of the hospital setting for behavioural problems for the first time, so the severity of comorbidities of our participants may be less than those from paediatric psychiatric clinics; the scales were completed by their parents and symptoms, such as some internalising problems, may not have been exhibited or recognised by the parents, and the comorbidity assessments in our study were performed using a screening survey due to the large sample size. Nevertheless, our current findings support an emerging view that ADHD existed in the absence of comorbidities in only a minority of cases. In agreement with the literature, we found that among children and adolescents with ADHD, those with comorbidities had more problems compared with those without comorbidities across a wide range of daily life function indicators. The functional impairments in children and adolescents with ADHD and comorbidities were shown to differ depending on the comorbidity. Virring et al 13 reported that internalising or autistic comorbid disorders are significantly associated with the degree of sleep problems in children with ADHD. The effect of ADHD and comorbidities on daily life functions was associated with the type of comorbidity and the number of comorbidities. Larson et al 8 showed that the majority (67%) of children with ADHD had at least one comorbidity, 16% had two comorbidities and 18% had ≥3 comorbidities. In this study, the overall detection rate of comorbidities in children and adolescents with ADHD (47.4%) was lower than reported in previous studies8; specifically, 10.4% of children and adolescents with ADHD had two comorbidities and 1.8% had three comorbidities. Despite the lower number, linear regression analysis indicated that the degree of impairment on several functional domains increased linearly with the number of comorbidities, which was consistent with the conclusion of the study conducted in the USA in 2007. Other studies have indicated that more comorbidities are predictive to ADHD continuing from childhood to adulthood,4 and the number of comorbid disorders, particularly anxiety disorders, was significantly related to long-term work disability.21
The third objective of the current study was to analyse the relationship between functional impairment in different types of ADHD. Although previous studies have shown that functional impairment in ADHD is related to core symptoms,17 18 the conclusions regarding the influence of different subtypes of ADHD were not consistent. For example, a study conducted in China found that the severity of core symptoms in ADHD influenced the occurrence of comorbidities and functional impairments, with the ADHD-C group having a significantly higher overall incidence of functional impairments than the ADHD-I or ADHD-H group.27 Another study involving university students with ADHD showed that parent-reported anxiety symptoms were higher for students with ADHD-I than for those with the combined ADHD subtype.28 Castagna et al 29 reported that youth diagnosed with ADHD-C had more frequent personal failures and hostile intent negative self-statements than those diagnosed with ADHD-I. In the current study, we found that the degree of impairment for all six functional domains in the ADHD-C group was higher than the ADHD-I or ADHD-H group.
Although previous studies have shown that in general, comorbidity and core symptoms can affect the daily life functions of children with ADHD, as far as different social functions are concerned, the specific factors that play decisive roles in their impairment remain unclear. Therefore, the final objective of the current study was to analyse the risk factors associated with each functional domain in ADHD using logistic regression analysis. The results showed that the different comorbidities were related to specific functional domains. For the domains of family (OR=1.30), academic (OR=1.21) and risk activities (OR=1.36), CD symptom score had the most significant influence. In contrast, life skills (OR=1.21) and self-concept (OR=1.78) were most significantly influenced by Anx-Dep symptom score, and social activities (OR=1.35) was most influenced by the number of comorbidities. Therefore, we conclude that in most functional domains, the effect of comorbidities on functional impairment exceeded the effects of ADHD core symptoms.
The current study also showed that the incidence of CD, ODD or Anx-Dep in the N-ADHD group (2616 children) was 24.1%, and the main complaint of these children was multidomain functional impairments. Over the years, clinical efforts have been made to alleviate the core symptoms of children with ADHD, but there are still many patients in whom symptoms can persist into adolescence and adulthood. This is especially true when comorbidities and functional impairments have not been alleviated because functional impairments have an extensive and negative impact on learning, social interactions and daily life.19 21 Thus, although inattentiveness or hyperactivity symptoms in some children are not apparent and do not meet the diagnostic criteria for ADHD, clinicians should make efforts to screen and treat these other conditions because the persistence of CD, ODD and/or Anx-Dep may be the main reason social functioning does not improve.
In addition to different clinical significances and prognoses, responses to treatment also depend on the type of comorbidity, indicating that the existence of a comorbidity can affect the ADHD treatment strategy.11 The Multimodal Treatment Study of Children with ADHD (MTA) reported the behaviour and the drug response of children with different types of ADHD comorbidities, finding that children with ADHD only or ADHD with ODD/CD, but without anxiety disorders, responded best to MTA medication treatments, with or without behavioural treatments.24 Moreover, children with multiple comorbid disorders (anxiety and ODD/CD) responded optimally to combined (medication and behavioural) treatments.24 The second edition of the Chinese ADHD Prevention and Treatment Guidelines30 also pointed out that children with ADHD are often accompanied by a variety of psychological and developmental diseases. Thus, the diagnosis and treatment of ADHD comorbidities is essential. Specifically, given that stimulants may increase the risk of twitching, the second edition of the Chinese ADHD Prevention and Treatment Guidelines recommends atomoxetine and clonidine as preferred drugs for the treatment of ADHD when accompanied by a TD. In addition, nearly one-third of children with ADHD have anxiety, and stimulants may also increase anxiety symptoms. Therefore, the second edition of the Chinese ADHD Prevention and Treatment Guidelines recommends atomoxetine as first-line treatment of ADHD when accompanied by anxiety.
This study had some limitations. First, participants were screened from the clinic of one children’s hospital, and the cross-sectional design did not enable conclusions about causality. The N-ADHD group was not pure. There were >80 000 person-time per year visiting the Department of Child Health Care in our hospital. This was a limitation in our study, but we believe that it also gave us insight that children suspected of ADHD should receive close attention with respect to functional impairments. Fortunately, several results were consistent with those previously reported in multicentre studies conducted in other countries. Second, assessment from parents should be treated with caution due to possible recall bias. Because of the nature of the available data, the factors included in the logistic regression analysis and the family and social environmental factors were limited; however, the large sample size allowed meaningful results to be obtained.
ADHD should not be regarded as a single disease but as a comprehensive state comprising a group of diseases. The influence of comorbidities on social function in ADHD can exceed that of the core symptoms. Early clinical classification, comorbidity analysis and functional impairment assessment in children suspected of having ADHD are crucial for determining treatment and prognosis. Furthermore, the existence of a comorbidity can lead to changes in the ADHD treatment strategy. Additional studies about ADHD comorbidity problems are needed to further individualise interventions.
We would like to thank International Science Editing (http://www.internationalscienceediting.com) for editing this manuscript. We would also like to thank Dr. Chen Kui and Professor Li Hongmei from the School of Public Health, Soochow University for the guidance of data analysis.