Introduction
Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed neurodevelopmental disorder of childhood, and it is associated with social and academic difficulties and psychiatric comorbidities such as depression, anxiety, low self-esteem, and pervasive across settings can cause problems in the daily activities of a child as well as later in their adult life1. In addition, studies detected difficulties in behavioral regulation and emotional stability in children younger than 2 years of age who were later diagnosed diagnosis with ADHD2. ADHD during childhood is one of the most common causes of school failure and social problems. It is a disorder that can persist and manifest in adulthood in more than 60% of cases. Several studies have found that the quality of life in adolescents and in adults who were diagnosed with ADHD during their childhood is clearly related to the severity of comorbidities symptoms3. In studies with adults who have a residual form of this disorder, the research has found a higher frequency of behavioral abnormalities in labor activities and in family relationships, substance abuse, accidents, and crime4. Depression during childhood and adolescence also predicts negative outcomes in adulthood such as stressful life events, low social support, and low satisfaction with life5. Maternal depression and concurrent symptoms at 4-6 years of age predict which children with ADHD are at greatest risk for depression and/or suicidality as adolescents6. A diagnosis of both ADHD and depression is associated with the most significant deficiencies for either disorder than one alone. For example, young people with ADHD and depression have an increased risk of developing bipolar disorder and oppositional defiant disorder, and require much more intensive interventions compared to young people with ADHD but without depression5. Interventions for both diagnoses also report more psychosocial and family problems as well as higher levels of stress7,8. Despite the impact of ADHD and depressive symptoms in young people, few studies have examined the underlying mechanisms which contribute to the emergence of these symptoms9. One promising mechanism is emotion regulation (ER), as the deficit in the ability of ER has been associated with young children with ADHD and with depressive symptoms. This point is primarily relevant for young people with ADHD symptoms as it emphasizes the role of effort in control - the deliberate modulation of emotional states, emotional regulation, and subsequent behaviors, which involve the ability to focus deliberately, divert attention, hyperactivity, and inhibit or activate an appropriate behavior10-12. Several studies suggest that young people with ADHD demonstrate an inability to continue a task when frustrated or they have an inability to seek help from their parents. In extreme levels, when they are solving more limited problems, they focus more on negative aspects of a task compared to healthy controls. Young people with ADHD also have difficulties identifying and processing negative emotions and high-stress exposure between childhood and young adulthood is strongly intertwined with a persistent course of ADHD and with comorbid problems taking the form of severe and persistent emotion dysregulation (irritability, extreme reactivity, and frustration) or elevated and increasing irritability, anxiety, and depression13,14. Longitudinal research has shown that the ADHD diagnosis persists into adulthood, participants manifest higher levels of impulsive emotions (defined by symptoms such as low tolerance to frustration, impatience, and irritability) compared to those who do not have ADHD as an adult. This situation contributes to deficits in family, peer, financial, and labor relationships15. When comparing subtypes, children with inattentive ADHD have a higher rate in eating disorders, anxiety, and depression than in those with hyperactive and/or combined ADHD. In this both hyperactive and combined ADHD, children often have social problems, as they take things that do not belong to them, do not wait their turn, and act without considering before the feelings of others. Children with ADHD inattentive type, rather, tend to be socially isolated, self-absorbed, and most likely have an introverted behavior16 (Diamond, 2005). ADHD without hyperactivity and ADHD with hyperactivity are two different disorders with different cognitive and behavioral profiles, different patterns of comorbidities, different responses to medication, and different underlying neurobiology16 characteristics that become chronic and progressively worse (i.e., findings support the diagnosis of ADHD in younger children by demonstrating that the symptoms and associated impairment are likely to persist well into elementary school)17. It is unclear whether the features of anxiety and ADHD are possible to identify very early of age; for example, in one child, his emotional deregulation at 18 months of age was associated with symptoms of anxiety and ADHD at 3 years of age. The study could not confirm if the emotional deregulation at 18 months predicts the cooccurrence of anxiety and ADHD symptoms. This implies that the identification risk at 18 months is a clinical challenge. By identifying early, there is a risk of over-identification and treatment of preschool children who are not going to develop ADHD or anxiety in their immediate future18. However, longitudinal studies in school-age children found continuity of symptoms for anxiety and ADHD19,20. In children with ADHD with an anxiety disorder have more than 50% of them also oppositional defiant disorder or conduct disorder21.
