Treating children with attention-deficit/hyperactivity disorder and comorbid epilepsy

Attention-deficit/hyperactivity disorder (ADHD) is one of common neurodevelopmental disorder often comorbid with epilepsy. There are no existing guidelines on how to manage these two conditions when they are comorbid. To identify relationship between epilepsy and ADHD and to know role of antiepileptics and safety of stimulant like methylphenidate in such conditions from existing literature, we searched articles published in clinical journals available online between 1990-2010, with these key words in medline:children, epilepsy, seizure, comorbid, ADHD, treatment. Relevant abstracts were further selected for their focus on current topic. Cross references were extracted. Finally relevant articles that included original research articles, reviews and abstracts of non-english literature were used. Children with epilepsy may manifest with symptoms of ADHD. Children with ADHD may develop epilepsy. Some antiepileptics like phenobarbitone, gabapentin, topiramate may not be helpful in controlling behavioral symptoms of ADHD. Stimulants are the main stay of pharmacotherapy for ADHD but there is risk of decreasing seizure threshold in children with comorbid epilepsy especially when their epilepsy is not well controlled. Existing evidence is not in favor of screening children with ADHD for EEG abnormality before starting stimulant therapy.     

Gyrification differences in children and adolescents with velocardiofacial syndrome and attention-deficit/hyperactivity disorder: A pilot study

We used magnetic resonance imaging to investigate brain gyrification patterns between 19 children with attention-deficit/hyperactivity disorder (ADHD), 9 children with velocardiofacial syndrome (VCFS), and 23 control children. We found that VCFS is associated with widespread decreases in gyrification. In ADHD, we found minor differences from control children. No evidence was found for common gyrification patterns between VCFS and ADHD children.     

A longitudinal study of neuropsychological functioning and academic achievement in children with and without signs of attention-deficit/hyperactivity disorder

Objective: Attention-deficit/hyperactivity disorder (ADHD) in childhood is associated with poor academic functioning. Deficits in academic functioning have proven to be less responsive to intervention than behavioral deficits in this population, yet the causes of this academic underperformance are not well understood. The purpose of this study is to examine the relationship between ADHD and academic performance in elementary-aged children in a developmental context. To do this, we study important cognitive variables and academic achievement over a three-year timeframe. Method: Based on teacher ratings of ADHD, children were divided into a high symptom group (n = 17) and a low symptom group (n = 34). A thorough battery of cognitive and academic tests was administered at Time 1 and again 2 years later. Cognitive measures focused specifically on working memory and response inhibition. Results: Results indicate that children who have high levels of ADHD signs differ from their low-sign peers in academic achievement and in several cognitive domains. Differences in cognitive functioning show a developmental trend consistent with earlier developmental delays in response inhibition and later delays in working memory. Working memory appears to be particularly important in several academic domains. Importantly, in a longitudinal model, working memory was more predictive of math achievement for students demonstrating signs of ADHD than for those who did not. Conclusion: The relationship between these cognitive variables and academic functioning are explicated in the domains of reading, math, and problem solving.     

Hyperactivity in boys with attention-deficit/hyperactivity disorder (ADHD): The role of executive and non-executive functions

Motor activity of boys (age 8–12 years) with (n = 19) and without (n = 18) ADHD was objectively measured with actigraphy across experimental conditions that varied with regard to demands on executive functions. Activity exhibited during two n-back (1-back, 2-back) working memory tasks was compared to activity during a choice-reaction time (CRT) task that placed relatively fewer demands on executive processes and during a simple reaction time (SRT) task that required mostly automatic processing with minimal executive demands. Results indicated that children in the ADHD group exhibited greater activity compared to children in the non-ADHD group. Further, both groups exhibited the greatest activity during conditions with high working memory demands, followed by the reaction time and control task conditions, respectively. The findings indicate that large-magnitude increases in motor activity are predominantly associated with increased demands on working memory, though demands on non-executive processes are sufficient to elicit small to moderate increases in motor activity as well.     

