A Causal and Mediation Analysis of the Comorbidity Between Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD)

Autism spectrum disorder (ASD) and Attention-deficit/hyperactivity disorder (ADHD) are often comorbid. The purpose of this study is to explore the relationships between ASD and ADHD symptoms by applying causal modeling. We used a large phenotypic data set of 417 children with ASD and/or ADHD, 562 affected and unaffected siblings, and 414 controls, to infer a structural equation model using a causal discovery algorithm. Three distinct pathways between ASD and ADHD were identified: (1) from impulsivity to difficulties with understanding social information, (2) from hyperactivity to stereotypic, repetitive behavior, (3) a pairwise pathway between inattention, difficulties with understanding social information, and verbal IQ. These findings may inform future studies on understanding the pathophysiological mechanisms behind the overlap between ASD and ADHD.     

Atypical Processing of Gaze Cues and Faces Explains Comorbidity between Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD)

This study investigated the neurobiological basis of comorbidity between autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). We compared children with ASD, ADHD or ADHD+ASD and typically developing controls (CTRL) on behavioural and electrophysiological correlates of gaze cue and face processing. We measured effects of ASD, ADHD and their interaction on the EDAN, an ERP marker of orienting visual attention towards a spatially cued location and the N170, a right-hemisphere lateralised ERP linked to face processing. We identified atypical gaze cue and face processing in children with ASD and ADHD+ASD compared with the ADHD and CTRL groups. The findings indicate a neurobiological basis for the presence of comorbid ASD symptoms in ADHD. Further research using larger samples is needed.     

Attention-deficit/Hyperactivity Disorder in the Context of Autism Spectrum Disorders

Autism spectrum disorders (ASD) are frequently marked by symptoms consistent with attention-deficit/hyperactivity disorder (ADHD), namely inattention, hyperactivity, and impulsivity. Recent work has established that about half of the ASD population also meets diagnostic criteria for ADHD, although the comorbid diagnoses are precluded by the DSM-IV-TR. Individuals with co-occurring ASD and ADHD symptoms are more severely impaired, with significant deficits seen in social processing, adaptive functioning, and executive control. Children with ASD and ADHD symptoms are also prone to motor problems, which lead to especially poor outcomes. Recent work has also demonstrated high rates of ASD symptoms in a subset of children with ADHD. Medication studies have demonstrated the efficacy of methylphenidate, atomoxetine, and guanfacine, among others, in treating ADHD symptoms co-occurring with ASD. However, these effects were not as great as those seen when treating primary ADHD, and they are less well-tolerated in the ASD population.     

Anxiety Symptoms in Boys with Autism Spectrum Disorder,Attention-Deficit Hyperactivity Disorder,or Chronic Multiple Tic Disorder and Community Controls

We compared symptoms of generalized anxiety disorder (GAD) and separation anxiety disorder (SAD) in 5 groups of boys with neurobehavioral syndromes: attention-deficit/hyperactivity disorder (ADHD) plus autism spectrum disorder (ASD), ADHD plus chronic multiple tic disorder (CMTD), ASD only, ADHD only, and community Controls. Anxiety symptoms were assessed using parent and teacher versions of a DSM-IV-referenced rating scale. All three groups of boys with co-morbid ADHD evidenced more severe anxiety than Controls. Group differences in anxiety varied as a function of symptom, disorder, informant, and co-morbidity supporting the notion that co-morbid neurobehavioral syndromes differentially impact clinical features of co-occurring anxiety symptoms. Findings also suggest that GAD and SAD are phenomenologically unique, even in children with ASD. Implications for nosology are discussed.     

Oppositional Defiant Disorder as a Clinical Phenotype in Children with Autism Spectrum Disorder

To examine the validity of oppositional defiant disorder (ODD) as a clinical phenotype distinct from attention-deficit hyperactivity disorder (ADHD), parents and teachers completed a DSM-IV-referenced rating scale and a background questionnaire for 608 children (ages 3-12 years) with autism spectrum disorder (ASD). The ASD sample was separated into four groups: ODD, ADHD, ODD + ADHD, and neither (NONE). Comparison samples were non-ASD clinic (n = 326) and community (n > 800) controls. In the ASD sample, all three ODD/ADHD groups were clearly differentiated from the NONE group, and the ODD + ADHD group had the most severe co-occurring symptoms, medication use, and environmental disadvantage. There were few differences between ASD + ODD and ASD + ADHD groups. Findings for ASD and control samples were similar, supporting overlapping mechanisms in the pathogenesis of ODD.     

