Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in adult psychiatry. A 20-year register study

Abstract

Nylander L, Holmqvist M, Gustafson L, Gillberg C. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in adult psychiatry. A 20-year register study. Nord J Psychiatry 2012;Early Online:1–7 Objective: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are increasingly recognized in adults. This study aimed to assess trends in diagnostic practice, diagnostic delay and comorbidity regarding ADHD and ASD in adult psychiatric patients. Methods: Individuals with diagnosed ADHD or ASD were identified in an adult psychiatry register comprising 56,462 patients. Results: ADHD was diagnosed in up to 2.7% and ASD in 1.3% of the patients. Most cases were diagnosed within 2 years of first contact with adult psychiatry, but some patients were treated for 10 years or more before being diagnosed with ADHD or ASD. Seventy per cent of ADHD and 56% of ASD patients were treated as outpatients only. Other psychiatric diagnoses were registered in about 60%. Affective disorders were common in patients with ADHD. Psychoses and intellectual disability were more common in ASD patients. Psychoactive substance use-related disorders were considerably more common in those with ADHD. Concomitant ADHD and ASD were seldom diagnosed in this clinical material. Conclusion: ADHD and ASD were probably much underdiagnosed in the studied group of psychiatric patients. Other psychiatric diagnoses were common, but not ADHD with concomitant ASD.     

Temporal and probabilistic discounting of rewards in children and adolescents: effects of age and ADHD symptoms

This study investigated whether age and ADHD symptoms affected choice preferences in children and adolescents when they chose between (1) small immediate rewards and larger delayed rewards and (2) small certain rewards and larger probabilistic uncertain rewards. A temporal discounting (TD) task and a probabilistic discounting (PD) task were used to measure the degree to which the subjective value of a large reward decreased as one had to wait longer for it (TD), and as the probability of obtaining it decreased (PD). Rewards used were small amounts of money. In the TD task, the large reward (10 cents) was delayed by between 0 and 30s, and the immediate reward varied in magnitude (0-10 cents). In the PD task, receipt of the large reward (10 cents) varied in likelihood, with probabilities of 0, 0.25, 0.5, 0.75, and 1.0 used, and the certain reward varied in magnitude (0-10 cents). Age and diagnostic group did not affect the degree of PD of rewards: All participants made choices so that total gains were maximized. As predicted, young children, aged 6-11 years (n = 25) demonstrated steeper TD of rewards than adolescents, aged 12-17 years (n = 21). This effect remained significant even when choosing the immediate reward did not shorten overall task duration. This, together with the lack of interaction between TD task version and age, suggests that steeper discounting in young children is driven by reward immediacy and not by delay aversion. Contrary to our predictions, participants with ADHD (n = 22) did not demonstrate steeper TD of rewards than controls (n = 24). These results raise the possibility that strong preferences for small immediate rewards in ADHD, as found in previous research, depend on factors such as total maximum gain and the use of fixed versus varied delay durations. The decrease in TD as observed in adolescents compared to children may be related to developmental changes in the (dorsolateral) prefrontal cortex. Future research needs to investigate these possibilities.     

Neural mechanisms of negative reinforcement in children and adolescents with autism spectrum disorders

Background

Previous research has found accumulating evidence for atypical reward processing in autism spectrum disorders (ASD), particularly in the context of social rewards. Yet, this line of research has focused largely on positive social reinforcement, while little is known about the processing of negative reinforcement in individuals with ASD.

Methods

The present study examined neural responses to social negative reinforcement (a face displaying negative affect) and non-social negative reinforcement (monetary loss) in children with ASD relative to typically developing children, using functional magnetic resonance imaging (fMRI).

Results

We found that children with ASD demonstrated hypoactivation of the right caudate nucleus while anticipating non-social negative reinforcement and hypoactivation of a network of frontostriatal regions (including the nucleus accumbens, caudate nucleus, and putamen) while anticipating social negative reinforcement. In addition, activation of the right caudate nucleus during non-social negative reinforcement was associated with individual differences in social motivation.

Conclusions

These results suggest that atypical responding to negative reinforcement in children with ASD may contribute to social motivational deficits in this population.     