A novel unstructured performance-based task of executive function in children with attention-deficit/hyperactivity disorder

Objective: Executive functions (EFs) have been assessed with performance-based measures and rating scales. Research has shown a lack of association between these two methods. One factor that might contribute to this difference is the structure provided on performance-based measures that is not provided on rating scales. This study examined the role of structure on self-directed task completion, an aspect of EF, using a novel unstructured performance-based task (UPT).

Method: Children aged 8–12 years (38 attention-deficit/hyperactivity disorder, ADHD; 42 typically developing) and their caregivers participated. We compared performance on the UPT, performance-based measures of EF (Stroop test and Trail-Making Test), and a rating scale to assess EF (Barkley Deficits in Executive Functioning Scale–Children and Adolescents, BDEFS–CA).

Results: Group differences were found across all measures. Significant associations emerged between the UPT and Stroop test, Trail-Making Test, and BDEFS–CA, but no significant associations were found between the Stroop test or Trail-Making Test and the BDEFS–CA. In regression analyses, performance-based tasks and the rating scale both uniquely predicted UPT performance. The UPT was a significant predictor of group status when entered with performance-based tasks, but the UPT did not enter as a significant predictor when entered with the rating scale.

Conclusion: The UPT is a promising measure to assess self-directed task completion in children with ADHD.     

Attention lapses in children with spina bifida and hydrocephalus and children with attention-deficit/hyperactivity disorder

Attentional lapses are usually defined as temporary and often brief shifts of attention away from some primary task to unrelated internal information processing. This study addressed the incidence of attention lapses and differences in attentional functioning in 30 children with attention-deficit/hyperactivity disorder (ADHD), 26 healthy children, and 29 children with spina bifida myelomeningocele and hydrocephalus (SBH). Assessments were conducted using computerized tonic and phasic attention tests, the Symbol Digit Modalities Test (SDMT), and the Trail Making Test Form B (TMT–B). The group with SBH differed from normal controls on cognitive measures of attention and executive functions. The ADHD group obtained lower scores than the SBH group and healthy children. ANOVA results showed that there was an effect of shunt revisions and shunt-related infections on neuropsychological performance. Lapses of attention together with reaction time may thus represent important factors for the understanding of cognitive deficits in SBH.     

Cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder

A growing body of literature has examined the cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). However, a clear understanding of the types and magnitude of such effects are difficult to discern from such a large and varied collection of published reports. This review evaluated a total of 40 relevant placebo-controlled studies published since Rapport and Kelly's [1993. Psychostimulant effects on learning and cognitive function. In: Matson, J.L. (Ed.), Handbook of Hyperactivity in Children. Allyn & Bacon, Boston, pp. 97–136] original review of cognitive effects of methylphenidate in children with ADHD. Of these published studies, 63.5% identified some improvement in cognitive function following methylphenidate treatment. Methylphenidate improved performance on saccadic eye movement, planning/cognitive flexibility, attention/vigilance, and inhibitory control tasks in 83.3%, 71.4%, 70.6%, and 69.7% of studies, respectively. A total 58.3% and 50% of studies that evaluated the effect of methylphenidate on tasks of memory and working memory/divided attention, respectively, noted improvement. Variability of findings across studies may be explained by differential effects of methylphenidate on brain function, intra- and inter-individual variability in medication response, methodological limitations, and problems associated with repeated neuropsychological assessment and metric properties of commonly utilised neuropsychological instruments.     

Parent-reported problematic sleep behaviors in children with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder

BackgroundSleep problems are frequent and well documented in children with Autism Spectrum Disorders (ASD), children with Attention Deficit/Hyperactivity Disorder (ADHD) and children with internalizing problems, however limited work has examined sleep problems in children presenting with comorbid ASD/ADHD. In healthy children, sleep problems negatively impact social, emotional, and academic functioning. The current study sought to examine diagnostic severity as predictors of sleep problems in children with comorbid ASD/ADHD. Additionally, the association between sleep and “real-life” functional domains (i.e., intellectual functioning, academic achievement, and executive functioning) were assessed.MethodSleep, internalizing difficulties, intellectual functioning, academic achievement and executive functioning were assessed in 85 children with who carried the dual diagnoses of ASD and ADHD.ResultsInternalizing difficulties, rather than ASD or ADHD symptom severity, was the most consistent predictor of problematic sleep behaviors (i.e., nightmares overtiredness, sleeping less than other children, trouble sleeping, and Total Problematic Sleep Behaviors) in this sample. Further, parent report of problematic sleep behaviors was significantly associated with functional domains after controlling for ASD, ADHD, and internalizing symptoms.ConclusionsResults suggest that internalizing symptoms are associated with problematic sleep behaviors in children with comorbid ASD/ADHD and may have implications for the “real-life” functioning among children with comorbid ASD/ADHD.     