Brief Report: Performance Pattern Differences Between Children with Autism Spectrum Disorders and Attention Deficit-Hyperactivity Disorder on Measures of Verbal Intelligence

Performance patterns on verbal subtests from the WISC-IV were compared between a clinically-referred sample of children with either autism spectrum disorders (ASD) or attention deficit/hyperactivity disorder (ADHD). Children with ASD demonstrated a statistically significant stepwise pattern where performance on Similarities was best, followed by Vocabulary, then Comprehension. Although children with ASD and ADHD share multiple behavioral features, this pattern was not observed for those with ADHD. Greater deficits in social reasoning and verbal formulation for children with ASD (compared to ADHD) are hypothesized to account for this observed difference in their performance pattern. Clinical implications, including use of this identified pattern in combination with other symptoms suggestive of ASD in referral decision making are discussed.     

Brief Report: Prevalence of Attention Deficit/Hyperactivity Disorder Among Individuals with an Autism Spectrum Disorder

Currently, both the DSM-IV-TR and ICD-10 preclude the diagnosis of Attention Deficit/Hyperactivity Disorder (ADHD) in cases that present with an Autism Spectrum Disorder (ASD). This criterion will be removed in the upcoming DSM-V, but the relationship between ASD and ADHD, and in particular the prevalence of ADHD among the ASD population, remains controversial. Previous studies have reported clinically significant ADHD symptoms in one-third to three-quarters of ASD-affected individuals (probands). In our sample of 1,838 simplex children and adolescents with ASD, we found that less than 16 % met clinically significant levels of ADHD symptoms, per parent report. When both parent and teacher reports were considered, the comorbidity rate was even lower, at 2 %.     

Buspirone Versus Methylphenidate in the Treatment of Attention Deficit Hyperactivity Disorder: A Double-Blind and Randomized Trial

The efficacy and side effects of buspirone compared with methylphenidate (MPH) in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). A total of 34 children with ADHD as defined by DSM-IV-TR were randomized to buspirone or methylphenidate dosed on weight-adjusted basis at buspirone (0.5 mg/kg/day) and methylphenidate (0.3–1 mg/kg/day) for a 6-week double-blind clinical trial. The principle measures of outcome were the teacher and parent ADHD Rating Scale. The side effects were assessed by the special side effect checklist of each drug. In both groups, the scores of teacher and parent ADHD Rating Scale significantly declined on the 6th week as compared to baseline (p = 0.001). These effects were observed in the subscales too. No significant differences were observed between the two protocols on the total scores of parent and teacher ADHD Rating Scale, but methylphenidate was superior to buspirone in decreasing the symptoms of inattention. The side effects of buspirone were mild and rare in comparison with MPH. Buspirone has a favorable side-effects profile. It also has clinically and statistically significant impacts on improving the ADHD symptoms in children. These preliminary findings of the efficacy of buspirone in children with ADHD need large and cross-over studies.     

Unexpected effects of methylphenidate in attention-deficit/hyperactivity disorder reflect decreases in core/secondary symptoms and physical complaints common to all children

Abstract Hypotheses concerning unexpected, psychostimulant-related effects reported in previous studies were examined by separating behavioral/physical complaints highly specific to methylphenidate (MPH) from those that (a) may mimic core/secondary symptoms of the disorder, or (b) are commonly reported by unmedicated children in the general population. Sixty-five children with attention-deficit/hyperactivity disorder (ADHD) participated in a double-blind, placebo-controlled, within-subject (crossover) experimental design and received a placebo and four MPH doses in counterbalanced order following baseline assessment. Behavioral and physical complaints were significantly higher under baseline relative to placebo and the four immediate-release MPH conditions (5 mg, 10 mg, 15 mg, and 20 mg) across three symptom categories: ADHD core/secondary symptoms; symptoms commonly reported in the general population, including unmedicated children with ADHD; and symptoms highly specific to MPH. No significant differences were found among active drug conditions. Past unexpected findings of psychostimulant effects in ADHD may be due to the inclusion of scale items that reflect core/secondary features of ADHD and normally occurring behavioral/physical complaints in children.     