A comparison of tantrum behavior profiles in children with ASD,ADHD and comorbid ASD and ADHD

The present study was conducted to compare rates of tantrum behaviors in children with autism spectrum disorders (ASD) (n = 255), attention-deficit/hyperactivity disorder (ADHD) (n = 40) and children with comorbid ASD and ADHD (n = 47). Parents/guardians of children aged 3–16 years were surveyed about their children's behaviors using the Autism Spectrum Disorders-Comorbidity for Children (ASD-C-C). Children with ADHD alone differed from children with ASD alone and children with comorbid ASD and ADHD on rates of tantrum behaviors. Examination of individual tantrum behavior items indicated that children with comorbid ASD and ADHD have a more similar symptom presentation to children with ASD than children with ADHD. This study adds to the literature on the presentation of common co-occurring behaviors of ASD when there is comorbid ADHD. The implications of these findings may aid in the assessment and treatment of tantrum behaviors in children with comorbid ASD and ADHD.     

Autism spectrum disorder symptoms in children with ADHD: A community-based study

This study examined the prevalence of autism spectrum disorder (ASD) symptoms in a community-based sample of children with attention-deficit/hyperactivity disorder (ADHD) and non-ADHD controls. We also examined the relationship between ASD symptoms and ADHD subtype, ADHD symptom severity and child gender. Participants were 6–10-year-old children (164 ADHD; 198 non-ADHD control) attending 43 schools in Melbourne, Australia, who were participating in the Children's Attention Project. ADHD was assessed in two stages using the parent and teacher Conners’ 3 ADHD index and the Diagnostic Interview Schedule for Children IV (DISC-IV). ASD symptoms were identified using the Social Communication Questionnaire (SCQ). Unadjusted and adjusted linear and logistic regression examined continuous and categorical outcomes, respectively. Children with ADHD had more ASD symptoms than non-ADHD controls (adjusted mean difference = 4.0, 95% confidence interval (CI) 2.8; 5.3, p < 0.001, effect size = 0.7). Boys with ADHD had greater ASD symptom severity than girls with ADHD (adjusted mean difference = 2.9, 95% CI 0.8; 5.2, p = 0.01, effect size = 0.4). Greater ADHD symptom severity was associated with greater ASD symptom severity (regression co-efficient = 1.6, 95% CI 1.2; 2.0, p < 0.001). No differences were observed by ADHD subtype. Greater hyperactive/impulsive symptoms were associated with greater ASD symptoms (regression coefficient = 1.0; 95% CI 0.0; 2.0, p = 0.04) however, this finding attenuated in adjusted analyses (p = 0.45). ASD symptoms are common in children with ADHD. It is important for clinicians to assess for ASD symptoms to ensure appropriate intervention.     

Rates of comorbid symptoms in children with ASD,ADHD, and comorbid ASD and ADHD

The current diagnostic criteria do not allow co-diagnosis of autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). As a result, there has been little research on how these two disorders co-occur in the ASD population. The current study aimed to extend the literature in this area by examining comorbid rates in three different diagnostic groups (ASD, ADHD, and comorbid ASD + ADHD) using the Autism Spectrum Disorders-Comorbidity for Children (ASD-CC). Children with comorbid ASD and ADHD evinced higher rates of comorbid symptoms than children with ASD or ADHD alone. Additionally, children with comorbid ASD and ADHD endorsed more severe comorbid symptoms. Implications regarding these findings are discussed.     

Effortful control in typically developing boys and in boys with ADHD or autism spectrum disorder

Despite increased interest in the role of effortful control (EC) in developmental disorders, few studies have focused on EC in autism spectrum disorders (ASD) and no study so far has directly compared children with ASD and children with ADHD. A first aim of this study was to investigate whether typically developing (TD) boys, boys with ADHD and boys with ASD can be differentiated based on EC levels. A second aim was to evaluate the relationship between EC and symptoms of ADHD and ASD. We assessed EC in 27 TD boys, 27 boys with ADHD and 27 boys with ASD (age 10-15) using different EC questionnaires. Clinical groups scored lower than the TD group on all EC total scales, but could only be differentiated from each other by means of self-reported persistence, impulsivity and activation control. Our data suggest that although EC is useful in differentiating TD boys from clinical groups, it is less efficient in distinguishing ADHD from ASD. Also, results suggest that EC plays a role in the manifestation of symptoms of both ADHD and ASD and that high levels of EC enable children to function more adequate in daily situations.     

Using the DBC-P Hyperactivity Index to screen for ADHD in young people with autism and ADHD: A pilot study

This study aimed to (1) determine preliminary validity of the Developmental Behaviour Checklist-Hyperactivity Index (DBC-HI) as a screening measure of combined-type ADHD in autism and ADHD, and (2) compare emotional-behavioural disturbance using the DBC in autism, ADHD and autism + ADHD. Forty-nine age- and PIQ-matched young people [6–18 years; 12 autism, 13 ADHD, 12 autism + ADHD, 12 typically developing] were recruited. Parents completed the Conners-Revised Rating Scale and DBC. The DBC-HI displayed strong internal consistency and good external validity, reliably measuring combined-type ADHD. The DBC-HI distinguished autism from autism + ADHD with fair sensitivity and specificity. Individuals with autism + ADHD exhibited a more severe profile of emotional-behavioural disturbance than autism or ADHD alone. The DBC may be a useful ‘all-in-one’ screening tool to (1) identify comorbidity and (2) determine the severity of emotional-behavioural disturbance in autism and/or ADHD.     