Examining the relationship between obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in children and adolescents: a familial risk analysis.

BACKGROUND: To use family study methodology to examine the relationship between obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. METHODS: We assessed for ADHD and OCD in the 1533 first-degree relatives of three groups of index children: those with ADHD and OCD, those with ADHD but no OCD, and matched controls with neither disorder. RESULTS: The risk for ADHD was similarly elevated in families of ADHD youth with (18.9%) and without OCD (20.1%; p = .91), and both groups had significantly higher rates of ADHD compared with controls (4.6%; p < or = .001), which was consistent with previous research showing a strong familial risk for ADHD. The risk for OCD was significantly elevated only among relatives of youth with ADHD plus comorbid OCD (13.0%) compared with controls (.5%; p < or = .001) and was consistent with previous research showing a strong familial risk for OCD. Relatives affected with ADHD had a significantly elevated risk for OCD compared with relatives unaffected by ADHD (7.4% vs. 1.3%; p < .001), suggestive of co-segregation between these disorders. There was no evidence of nonrandom mating between ADHD- and OCD-affected spouses. CONCLUSIONS: These results extend previously reported findings regarding the heritability of both ADHD and OCD and provide new evidence of a familial relationship between ADHD and pediatric OCD that best fits the hypothesis of a unique familial subtype.     

Inattention symptoms and the diagnosis of comorbid attention-deficit/hyperactivity disorder among youth with generalized anxiety disorder

Generalized anxiety disorder (GAD) and attention-deficit/hyperactivity disorder (ADHD) commonly co-occur in childhood. Inattention symptoms can be hallmarks of both conditions, however assessment tools of inattention may not effectively distinguish between the two conditions. The present study used receiver operating characteristic (ROC) analyses to examine the high-end specificity of the Attention Problems Scale of the Child Behavior Checklist (CBCL) for detecting comorbid ADHD among youth with GAD (N = 46). Results support the utility of the Attention Problems Scale for accurately distinguishing between the two groups (AUC = .84, SE = .06). Specifically, a cut score of 63 achieved the most favorable values across diagnostic utility indices; 74% of GAD youth with ADHD scored above this cutoff and 91% of GAD youth without ADHD scored below this cutoff. Findings provide support for the use of the CBCL Attention Problems Scale to supplement diagnostic interviews and identify inattention associated with ADHD among GAD youth.     

Factors related to diagnostic persistence of attention deficit/hyperactivity disorder in Turkish children and adolescents

Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most frequently occurring mental disorders in children and adolescents. The purpose of this study was to determine diagnostic persistence three years after the first clinical evaluation and to investigate the factors relating to diagnostic persistence in children and adolescents with ADHD. Methods: The study included 183 children and adolescents who were evaluated in the first admission. Of 183 children and adolescents, 142 children and adolescents were evaluated in the second admission and only the data of 142 children and adolescents were analysed in the study. Diagnostic persistence was defined as having met the full criteria for ADHD on second evaluation. Symptom severity of ADHD was determined using the Turgay DSM-IV-based Child and Adolescent Behavior Disorders Screening and Rating Scale-Parents Form (T-DSM-IV-S). Intelligence level was assessed through the Wechsler Intelligence Scale for Children-Revised. Results: Of the children included in the study, 77.5% (n?=?110) were determined to have ADHD diagnostic persistence. Low intelligence levels, younger age and higher T-DSM-IV-S inattention and conduct disorder scores were associated with diagnostic persistence. ADHD diagnosis in children and adolescents tends to continue at high rates. Conclusions: Determination of the risks related to ADHD diagnostic persistence may contribute to improved treatment planning and interventions.     