Association of schizophrenia spectrum and autism spectrum disorder (ASD) symptoms in children with ASD and clinic controls

ObjectiveThis study examines relations between the severity of specific symptoms of schizophrenia spectrum disorder (SSD) and severity of the three defining symptom domains of autism spectrum disorder (ASD) in children with ASD (N = 147) and child psychiatry outpatient referrals (Controls; N = 339).MethodParticipants were subdivided into four groups depending on ASD status (±) and whether they met symptom criteria for attention-deficit/hyperactivity disorder (±ADHD). Their mothers and teachers evaluated them with a DSM-IV-referenced rating scale.ResultsCorrelations between schizoid personality symptoms and ASD social skills deficits were moderate to large, and this was true for children with ASD and Controls, regardless of ADHD status, and for mother's and teachers’ ratings. Conversely, severity of hallucinations, delusions, and disorganized thinking were minimally correlated with ASD severity with the exception of Controls with ADHD. The disorganized behavior and negative symptoms of schizophrenia evidenced the strongest pattern of associations with ASD symptoms, and this was particularly true for children with co-morbid ADHD (±ASD, all three ASD symptom dimensions), and for teachers’ ratings of all four groups. Nevertheless, there was considerable variability in relations for specific symptoms across informants and groups. Correlations between SSD symptom severity and IQ were generally low, particularly among the ASD Only group and for all teacher-rated symptoms.ConclusionAssociations between ASD and SSD symptoms were often dimension-specific, and this was particularly evident in children without ADHD (±ASD; mothers’ ratings). Findings were interpreted as supporting the deconstruction of complex clinical phenotypes as a means of better understanding interrelations among psychiatric syndromes.     

Event-Related Potential Study of Attention Regulation During Illusory Figure Categorization Task in ADHD,Autism Spectrum Disorder,and Typical Children

Autism spectrum disorders (ASD) and attention deficit/hyperactivity disorder (ADHD) are very common developmental disorder that share some similar symptoms of social, emotional, and attentional deficits. This study is aimed to help understand the differences and similarities of these deficits using analysis of dense-array event-related potentials (ERP) during an illusory figure recognition task. Although ADHD and ASD seem very distinct, they have been shown to share some similarities in their symptoms. Our hypothesis was that children with ASD will show less pronounced differences in ERP responses to target and nontarget stimuli as compared to typical children and, to a lesser extent, ADHD. Participants were children with ASD (N=16), ADHD (N=16), and controls (N=16). EEG was collected using a 128-channel EEG system. The task involved the recognition of a specific illusory shape, in this case a square or triangle, created by three or four inducer disks. There were no between-group differences in reaction time (RT) to target stimuli, but both ASD and ADHD committed more errors; specifically, the ASD group had statistically higher commission error rate than controls. Posterror RT in ASD group was exhibited in a posterror speeding rather than corrective RT slowing typical for the controls. The ASD group also demonstrated an attenuated error-related negativity as compared to ADHD and controls. The fronto-central P200, N200, and P300 were enhanced and less differentiated in response to target and nontarget figures in the ASD group. The same ERP components were marked by more prolonged latencies in the ADHD group as compared to both ASD and typical controls. The findings are interpreted according to the “minicolumnar” hypothesis proposing existence of neuropathological differences in ASD and ADHD, specifically minicolumnar number/width morphometry spectrum differences. In autism, a model of local hyperconnectivity and long-range hypoconnectivity explains many of the behavioral and cognitive deficits present in the condition, whereas the inverse arrangement of local hypoconnectivity and long-range hyperconnectivity in ADHD explains some deficits typical for this disorder. The current ERP study supports the proposed suggestion that some between-group differences could be manifested in the frontal ERP indices of executive functions during performance on an illusory figure categorization task.     

Brief Report: Associations Between Cognitive Control Processes and Traits of Autism Spectrum Disorder (ASD), attention-Deficit/Hyperactivity Disorder (ADHD) and Anxiety in Children at Elevated and Typical Familial Likelihood for ASD

Shared difficulties with cognitive control may play a role in co-occurring mental health problems frequently observed in autistic children. We investigated how different cognitive control processes (inhibitory control, conflict resolution, cognitive flexibility) associated with traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and anxiety in 7-year-old children at elevated (n = 44) and typical (n = 37) familial likelihood for ASD. Poor inhibitory control was associated with higher ADHD traits. Better inhibitory control and poorer cognitive flexibility predicted higher anxiety traits. Cognitive control processes were not associated dimensionally with autistic traits, though better conflict resolution predicted greater likelihood of meeting diagnostic criteria for ASD in categorical analysis. These findings suggest that different cognitive control alterations are associated with ASD, ADHD and anxiety.