The relationship between ADHD and sleep disorders is unclear. According to a categorical approach, specific sleep disorders are a common comorbidity in children with ADHD. Those with ADHD more often display hypopnea and/or apnea, movements in peripheral limbs during sleep, insomnia, and narcolepsy which could result in significant functional impairments that affect mood, attention, behavior, and ultimately school/work performance and quality of life22. Polysomnography shows an increased latency in sleep onset of families ADHD children report less maintenance and duration of sleep, resistance by the child at bedtime, difficulties in sleep onset, difficult in nocturnal breathing, enuresis, nocturnal awakenings, and difficulty in waking up in the morning and daytime sleepiness23. In another multicenter cross-sectional study in 12 Spanish hospitals, neurologists reported that sleep disorder affects less than a quarter of patients (24.5%) and up to 23% stated that the prevalence was < 10%, while between 58% and 92% of parents of patients attending consultations in pediatric neurology report that their children have some aspect disturbed in the sleep. Although most neurologists appreciate the importance of diagnosis and treatment of sleep disorders in children with neurological disorders, it is often underestimated and therefore essential to include in ADHD evaluations as proper and early treatment would improve symptoms and the quality of life in patients and families24.
Moreover, many children with ADHD develop epilepsy. In one study of 23 patients with epilepsy, 19 of them had ADHD symptoms preceding the onset of seizures25. An epidemiological study showed that the risk of epilepsy is 2.5 times higher in children who have already developed symptoms of ADHD26. With regard to abnormal electroencephalographic (EEG) recordings outside epilepsy, a recent study found abnormal EEG readings in 19 of 50 children diagnosed with ADHD. The most abnormal results were in focal and generalized paroxysms of sharp waves in phase opposition and slow waves. The most frequent location of EEG abnormalities was in the temporal lobe (45%), although there were focal paroxysms in other lobes; 28% in the right temporal region, 17% in the left temporal region, and 22% in the left frontal lobe, followed by 11% in the left parietal region27.
In children's ADHD diagnosis, enuresis is a relatively new clinical aspect and is part of our ongoing effort to better understand comorbidities. Children with ADHD are more likely than their peers without ADHD to develop enuresis with a similar trend for encopresis and comorbid enuresis implying an immaturity in the developing nervous system of children who have this combination of problems28. Children with primary nocturnal enuresis (PNE) show a significant reduction in activity in the left posterior cerebellum compared to controls without PNE29. Similarly, functional magnetic resonance imaging (fMRI) demonstrated low activation in the right prefrontal cortex and increased activity in the left hemisphere during inhibition of motor response compared to controls without PNA, indicating abnormal network brain areas during response inhibition in children with PNE30.
Therefore, this study aims to characterize the diagnostic complexity of children and adolescents who receive a diagnosis of ADHD. These findings could be helpful to develop guidelines that reflect the needs of children with ADHD. We treat a review of the comorbidities in itself complex in the diagnosis of ADHD.
Methods
Participants
Retrospective analysis of a clinical database (CDB) was conducted identifying 1049 Spanish children and adolescents diagnosed with ADHD according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) in the Department of Pediatrics of the Hospital Universitario Dr. Peset. The comorbidities were diagnosed in the corresponding medical service (Pediatrics, Mental Health, Neurology). Personal and clinical data of patients were reviewed to determine those who met the clinical criteria previously established and described below. After eliminating patients who did not meet for the above, 297 CDB aged 6-16 years of children (79 females and 218 males; mean age, 09.10 years) diagnosed with ADHD were used for this study.
Exclusion criteria
- Patients diagnosed with ADHD born and raised from January 1999 to December 2009 in Spain with IQ below 80.
- Patients aged in or outside the range 6-15 years and 11 months adopted or born and raised in Spain of foreign parents
- Patients diagnosed with ADHD who not attended medical appointments.
- Patients diagnosed with ADHD who later acquired brain injury, surgery, and/or neurological diseases such as traumatic brain injury, epilepsy, and/or Gilles de la Tourette Syndrome (Table 1).
226 participants born since 1990 and 1998 |
379 participants without an interdisciplinary diagnosis |
14 participants had ADS |
47 participants had a neurological disease diagnosed as epilepsy, brain traumatic |
9 participants had a genetic syndrome diagnosed as deletions |
26 participants coming from national or international adoptions or born in Spain of foreign parents |
39 participants had not neurophysiological studies (EEG, qEEG, and ERPs) |
12 participants without approach less medical data |
Total included |
297 participants met the clinical criteria |
ADS: autism spectrum disorder; EEG: electroencephalographic; qEEG: quantitative EEG; ERPs: event-related potentials.