Effect of trait anxiety on cognitive test performance in adolescents with and without attention-deficit/hyperactivity disorder

Introduction: Attention-deficit/hyperactivity disorder (ADHD) and anxiety are frequently comorbid disorders associated with different types of abnormal performance on neuropsychological tests. Although some studies have shown that comorbid anxiety alters ADHD test performance, results inconsistently show both improvements and worsening of different abilities, with failures to replicate across different anxiety disorders. Alternatively, trait anxiety may reflect a more stable influence on ADHD test performance than various diagnosable anxiety disorders. Method: To better understand the possible enhancing or deleterious effects of anxiety on ADHD cognitive impairments, this study examined the effect of individual differences in trait anxiety measured by the Multidimensional Anxiety Scale for Children (MASC) on a battery of computerized, rapid-performance tests measuring attention and impulsivity-related performance in 98 Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition (DSM–IV) Combined-Subtype ADHD adolescents and 123 healthy controls. It was hypothesized that trait anxiety would attenuate response inhibition and attention deficits in ADHD. Results: ADHD-diagnosed adolescents with higher trait anxiety performed better on indices of sustained attention, reaction time, and motor variability, and had altered overall test-performance strategy, while response inhibition was affected in both ADHD and non-ADHD. Conclusions: This study provides the first evidence that pathological levels of anxiety are not needed to see differences in ADHD neuropsychological test performance. Instead, mildly elevated trait anxiety confers a protective influence by reducing the degree of impairment seen in ADHD. These findings suggest that better performing ADHD adolescents might have optimized levels of cortical arousal, and raise new questions about how best to identify the neurobiological substrates responsible for the beneficial effects.     

Prevalence of attention-deficit/hyperactivity disorder in individuals with autism spectrum disorder: A meta-analysis

BackgroundComorbidity with attention-deficit/hyperactivity disorder (ADHD) is very common in autism spectrum disorder (ASD), worsening the developmental trajectory of ASD. The reported rates of ADHD in ASD vary widely. However, no meta-analysis has been conducted specifically to assess both the current and lifetime prevalence of ADHD in ASD. This study aims to fill in this gap.MethodWe searched the Web of Science, PubMed, PsycINFO, CINAHL, and Embase databases for eligible articles published between January 1, 2000, and September 5, 2020. The risk of bias tool was used to assess the studies’ quality. Overall pooled estimates of the current and lifetime prevalence of ADHD in ASD were obtained using random-effects models. Study heterogeneity was examined by Q and I² statistics.FindingsA total of 63 articles were eventually included, of which 56 studies reported the current prevalence, and 13 studies reported the lifetime prevalence. The results revealed that the pooled current and lifetime prevalence rates of ADHD among ASD were 38.5 % (95 % CI 34.0–43.2) and 40.2 % (95 % CI 34.9–45.7), respectively. Our study also confirmed that age, intellectual disability, recruitment settings, and diagnostic criteria significantly influenced the current prevalence of ADHD in ASD.ConclusionASD has considerable high current or lifetime prevalence rates of co-occurring ADHD. The findings demonstrate that clinicians should consider the high prevalence of ADHD in ASD and especially stay alert to possible ADHD diagnoses in school-age children and adolescents with ASD. Medical institutions should improve the assessment and tracking system of ADHD comorbidity in ASD and maximize the diagnostic accuracy for better treatment.     

Common and specific genes and peripheral biomarkers in children and adults with attention-deficit/hyperactivity disorder

Objectives: Elucidating the biological mechanisms involved in attention-deficit/hyperactivity disorder (ADHD) has been challenging. Relatively unexplored is the fact that these mechanisms can differ with age.

Methods: We present an overview on the major differences between children and adults with ADHD, describing several studies from genomics to metabolomics performed in ADHD children and in adults (cADHD and aADHD, respectively). A systematic search (up until February 2016) was conducted.