     

Response to methylphenidate in children and adolescents with ADHD: does comorbid anxiety disorders matters?

There are controversial evidence in the literature on the role of comorbid anxiety disorders (ANX) in the improvement of attention-deficit/hyperactivity disorder (ADHD) symptoms with methylphenidate (MPH) treatment. Our main objective was to assess differences in the response to MPH treatment in children and adolescents with ADHD with and without comorbid ANX. We extensively evaluated response to MPH in a naturalistic study of 280 children and adolescent with ADHD according to DSM-IV criteria. Psychiatric diagnoses (ADHD, ANX, and other comorbidities) were assessed by semi-structured interviews (K-SADS-E). Response to MPH was assessed by means of total score in the Swanson, Nolan, and Pelham Scale-version IV (SNAP-IV) after 1 month of treatment. There was no significant between-group difference in the response to treatment with MPH after 1 month either when SNAP-IV scores were assessed dimensionally or categorically (moderate response) (P > 0.05). Our findings suggest that comorbid ANX do not interfere in the response to MPH on core ADHD symptoms.     

A preliminary study on the effect of methylphenidate on motor performance in children with comorbid DCD and ADHD

Attention Deficit Hyperactive Disorder (ADHD) and Developmental Coordination Disorder (DCD) are two developmental disorders with considerable comorbidity. The impact of Methylphenidate (MPH) on ADHD symptoms is well documented. However, the effects of MPH on motor coordination are less studied. We assessed the influence of MPH on motor performance of children with comorbid DCD and ADHD. Participants were 18 children (13 boys, mean age 8.3 years) diagnosed with comorbid DCD and ADHD. A structured clinical interview (K-SADS-PL) was used to determine psychopathology and the Movement Assessment Battery for Children–Checklist were used to determine criterion for motor deficits. The Movement Assessment Battery for Children (M-ABC) was administrated to all participants once under the influence of MPH and once under a placebo pill condition. The motor tests were administered on two separate days in a double-blinded design. Participants’ motor performance with MPH was significantly superior to their performance in the placebo condition. Significant improvement was observed in all the M-ABC sub-tasks except for static balance performance. The findings suggest that MPH improves motor coordination in children with comorbid DCD and ADHD but clinically significant improvement was found in only 33% of the children.     

Adverse response to methylphenidate in combination with valproic acid

The use of methylphenidate (MPH) in combination with antiepileptic drugs is gaining acceptance for children with epilepsy who have the symptoms of attention-deficit hyperactivity disorder (ADHD). We report two cases of an adverse effect of dyskinesia and bruxism when MPH was given to children maintained on valproic acid. These adverse effects were rapid and severe. Because of the potential for serious and persistent side effects from this combination of medications, caution is warranted in the treatment of ADHD with MPH for children taking valproic acid. Further prospective studies of the use of valproic acid and MPH in combination are required.     

Response Inhibition in Adults with Autism Spectrum Disorder Compared to Attention Deficit/Hyperactivity Disorder

Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are hypothesised to involve core deficits in executive function. Previous studies have found evidence of a double dissociation between the disorders on specific executive functions (planning and response inhibition). To date most research has been conducted with children. No studies have directly compared the stable cognitive profile of adults. It was hypothesised that adults with ASD would show generally intact response inhibition whereas those with ADHD would show more global impairment. Participants were 24 adults aged 18–55 with high functioning ASD, 24 with ADHD, and 14 age and IQ matched controls. Participants completed three standardised measures of response inhibition. Participants with ASD had generally intact response inhibition but slow response latencies, possibly due to deficits in response initiation. Adults with ADHD did not show the more global impairments hypothesised. There were some significant differences between the clinical groups across measures of inhibition. In terms of performance style, adults with ASD were slow and accurate whilst those with ADHD showed an impulsive style.     