Studying the relation between temporal reward discounting tasks used in populations with ADHD: A factor analysis

Background: This study aimed at investigating the relationship between tasks that have been used in attention deficit hyperactivity disorder (ADHD) to measure choices between smaller immediate and larger delayed rewards: real and hypothetical temporal discounting tasks, and single‐choice paradigms. Methods: Participants were 55 undergraduate psychology students. Tasks included a real and hypothetical version of a temporal discounting (TD) task with choices between a large reward (10 cents) after delays up to 60 seconds, and smaller immediate rewards (2–8 cents); two versions of a hypothetical temporal discounting task with choices between a large reward ($100) after delays up to 120 months, and smaller immediate rewards ($1–$95); a Choice Delay Task with choices between one point now and two points after 30 seconds (one point is worth five cents). Results: Correlation analyses showed that the real and the hypothetical TD tasks with 10 cents were very strongly associated. However, the hypothetical TD tasks with $100 did not correlate with either the real or the hypothetical TD task with 10 cents. Principal component analysis extracted two components: one for small amounts and short delays, and a second one for large rewards and long delays. Conclusions: Temporal reward discounting is not a uniform construct. Functional brain imaging research could shed more light on unique brain activation patterns associated with different forms of temporal reward discounting. Copyright © 2010 John Wiley & Sons, Ltd.     

A multisite trial of atomoxetine and parent training in children with autism spectrum disorders: Rationale and design challenges

Several randomized controlled trials (RCTs) involving children with autism spectrum disorder (ASD) have examined effectiveness of mono-therapies for problem behavior. However, results have not been as encouraging as in typically developing children. For example, when prescribed stimulants, children with ASD and hyperactivity/inattentiveness, show only moderately reduced symptoms, with frequent side effects. Therefore, alternative treatments or combinations of treatments are needed. The Children's Hyperactivity and Autism Research Treatment Study (CHARTS) is a randomized clinical trial comparing the individual and combined effects of atomoxetine and parent training to treat hyperactivity, inattentiveness, and noncompliance in children with ASD. Design challenges included the overall study design, targeting of different outcomes by different treatments, and data analysis. This article details options for addressing a number of these methodological issues in the context of conducting a large multicenter RCT with an ASD population.     

Uniqueness of action monitoring in children with autism spectrum disorder: Response types and temporal aspects

Background: Action monitoring, the process for evaluating the appropriateness of one’s own actions, is reported to be atypical in individuals with autism spectrum disorder (ASD). Method: We examined the characteristics of action monitoring in 11 children with ASD and 12 children with typical development (TD), analyzing stimulus-locked and response-locked event-related potential components (i.e., N2; error-related negativity, ERN; and error positivity, Pe) related to execution of a flanker task. Results: We found a smaller N2 amplitude in children with ASD than in those with TD. Children with ASD also had a larger amplitude of ERN for partial error responses (electromyographic activity corresponding to the inappropriate hand side before response execution) than did children with TD. Additionally, the ERN amplitude for the partial error response was correlated with the Autistic Mannerisms of the Social Responsiveness Scale. There were no significant differences in Pe amplitudes between children with ASD and those with TD. Conclusion: The results suggest that action monitoring in children with ASD is significantly different both before and after response execution. We hypothesized that the detail-focused processing style of ASD reduces the demands of action monitoring before response execution; however, autistic mannerisms evoke excessive concern regarding trivial mistakes after response execution.     