Results: From a PRISMA flow-chart, a total of 350 and 91 genomics and metabolomics studies were found to be elligible for cADHD and aADHD, respectively. For children, associations were found for genes belonging to dopaminergic (SLC6A3, DRD4 and MAOA) and neurodevelopmental (LPHN3 and DIRAS2) systems and OPRM1 (Yates corrected P?=?0.016; OR?=?2.27 95%CI: 1.15–4.47). Studies of adults have implicated circadian rhythms genes, HTR2A, MAOB and a more generic neurodevelopmental/neurite outgrowth network (BCHE, SNAP25, BAIAP2, NOS1/NO, KCNIP4 and SPOCK3; Yates corrected P?=?0.007; OR?=?3.30 95%CI: 1.33–8.29). In common among cADHD and aADHD, the most significant findings are for oxidative stress proteins (MAD, SOD, PON1, ARES, TOS, TAS and OSI), and, in the second level, DISC1, DBH, DDC, microRNA and adiponectin.

Conclusions: Through a convergent functional genomics, this review contributes to clarification of which genetic/biological mechanisms differ with age. The effects of some genes do not change throughout the lifetime, whereas others are linked to age-specific stages. Additional research and further studies are needed to generate firmer conclusions that might someday be useful for predicting the remission and persistence of the disorder. Despite the limitations, some of these genes/proteins could be potential useful biomarkers to discriminate cADHD from aADHD.     

Executive function in children with pervasive developmental disorder and attention-deficit/hyperactivity disorder assessed by the Keio version of the Wisconsin card sorting test

The Wisconsin card sorting test (WCST) comprehensively examines executive function (EF). The Keio version of the WCST (KWCST) uses fewer cards and presents them in two steps, separated by a short pause during which an instruction is given. Being of short duration, this test is suitable for children with pervasive developmental disorder (PDD) and attention-deficit/hyperactivity disorder (AD/HD), yet few studies have examined the performance of children with such developmental disorders in the second step of a two-step test such as the KWCST. Using the KWCST, this study compares EF in children with PDD (n=52), or AD/HD (n=46) to that in typically developing (TD) children (n=52). Scores for the six indices of this test, including numbers of response cards until the first category achieved (NUCA), total errors (TE), and non-perseverative errors of Nelson (NPEN), were analyzed using ANOVA. Compared to the TD group, scores in the PDD and/or AD/HD groups were significantly lower for all indices except NUCA and NPEN for the first step, and lower for all indices except NUCA for the second step. Moreover, significantly fewer improvements in TE were seen in the PDD group, and significantly fewer improvements in NPEN were seen in the AD/HD group, compared with TD. This study suggests that both PDD and AD/HD make it difficult for children to utilize their experience in the first step and to effectively apply the instruction given before the second step. It also suggests that the two-step nature of the KWCST is clinically important.     

Neurobehavioral and hemodynamic evaluation of Stroop and reverse Stroop interference in children with attention-deficit/hyperactivity disorder

Failure of executive function (EF) is a core symptom of attention-deficit/hyperactivity disorder (ADHD). However, various results have been reported and sufficient evidence is lacking. In the present study, we evaluated the characteristics of children with ADHD using the Stroop task (ST) and reverse Stroop task (RST) that reflects the inhibition function of EF. We compared children with ADHD, typically developing children (TDC), and children with autism spectrum disorder (ASD), which is more difficult to discriminate from ADHD. A total of 10 children diagnosed with ADHD, 15 TDC, and 11 children diagnosed with ASD, all matched by age, sex, language ability, and intelligence quotient, participated in this study. While each subject performed computer-based ST and RST with a touch panel, changes in oxygenated hemoglobin (oxy-Hb) were measured in the prefrontal cortex (PFC) by near-infrared spectroscopy (NIRS) to correlate test performance with neural activity. Behavioral performance significantly differed among 3 groups during RST but not during ST. The ADHD group showed greater color interference than the TDC group. In addition, there was a negative correlation between right lateral PFC (LPFC) activity and the severity of attention deficit. Children with ADHD exhibit several problems associated with inhibition of color, and this symptom is affected by low activities of the right LPFC. In addition, it is suggested that low hemodynamic activities in this area are correlated with ADHD.     

