ASW Tong, MMF Wu, SKY Liu

Abstract

Introduction: Dual diagnosis of Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) was first recognised officially in 2013. This study aimed to examine the prevalence of their comorbidity in children in the largest public child assessment service in Hong Kong. Methods: The medical data of children with birth year 2012 and 2013 who underwent assessment in Child Assessment Service up to 31st December 2021 with diagnosis ASD and/or ADHD/related diagnosis were retrieved. Data was divided into three groups, children with either ADHD or ASD, and those with both conditions. Their developmental profiles were analysed. Results: 8639 cases with ASD, ADHD/related diagnosis and dual diagnosis were reviewed. Sixteen percent of ADHD/related diagnosis children were also diagnosed with ASD, while 24% of ASD children had comorbid ADHD/related conditions. Conclusion: More awareness on the common comorbidity of ASD and ADHD in children is crucial, early identification of such can allow more efficient management.

Introduction

Comorbid Autism Spectrum Disorder (ASD) in children with Attention Deficit Hyperactivity Disorder (ADHD) and vice versa was not recognised previously by the Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition, Text Revision (DSM-IV-TR).¹ It was not until in Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition (DSM-5)² that the dual diagnosis of both disorders is allowed based on emerging scientific understanding on the two common neurodevelopmental conditions.

Numerous literatures focusing on the similarity of the two conditions in terms of symptomatology and the presence of shared genetic factors were published.^3-6 Frequent co-occurrence of ASD and ADHD in the same individual has also been reported widely especially after the formal establishment of DSM-5.

Individuals with ASD were proved to be at higher risk of having ADHD compared to those without ASD (OR=22.33, 95% CI:21.77-22.92) in a large Swedish cohort, this association also occurred within a family but with different degrees depending on the relationship with the proband.⁷ Almost half of the individuals with ASD (48%) had coexisting ADHD while around 17% of ADHD individuals also had ASD in European data.⁷ Fourteen percent of ADHD children were reported to be suffering from ASD according to the Centers for Disease Control and Prevention.⁸ In our population, a study involving children aged 6-11 showed nearly one in every two ASD children in a child psychiatric clinic also had comorbid ADHD.⁹ The range of figures regarding the comorbidities between ASD and ADHD varies in different studies and limited local data on the prevalence of ASD in ADHD were available.

The Child Assessment Service (CAS) of Department of Health is the major public organisation that serves children who are under 12 years of age with developmental-behavioural problems or disorders in the Hong Kong. There are seven centers in different regions of Hong Kong which cover the whole territory. It provides comprehensive assessment to children with special developmental-behavioural needs by various professional disciplines.

Our study aimed to examine the prevalence of comorbidity between ASD and ADHD in the largest public child assessment service in Hong Kong and their corresponding clinical profiles.

Methods

Source and Features of Cohort Data
Data was retrieved using the CAS Information System, an electronic system containing data from all Child Assessment Centres under CAS of Department of Health. All electronic medical data of children with birth year 2012 and 2013 who underwent assessment in our services with diagnosis ASD and/or ADHD/related diagnosis (ADHD, Attention Deficit Disorder (ADD), hyperactive problem, inattentive problem) were reviewed retrospectively. Cases with ASD and/or ADHD/related diagnosis (ADHD, Attention Deficit Disorder (ADD) and other associated comorbidities were codified by using ICD-10.¹⁰ All children were assessed and diagnosed by either Paediatricians or Clinical Psychologists. Children with hyperactive and inattentive problem were also included in the ADHD-related diagnosis group. It is because majority of the children being referred to CAS were at 2-4 years of age, most of them were diagnosed as having hyperactive or inattentive problems instead of ADHD, which may only be able to be confirmed later. Hence, their data was also included in our analysis. The ICD-10 codes were entered into the system after the assessments were completed. Protocols for clinical practice were adopted in the service and periodic quality assurance exercises were conducted to ensure the accuracy of coding. Selection bias and information bias were thus minimised.