In the following table are described by the participants:
Medical data related to the child were recorded in a confidential database for exclusive use of the project. Data about diagnosis, treatments, personal circumstances, and about clinical evolution were collected according to the law 15/99 on protection of personal data.
Statistical analysis
First, descriptive statistics as comorbidity prevalence of the different pathologies studies and their confidence interval 95% were calculated. The relationships between the categorical variables the prevalence of ADHD child's comorbidity with the ADHD child's without comorbidity were analyzed using the Chi-square test (p < 0.05) by each comorbidity studied. Finally, a comparison of each comorbidity prevalence identify was also compared through the review of outside studies from other countries; it was analyzed using the Chi-square test (p < 0.05). Statistical analyses were conducted using IBM SPSS Statistics 25.
Results
Many children diagnosed with ADHD have comorbidities. In Spain, children and adolescents diagnosed with ADHD, the current study found that all potential comorbid conditions were statistically significant in the aspects analyzed (p ≤ 0.001) (Table 2). When examining outside studies, results on the presence or absence of conditions that coexist in children diagnosed with ADHD outside of Spain are statistically significant in all aspects analyzed (p ≤ 0.001), except in anxiety, and in Asperger's disease31 and in female and male Enuresis32 (Table 2a).
Variable | Frequency (n) | Prevalence (%) | Prevalence (95% CI) | Chi-square test (p) |
---|---|---|---|---|
Peer/dyadic relationship difficulties | 74 | 25.00 | 20.18-30.31 | ≤ 0.001 |
Depression/anxiety | 83 | 28.00 | 23.62-34.18 | ≤ 0.001 |
Anxiety | 41 | 14.00 | 10.48-18.74 | |
Sleep disorders | 56 | 18.90 | 15.87-25.31 | ≤ 0.001 |
Insomnia for lack of limits on family | 7 | 2.35 | 1.25-5.44 | ≤ 0.001 |
Nocturnal enuresis | 15 | 5.10 | 2.95-8.36 | ≤ 0.001 |
Snorer | 3 | 1.01 | 0.26-3.17 | ≤ 0.001 |
Nighttime awakenings | 11 | 3.70 | 1.95-6.71 | ≤ 0.001 |
Delay sleep onset syndrome | 3 | 1.01 | 0.26-3.17 | ≤ 0.001 |
Restless leg syndrome | 3 | 1.01 | 0.26-3.17 | ≤ 0.001 |
Bruxism | 3 | 1.01 | 0.26-3.17 | ≤ 0.001 |
Catathrenia (night whimper) | 4 | 1.70 | 0.43-3.64 | ≤ 0.001 |
Night terrors | 2 | 0.70 | 0.11-2.67 | ≤ 0.001 |
Somniloquy | 5 | 1.70 | 0.62-4.10 | ≤ 0.001 |
Epilepsy (EEG) | 72 | 24.35 | 19.69-29.79 | ≤ 0.001 |
Primary nocturnal enuresis | 10 | 3.37 | 1.72-6.29 | |
Female | 2 | 0.67 | 0.11-2.67 | |
Male | 8 | 2.70 | 1.25-5.44 | 0.055 |
ANOVA test: p < 0.01. RF: relative frequency; %: proportion; 95% CI: Confidence Interval 95%; p: Fisher values; EEG: encephalogram.
Variable | Frequency (n) | Prevalence (%) | Prevalence (95% CI) | Chi-square test (p) | Previous studies |
---|---|---|---|---|---|
Peer/dyadic relationship difficulties | 92 | 56.00 | 47.83-63.41 | ≤ 0.001 | Hoza, 2005 |
Depression | 10 | 6.70 | 3.59-12.82 | 0.029 | Bauermeister, 2007 |
Depression | 68 | 21.30 | 17.03-23.30 | 0.020 | Silva, 2015 |
Anxiety | 34 | 23.77 | 17.23-31.75 | 0.012 | Bauermeister, 2007 |
Anxiety | 169 | 52.60 | 47.34-58.54 | ≤ 0.001 | Silva, 2015 |
Anxiety | 12 | 11.90 | 6.55-20.20 | 0.665 | Ogrim, 2012 |
Asperger syndrome (symptoms) | 5 | 4.95 | 1.83-11.71 | 0.148 | Ogrim, 2012 |
Sleep disorders | 45 | 31.46 | 24.10-39.84 | 0.003 | Bauermeister, 2007 |
Epilepsy 6-18 years old (EEG) | 2843 | 15.63 | 15.10-16.17 | ≤ 0.001 | Chou, 2013 |
Epilepsy 8-11 years old (EEG) | 3 | 10.00 | 2.61-27.67 | 0.095 | Fonseca, 2008 |
Primary nocturnal enuresis | 100 | 9.00 | 7.25-10.63 | 0.044 | Shreeram, 2009 |
Female | 32 | 2.51 | 1.95-4.00 | 0.198 | |
Male | 68 | 6.21 | 4.70-7.56 | 0.216 | |
Primary nocturnal enuresis | 35 | 12.10 | 6.99-13.45 | ≤ 0.001 | Mellon, 2013 |
Primary nocturnal enuresis | 165 | 17.60 | 15.02-19.94 | 0.010 | Joinson, 2007 |
ANOVA test: p < 0.01 (11, 20, 8, 33, 34, 28, 35); p ≤ 0.05 (31, 32). RF: relative frequency; %: proportion; 95% CI: Confidence Interval 95%; p: Fisher values;
EEG: electroencepham.