Linear and non-linear EEG analysis of adolescents with attention-deficit/hyperactivity disorder during a cognitive task

Objective

We aimed to investigate whether electroencephalograph (EEG) dynamics differ in adolescents with attention-deficit/hyperactivity disorder (ADHD) compared with healthy subjects during the performance of a cognitive task.

Methods

We recorded EEGs from 19 scalp electrodes in 11 adolescent boys with ADHD and 12 age-matched healthy boys while the subjects were at rest and during a continuous performance test (CPT). The approximate entropy (ApEn), a non-linear information-theoretic measure, was calculated to quantify the complexity of the EEGs.

Results

The mean ApEn of the ADHD patients was significantly lower than the healthy subjects over the right frontal regions (Fp2 and F8) during the performance of the cognitive task, but not at rest. The spectral analysis showed significant differences between the two groups in the P3 and T4 regions at rest and the Fp2 and F8 regions during task performance.

Conclusions

The differences in EEG complexity between the two groups suggest that cortical information processing is altered in ADHD adolescents, and thus their levels of cortical activation may be insufficient to meet the cognitive requirements of attention-demanding tasks.

Significance

This study suggests that a non-linear measure such as ApEn is useful for investigating neural dysfunctions in adolescents with ADHD.     

Attentional functions in children and adolescents with attention-deficit/hyperactivity disorder with and without comorbid tic disorder

Summary Although the coexistence of attention-deficit/hyperactivity disorder (ADHD) and tic disorder (TD) is common, the nature of association is yet not fully understood. Thus, the aim of the present study was to explore attentional dysfunction in children with pure ADHD compared to children with comorbid ADHD + TD. Three groups of 20 children each, aged 8–15 years with either ADHD, ADHD + chronic tic disorder or Tourette syndrome (ADHD + TD) and a healthy control group were compared in their performance on three computerized attention tasks. Tasks of sustained attention, selective attention and interference control were employed. In addition, parental ratings of ADHD symptom severity and behaviour problems were obtained. Both clinical groups were rated as equally inattentive, however, externalising symptoms were more severe in the ADHD group. Objective measures of attentional performance revealed differences between the groups: whereas the ADHD group was markedly impaired in sustaining attention and selective attention/inhibitory control, the ADHD + TD group only showed marginal deficits in selective attention/inhibitory control. Possible explanations for the superior performance of the comorbid group are discussed: In particular, the results may indicate that in some patients, the tic disorder produces behavioural symptoms of ADHD, but not the broad neurocognitive deficits that usually are associated with ADHD. Alternatively, compensatory neural mechanisms of TD patients may result in a better neuropsychological performance of comorbid patients relative to patients suffering from pure ADHD. Correspondence: Ellen Greimel, Child Neuropsychology Section, Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Aachen, 52074 Aachen, Germany     

Motor skills in Czech children with attention-deficit/hyperactivity disorder and their neurotypical counterparts

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioural disorder. Characterized by recurring problems with impulsiveness and inattention in combination with hyperactivity, motor impairments have also been well documented in the literature. The aim of this study was to compare the fine and gross motor skills of male and female children with ADHD and their neurotypical counterparts within seven skill assessments. This included three fine motor tasks: (1) spiral tracing, (2) dot filling, (3) tweezers and beads; and four gross motor tasks: (1) twistbox, (2) foot tapping, (3) small plate finger tapping, and (4) large plate finger tapping. It was hypothesized that children with ADHD would display poorer motor skills in comparison to neurotypical controls in both fine and gross motor assessments. However, statistically significant differences between the groups only emerged in four of the seven tasks (spiral tracing, dot filling, tweezers and beads and foot tapping). In line with previous findings, the complexity underlying upper limb tasks solidified the divide in performance between children with ADHD and their neurotypical counterparts. In light of similar research, impairments in lower limb motor skill were also observed. Future research is required to further delineate trends in motor difficulties in ADHD, while further investigating the underlying mechanisms of impairment.