This is a retrospective cohort study covering children with birth dates from 1st January 2012 to 31st December 2013. Their clinical data were retrieved from the CAS Information System up to 31st December 2021. The rationales for selecting these 2 years were as follows: first, the dual diagnosis of ASD and ADHD has only been formally permitted by DSM-5 in 2013.² Secondly, by the time our birth cohort was recruited, these children were 8 to 9 years old, in which the ASD and/or ADHD features should have been presented and diagnosed by the time of data collection.

Data was divided into three groups, children with 1) ADHD/related diagnosis-only, 2) ASD-only, and 3) Dual diagnosis of ASD and ADHD/related diagnosis. The clinical characteristics and developmental profiles of these children were analysed and comparison was made among the three groups. Baseline demographic data such as sex, age, reason of referral, diagnosis and comorbidities with age of each neurodevelopmental diagnosis were retrieved. Management and referral plan after assessment, for instance, referral to Child Psychiatric Clinic in Hospital Authority and the Preschool Rehabilitation Services, were reviewed. For school-aged children, the need for referral to Special Educational Services (SES) in mainstream school or referral to special school for different grade of intellectual disability were documented. Family History of Intellectual Disability, mental and behavioural disorders and substance abuse were also studied.

Data Analysis
Frequency distribution of different nominal or ordinal variables and the breakdown of those variables by ADHD group, ASD group and dual diagnosis group were analysed to examine the profile of each group. Chi-square or, when appropriate, Fisher's exact test was used to analyse the feature of cohort and their associations with occurrence of comorbidities, social background and significant family history. The statistical analyses were performed by using SPSS 26.0.¹¹ Statistical significance was set at p value <0.05 (two-tailed).

Results

A total of 8639 children with birth year 2012-2013 with diagnosis of ASD and/or ADHD-related diagnosis in the CAS were reviewed and analysed. Among these cases, 4874 children were diagnosed with ADHD/related problems, 2853 children with ASD diagnosis and 912 children had dual diagnosis of ASD and ADHD/related problems. Further analysis revealed that, 16% of children with ADHD-related diagnosis had ASD as well, while 24% of children with ASD had comorbid ADHD-related conditions.

Within the dual diagnosis group (n=912), nearly two-thirds (n=557) of them obtained both diagnoses in the same assessment, while one-third of them (n=313) had ASD being diagnosed first followed by ADHD. Only a minority (n=42) of them were diagnosed with ADHD first in our setting.

The male-to-female ratio was 2.1:1 for children with ADHD/related problems and 5.9:1 for children with ASD. For children with dual diagnosis, the male to female ratio increased to 7.4:1. At the time of assessment, the mean age was 5.4 years old in ADHD/related problem group, 3.2 years old in ASD group and 4.3 years old (when the first diagnosis was made) in dual diagnosis group.

Regarding the referral reasons in this cohort, they were identical in all three groups. The commonest referral reason was emotional/behavioral difficulties, followed by developmental delay and language problem.

Common Neurodevelopmental Comorbidities
In this cohort, the ASD group has the highest percentage of children diagnosed with intellectual disability or significant developmental delay (61.4%) (χ² (2) = 1269.94, P=0.000) among the three groups (Table 1).

Social Background and Significant Family History
It was important to note that the percentage of cases with family history of substance abuse in the ADHD group (1%) was 10 times more than that in the ASD group (0.1%) and 3.3 times more compared to the dual-diagnosis group (0.3%) (χ² (2) = 22.53, P=0.000). Majority of these cases had history of maternal substance abuse (Table 2). The most common drug being abused was (meth)amphetamine followed by ketamine. Specifically, among the 49 children in the ADHD group and with family history of substance abuse, 16 of them had family history of ADHD. Most of them were having affected siblings/half-siblings, and only 2 of them had affected parents.

Management and Referrals after Assessment in CAS
Nearly two-thirds (65.8%) of children in ADHD/related diagnosis group and majority (91.3%) of children in ASD group were referred to the Child Psychiatric Clinic in Hospital Authority for long-term follow-up and management. For children with dual-diagnosis, they have more behavioural and emotional challenges, and hence even higher percentage (93.5%) were referred to the child psychiatrists for further management and review.