Correlation between EEG abnormalities and symptoms of autism spectrum disorder (ASD)

Children with ASD often suffer from epilepsy and paroxysmal EEG abnormality. Purposes of this study are the confirmation of incidence of epileptic seizures and EEG abnormalities in children with autism using a high performance digital EEG, to examine the nature of EEG abnormalities such as locus or modality, and to determine if the development of children with ASD, who have experienced developmental delay, improves when their epilepsy has been treated and maintained under control. A total of 1014 autistic children that have been treated and followed-up for more than 3 years at Yasuhara Children’s Clinic in Osaka, Japan, were included in this study. Each participant’s EEG had been recorded approximately every 6 months under sleep conditions. Epilepsy was diagnosed in 37% (375/1014) of the study participants. Almost all patients diagnosed with epilepsy presented with symptomatic epilepsy. The data showed that the participants with lower IQ had a higher incidence of epileptic seizures. Epileptic EEG discharges occurred in 85.8% (870/1014) of the patients. There was also a very high incidence of spike discharges in participants whose intellectual quotient was very low or low. Epileptic seizure waves most frequently developed from the frontal lobe (65.6%), including the front pole (Fp1 and Fp2), frontal part (F3, F4, F7 and F8) and central part (C3, Cz and C4). The occurrence rate of spike discharges in other locations, including temporal lobe (T3, T4, T5, T6), parietal lobe (P3, Pz, P4), occipital lobe (O1, O2) and multifocal spikes was less than 10%. These results support the notion that there is a relationship between ASD and dysfunction of the mirror neuron system. The management of seizure waves in children diagnosed with ASD may result in improves function and reduction of autistic symptoms.     

Association of dopamine gene variants,emotion dysregulation and ADHD in autism spectrum disorder

The aim of the present study was to evaluate the association of dopaminergic gene variants with emotion dysregulation (EMD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD). Three dopamine transporter gene (SLC6A3/DAT1) polymorphisms (intron8 5/6 VNTR, 3′-UTR 9/10 VNTR, rs27072 in the 3′-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on à priori evidence of regulatory activity or, in the case of DAT1 9/10 VNTR, commonly reported associations with ADHD. A sample of 110 children with ASD was assessed with a rigorously validated DSM-IV-referenced rating scale. Global EMD severity (parents’ ratings) was associated with DAT1 intron8 (ηp² = .063) and rs2283265 (ηp² = .044). Findings for DAT1 intron8 were also significant for two EMD subscales, generalized anxiety (ηp² = .065) and depression (ηp² = .059), and for DRD2 rs2283265, depression (ηp² = .053). DRD2 rs2283265 was associated with teachers’ global ratings of ADHD (ηp² = .052). DAT1 intron8 was associated with parent-rated hyperactivity (ηp² = .045) and both DAT1 9/10 VNTR (ηp² = .105) and DRD2 rs2283265 (ηp² = .069) were associated with teacher-rated inattention. These findings suggest that dopaminergic gene polymorphisms may modulate EMD and ADHD symptoms in children with ASD but require replication with larger independent samples.     

Externalizing and tantrum behaviours in children with ASD and ADHD compared to children with ADHD

Objective: Compare rates of externalizing in children with autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) symptoms to children with ADHD.

Method: Parents/caregivers of 85 children with ASD and/or ADHD were surveyed about their children's behaviours using the Autism Spectrum Disorders-Comorbidity for Children and the Autism Spectrum Disorders-Behaviour Problem for Children.

Results: Specific main effects analyses were then conducted. Children with ASD exhibited a higher number of externalizing (F(1,?83)?=?83.34, p?<?0.001) and tantrum behaviours (F(1,83)?=?781.86, p?<?0.001) than children without ASD.

Conclusions: ASD exacerbates the externalizing symptoms of ADHD during childhood. This study adds to the literature on the importance of assessing for a wide-range of possible behaviour problems in children presenting with ADHD symptomatology. The implications of these findings are discussed in the context of other research.     

Disruptive behavior disorders in children and adolescents with autism spectrum disorders: A review of the prevalence,presentation, and treatment

Children and adolescents with autism spectrum disorders (ASDs) often exhibit behaviors consistent with a disruptive behavior disorder (DBD) such as oppositional defiant disorder (ODD) or conduct disorder (CD). Understanding the relationship between ASDs and DBDs has important implications for clinicians and researchers. We reviewed 55 peer-reviewed articles published between 2000 and 2012 on the prevalence, phenomenology, or psychosocial treatments of DBDs in youth with ASDs. Prevalence estimates vary between 4% and 37% for ODD and 1% and 10% for CD. On the whole, approximately one in four children with an ASD meets diagnostic criteria for either ODD or CD. Most research on phenomenology has focused on distinguishing between DBDs and ASDs, rather than examining their co-occurrence. After the preschool years, the disorders can be reliably distinguished, but certain behaviors are more common among those with ASDs compared to their non-ASD counterparts. If one excludes medication trials and single-subject designs, there have been few treatment studies on DBDs in ASDs. Parent training has been the primary mode of psychosocial treatment and has some support for its efficacy. Overall, when it comes to DBDs, there has been a dearth of research using DSM-nosology in youth with ASDs.     