Error and feedback processing in children with ADHD and children with Autistic Spectrum Disorder: an EEG event-related potential study

OBJECTIVE: Performance monitoring was investigated in typically developing (TD) children, children with Autistic Spectrum Disorder (ASD), and Methylphenidate (Mph)-treated and medication-free children with Attention Deficit Hyperactivity Disorder (ADHD). METHODS: Subjects performed a feedback-based learning task. Event-related Potentials (ERPs) time locked to responses and feedback were derived from the EEG. RESULTS: Compared to the TD and ASD groups, the medication-free ADHD group showed a decreased response-locked Error Related Negativity (ERN) and error Positivity (Pe), particularly as learning progressed throughout the task. Compared to the medication-free ADHD group, the Methylphenidate-treated group showed a normalised Pe. All clinical groups showed or tended to show a decreased feedback-locked late positive potential to negative feedback. CONCLUSIONS: The ERPs suggest that medication-free children with ADHD, but not with ASD, have a diminished capacity to monitor their error responses when they are learning by performance feedback. This capacity partially 'normalises' in Mph-treated children with ADHD. Both children with ADHD and children with ASD are suggested being compromised in affective feedback processing. SIGNIFICANCE: This study shows that measuring ERPs of error and feedback processing is a useful method for (1) dissociating ADHD from ASD and (2) elucidating medication effects in ADHD on component processes of performance monitoring.     

Are parental autism spectrum disorder and/or attention-deficit/Hyperactivity disorder symptoms related to parenting styles in families with ASD (+ADHD) affected children?

An understudied and sensitive topic nowadays is that even subthreshold symptoms of autism spectrum disorder (ASD) and attention-deficit/Hyperactivity disorder (ADHD) in parents may relate to their parenting styles. The aim of this study was to explore the influence of (the combined) effect of child diagnosis (ASD or ASD + ADHD affected/unaffected children) and parental ASD and/or ADHD on parenting styles. Ninety-six families were recruited with one child with a clinical ASD (+ADHD) diagnosis, and one unaffected sibling. Parental ASD and ADHD symptoms were assessed using self-report. The Parenting Styles Dimensions Questionnaire (PSDQ) self- and spouse-report were used to measure the authoritative, authoritarian, and permissive parenting styles. Fathers and mothers scored significantly higher than the norm data of the PSDQ on the permissive style regarding affected children, and lower on the authoritative and authoritarian parenting style for affected and unaffected children. Self- and spouse-report correlated modestly too strongly. Higher levels of paternal (not maternal) ADHD symptoms were suboptimally related to the three parenting styles. Further, two parent–child pathology interaction effects were found, indicating that fathers with high ADHD symptoms and mothers with high ASD symptoms reported to use a more permissive parenting style only towards their unaffected child. The results highlight the negative effects of paternal ADHD symptoms on parenting styles within families with ASD (+ADHD) affected offspring and the higher permissiveness towards unaffected offspring specifically when paternal ADHD and/or maternal ASD symptoms are high. Parenting training in these families may be beneficial for the well-being of all family members.     

Treatment for Co-Occurring Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

Interest in the co-occurrence of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) has grown in the last decade. Research on clinical populations supports the frequent co-occurrence of ADHD traits (e.g., hyperactivity) in individuals with ASD and ASD traits (e.g., social communication deficits) in individuals with ADHD. Similar trends in co-occurring traits have been observed in population-based samples, as well as family and genetic studies of affected individuals. Despite increased interest in co-occurring ADHD and ASD, relatively little research has been devoted to treatment considerations. The vast majority of intervention research has examined pharmacological treatment using traditional ADHD medications. Relatively few psychosocial interventions have directly addressed co-occurring symptoms. Treatment development will benefit from enhanced understanding of the phenomenon of co-occurring ADHD and ASD. Key topics for future research include examining developmental trajectories of co-occurring disorders, comorbid psychiatric conditions, deficits in social skills, and the nature of executive functioning impairment in individuals with co-occurring ADHD and ASD. In the current review, research in these areas is reviewed along with recommendation for future study. Given that clinicians are routinely observing and treating individuals with co-occurring symptoms, further research will yield needed information to inform intervention development and maximize benefits for affected individuals.     

Use of Stimulants in Bipolar Disorder

Several international guidelines indicate stimulants, including methylphenidate (MPH), amphetamines and derivatives, modafinil, and armodafinil among the second-third-line choices for bipolar depression. Efficacy of stimulants has been also reported for the management of residual depressive symptoms such as fatigue and sleepiness and for the management of affective, cognitive, and behavioral symptoms in children and adult bipolar patients with comorbid ADHD. Few case reports show positive results with MPH in the treatment of resistant mania. Finally, MPH might be an option in some bipolar forms observed in psychiatric presentations of frontotemporal dementia and traumatic brain injury. In spite of these preliminary observations, the use of stimulants in bipolar patients is still controversial. Potential of misuse and abuse and mood destabilization with induction of (hypo)manic switches, mixed states, and rapid cycling are the concerns most frequently reported. Our aims are to summarize available literature on this topic and discuss practical management implications.