In order to arrange early training and interventions for preschoolers, eligible children were referred to the preschool rehabilitation service under the Social Welfare Department in Hong Kong. These services include Early Education and Training Centre (EETC), Integrated Programme in Kindergarten-cum-Child Care Centre (ICCC), On-site Preschool rehabilitation Services (OPRS) or Special Child Care Centre (SCCC). The type of service referred depends on their degree of developmental delay and behavioral difficulties, some children might switch between services depends on their progress throughout preschool years. It should be noted that more children from ASD group were referred to SCCC and special schools. Nearly all children being referred to the special school for children with moderate and severe grade ID were in the ASD group (Tables 3 & 4).

Discussion

In this cohort, 16% children with ADHD-related diagnosis also had ASD. According to the CAS Epidemiology and Research Bulletin (CASER) on ADHD with data collected from 2011 to 2020, 15.8% of children with ADHD/ADD had comorbid ASD.¹² This figure is consistent with findings in our current study and previous overseas figures.^7,8

On the other hand, 24% of children with ASD had comorbid ADHD-related conditions in this cohort. In the CASER on ASD in 2020, it revealed that 16.3% of children with ASD had comorbid ADHD/related problems in 2018 in our service.¹³ Although the range of comorbidity varies greatly in different studies, the findings in our centers seem to be at a lower end of the range compared to studies in other settings.^7,9 This may be explained by the following reasons, firstly, majority of the referrals in our service are age 2 to 4 years old, which is usually too young to confirm the diagnosis of ADHD at this stage. Secondly, even if these cases developed comorbid ADHD in later stage of life after they were referred to the child psychiatric clinics, this information was not revealed in our study as different electronic medical data computer system was used in Hospital Authority.

Both ASD and ADHD are well-known to be male-predominant conditions. We specifically study the male-to-female ratio in children with dual diagnosis in this cohort, the ratio further increased to 7.4:1. This increase in the male prevalence ratio in children with ASD and ADHD was documented in previous publication in the western population.¹⁴

One important finding in our study is that Intellectual disability was much more common in ASD group (27.4%) when compared to ADHD group (3.8%) and dual diagnosis group (16.1%) (Table 1). In a large Sweden register-based cohort study, it has shown that ASD individuals were at higher risk of having ADHD (OR-22.33, 95% CI:21.77-22.92), while the magnitude of the association was larger in ASD without intellectual disability (ID) (OR=26.08, 95% CI:25:35-26.83) than those ASD individuals with ID (OR=1.25, 95% CI:1.61-1.34). A similar pattern of results was demonstrated in full siblings and full cousins.⁷ The reason behind this phenomenon is not yet well-understood, whether it is the real situation or is an underestimation of the real overlap in patients with triple diagnosis of ASD, ADHD and ID remains unknown. One of the possible postulations is that ASD children with ID are less likely to receive a third diagnosis of ADHD. Even if they present with some ADHD features, we may consider some of their behavior to be partly explained by the limited cognitive functions. Hence we may set a higher threshold before we make a third diagnosis of ADHD in ASD children with ID.

Only children with significant reading difficulties not better explained by other factors like intellectual disability can be diagnosed as dyslexia. The occurrence of comorbidity of dyslexia in ADHD group (10.3%) was similar to the general population, while the proportion is lower in ASD group and dual diagnosis group, which may partly be explained by the more frequent occurrence of intellectual disability in these group which make the diagnosis of dyslexia impossible (Table 1).

Another interesting finding in our study is that the percentage of cases with family history of substance abuse in ADHD group was 10 times more than that in the ASD group. Majority of the cases involved the history of maternal substance abuse. Specifically, among the 49 children in the ADHD-only group with family history of substance abuse, only 2 of them had affected parents. However, such figures may be partly affected by the limited public awareness and accessibility of formal assessment in the previous generations. Regarding the higher percentage of family history of substance abuse among the ADHD group, this has in fact been discussed in a previous pilot-controlled family study. The authors revealed that the rate of ADHD increased among children of parents with neither condition (3%), children of parents with substance abuse (13%), children of parents with ADHD (25%) and children of parents with both ADHD and substance abuse (50%).¹⁵