Multimodal emotion processing in autism spectrum disorders: An event-related potential study

This study sought to describe heterogeneity in emotion processing in autism spectrum disorders (ASD) via electrophysiological markers of perceptual and cognitive processes that underpin emotion recognition across perceptual modalities. Behavioral and neural indicators of emotion processing were collected, as event-related potentials (ERPs) were recorded while youth with ASD completed a standardized facial and vocal emotion identification task. Children with ASD exhibited impaired emotion recognition performance for adult faces and child voices, with a subgroup displaying intact recognition. Latencies of early perceptual ERP components, marking social information processing speed, and amplitudes of subsequent components reflecting emotion evaluation, each correlated across modalities. Social information processing speed correlated with emotion recognition performance, and predicted membership in a subgroup with intact adult vocal emotion recognition. Results indicate that the essential multimodality of emotion recognition in individuals with ASDs may derive from early social information processing speed, despite heterogeneous behavioral performance; this process represents a novel social-emotional intervention target for ASD.     

The relationship between sleep and behavior in autism spectrum disorder (ASD): a review

Although there is evidence that significant sleep problems are common in children with autism spectrum disorder (ASD) and that poor sleep exacerbates problematic daytime behavior, such relationships have received very little attention in both research and clinical practice. Treatment guidelines to help manage challenging behaviors in ASD fail to mention sleep at all, or they present a very limited account. Moreover, limited attention is given to children with low-functioning autism, those individuals who often experience the most severe sleep disruption and behavioral problems. This paper describes the nature of sleep difficulties in ASD and highlights the complexities of sleep disruption in individuals with low-functioning autism. It is proposed that profiling ASD children based on the nature of their sleep disruption might help to understand symptom and behavioral profiles (or vice versa) and therefore lead to better-targeted interventions. This paper concludes with a discussion of the limitations of current knowledge and proposes areas that are important for future research. Treating disordered sleep in ASD has great potential to improve daytime behavior and family functioning in this vulnerable population.     

Temporal discounting for self and friends in adolescence: A fMRI study

Adolescence is characterized by impulsivity but also by increased importance of friendships. This study took the novel perspective of testing temporal discounting in a fMRI task where choices could affect outcomes for 96 adolescents (aged 10–20-years) themselves and their best friend. Decisions either benefitted themselves (i.e., the Self Immediate – Self Delay’ condition) or their friend (i.e., ‘Friend Immediate – Friend Delay’ condition); or juxtaposed rewards for themselves and their friends (i.e., the ‘Self Immediate – Friend Delay’ or ‘Friend Immediate – Self Delay’ conditions). We observed that younger adolescents were more impulsive; and all participants were more impulsive when this was associated with an immediate benefit for friends. Individual differences analyses revealed increased activity in the subgenual anterior cingulate cortex extending in the ventral striatum for immediate relative to delayed reward choices for self. Temporal choices were associated with activity in the prefrontal cortex, parietal cortex, insula, and ventral striatum, but only activity in the right inferior parietal lobe was associated with age. Finally, temporal delay choices for friends relative to self were associated with increased activity in the temporo-parietal junction and precuneus. Overall, this study shows a unique role of the social context in adolescents’ temporal decision making.     

A pilot study of combining social skills training and parenting training for children with autism spectrum disorders and their parents in Japan

The purpose of this study is to investigate the effects of a program containing a combination of social skills training (SST) and parenting training (PT) for the enrichment of social interaction skills and reduction of parenting stress for children with high-functioning autism spectrum disorder (HFASD) and their parents in Japan. Twenty-two patients with HFASD from second to fourth grade and their parents were assigned to a training group (TG) or treatment as usual (TAU) and compared. The children with HFASD and their parents who were assigned to the TG participated in the manualized program for over a period of five to six months. Subjects provided demographic and medical information and completed teacher and parent-rating scales for social competence (Social Responsiveness Scale-2: SRS-2) and parent-rating of parenting stress (Parental Stress Index: PSI) and mental health (General Health Questionnaire-28: GHQ-28). The participants exhibited some improvements pre-, middle-, and post-treatment, particularly regarding the GHQ, PSI and SRS-2, as reported by parents. However, the social skills improvement reported by teachers was not significant. At the three-month follow-up, parent-rated GHQ and PSI maintained improvement, and SRS-2 achieved the greatest improvement from the baseline rating. Although some findings indicate that a program combination of SST and PT might be useful for enhancing social skills and improving parental stress and mental health, some subscales did not show a sufficient effect. Future research should consider program contents and provide longitudinal follow-up data to test the durability of the treatment.