Discussion
In this study in ADHD, 25% of patients showed social problems, 28% depression and/or anxiety, and 19% had difficulties in the maintenance of nighttime sleep. The results were associated with those obtained by Hoza12, Mellon28, and Sheerman32 in United States of America, by Chou in China33, by Fonseca in Brazil34, by Joinson in United Kingdom35, by Silva in Australia9, and by Bauermeister in Puerto Rico20.
Children with ADHD often have conflicts with adults and peers, and suffer from unpopularity, rejection by peers, and a lack of friendships, in part as a consequence of their ADHD symptoms. In summary, social relations are also one of the biggest problems in children with ADHD. Parents, teachers, and their own colleagues systematically report that those with ADHD can be aggressive, intrusive, disruptive, manipulative, and less able to communicate and socialize effectively11,13,36. Some studies reported little difference and related problems between genders20.
Parents with ADHD children compared with normative data reported more problems in terms of emotional-behavioral role function, behavior, mental health, and self-esteem. Children with multiple comorbidity disorders have poorer psychosocial health-related quality of life across a range of domains compared with children with none and one comorbid disorder4. In addition, compared to children who have no comorbidities, psychosocial health-related quality of life was significantly lower in children with comorbid oppositional defiant disorder or conduct disorder, but not in children with a comorbid learning disorder4. In summary, social relations are one of the biggest problems in children with ADHD.
Sleep disorders may also induce symptoms of ADHD and are believed to be the result of excessive daytime sleepiness. However, it may be difficult for the clinical professional to recognize differences between the comorbidity from one sleep disorder to similar symptoms in ADHD37,38. We found abnormal results in 24.35% of patients; therefore, the EEG is a valid study in the valuation process for test underlying or comorbid epilepsy in children with ADHD. Epilepsy and ADHD can affect social, educational, and emotional life. The association between ADHD and epilepsy is of great interest in many studies published recently because children with epilepsy have a significant risk in presenting ADHD, and often display deficits in the performance of working memory26,33,39. Studies have detected significant similarities between epilepsy and ADHD in males (citation). ADHD with or without epilepsy may share a common abnormal and underlying neurobiological cause40.
In our study, the PNE in children with ADHD was in 5.05%, we consider the increase of psychological problems reported by parents of children with enuresis compared to those children without enuresis, and the possible pathogenic etiological between ADHD and incontinence according to neurophysiological and neuroimaging results30. However, enuresis is difficult to treat and show lower compliance. Given results in the treatment in incontinence are appreciated in the relevant clinical data regarding ADHD and enuresis, this appears to be a main comorbid condition that should be evaluated and specifically address in ADHD children40.
Conclusions
The current study carried out a broad and comprehensive characterization of comorbidities in children and adolescents with ADHD in an effort to promote appropriate clinical decision making and reduced confusion. Detection and resolution of depressive symptoms, anxious symptoms, and/or difficulties in sleep in those diagnosed with ADHD may reduce emotional risk and morning fatigue. It is very important to detect these symptoms to decrease social and cognitive consequences. Finally, using EEG in this population provides greater assessment and diagnosis of complex developmental disorders such as ADHD.
Study limitations
First, we recruited data about ADHD comorbidities from different medical specialties departments at the hospital. Our findings should be interpreted in light of limitations. Accordingly, we were unable to stratify symptoms according to high- and low-comorbidity. Second, we were not able to test whether comorbidities are unique to children with ADHD or are also observed in other disorders such as depression and learning delay. Future studies are needed about the relationship between comorbidities and ADHD.