We have also tried to review the type of illicit drug used in families with history of substance abuse, however, not all cases contained detailed medical records in this aspect. The most common drug being abused and documented was (meth)amphetamine. This finding is consistent with another local study regarding mothers and children from the Comprehensive Child Development Service (CCDS), with amphetamine followed by ketamine as the commonest maternal illicit drug use.¹⁶ Maternal methamphetamine usage during pregnancy has been shown to be associated with increased emotional reactivity and anxious/depressed problems in their offspring at 3 and 5 years old, and associated with externalising and ADHD problems by 5 years old.¹⁷ However, the finding remains uncertain as to whether the risk for ADHD in the offspring of substance abuse parents is related to the substance abuse especially during pregnancy per se or if the parents may also have ADHD themselves. After all, increased awareness of clinicians to screen for ADHD features in developmental-behavioural assessment especially in children with family history of ADHD and/or substance abuse would be beneficial.

Multidisciplinary support is necessary to cater the special need of children with ASD or ADHD, while need of those with dual diagnosis are even more complex. Unsurprisingly, previous local study has shown the increased in total difficulty score in Strengths and Difficulties Questionnaire in dual diagnosis group when compared to children with ASD only. Children with dual diagnosis are also proven to be associated with significant increase in impact on different aspects, namely home, classroom and leisure activity impact and child distress.⁹ When encountering children with ASD and/or ADHD, clinicians should be more aware of the common comorbidity of both conditions, and early identification of such can allow a more efficient management. Having timely diagnosis especially in those with dual conditions can facilitate the parents, caretakers, and teachers to have a more accurate and all-rounded understanding on the clinical characteristics, strengths and weaknesses of their children. This also provides important information to the therapists and teachers when they try to set holistic training strategies and education plans to meet the children's specific and complex needs. Regarding pharmacological intervention, use of medication such as methylphenidate can reduce ADHD symptoms in children with ADHD with or without ASD. However, the efficacy of methylphenidate for treatment of ADHD in dual diagnosis group (Effect Size=0.67) is less than those with ADHD-only (Effect Size=1.03).^18,19 More adverse effects such as irritability and social withdrawal are expected in children with dual diagnosis, thus methylphenidate treatment should be carefully monitored in this group of patients.¹⁸

Strengths and Limitations

This study covers data from the largest public child assessment service in Hong Kong which consist of seven Child Assessment Centres. The multicenter service enables us to cover children across different regions in Hong Kong which makes it a more representative dataset. Moreover, all the children included in this paper have been individually assessed by paediatrician or clinical psychologist in our service before their clinical diagnosis was arrived.

However, as majority of patients were referred to our service between age 2 to 4 years, the findings of comorbid ADHD in ASD group in our setting seem to be at a lower end of the range compared to studies in other settings. Furthermore, the update information from Child Psychiatric Clinics in Hospital Authority was not retrieved as we did not obtain consent for such in our current study. More detailed information regarding the family history of substance abuse, the type of illicit drug use; and the family history of ADHD in parents were limited in the medical records. Improvement in documentation in these aspects should be emphasized in our medical records and if further studies would be performed in the future.

Conclusion

To the best of our knowledge, this is the first multi-center study in Hong Kong reporting the comorbidity rate of ASD in ADHD children and vice versa, we have also compared the clinical profile and characteristics between children with single diagnosis and dual diagnosis in our setting. Based on the new information from our study, we move a step forward in having a better understanding in children with these two common yet complicated neurodevelopmental disorders. More recognition among clinicians on the common comorbidity of both conditions is essential. Moreover, increased awareness of clinicians to screen for ADHD features in developmental-behavioral assessment especially in children with a family history of ADHD and/or substance abuse would be beneficial. Timely identification of the comorbidity can facilitate the formulation of a holistic management plan and care for these children and their families. Teachers and therapists could set education and training plans that fit their complex needs. In addition, Methylphenidate prescription should be more carefully monitored by doctors when treating children with dual diagnosis.

Declaration of Interest

We declare that we have no conflict of interest.

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