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.     

Diagnosis and treatment of attention-deficit/hyperactivity disorder

TOPIC: Diagnosis and treatment of attention deficit/hyperactivity disorder. PURPOSE: To describe a multidimensional approach to treatment of children with attention deficit/hyperactivity and their parents. SOURCES: Review of the literature and of the author's clinical work. CONCLUSIONS: A great deal of controversy surrounds this diagnosis. The nurse psychotherapist helps children and families through the diagnostic process and into the treatment phase. Emphasis is on psychotherapy of the child and family, parent education, and attention to the child's school environment and social adjustment.     

Structural brain imaging of attention-deficit/hyperactivity disorder.

Many investigators have hypothesized that attention-deficit/hyperactivity disorder (ADHD) involves structural and functional brain abnormalities in frontal-striatal circuitry. Although our review suggests that there is substantial support for this hypothesis, a growing literature demonstrates widespread abnormalities affecting other cortical regions and the cerebellum. Because there is only one report studying adults with ADHD, this summary is based on children. A key limitation of the literature is that most of the studies until recently have been underpowered, using samples of fewer than 20 subjects per group. Nevertheless, these studies are largely consistent with the most comprehensive and definitive study (Castellanos et al 2002). Moreover, studies differ in the degree to which they address the influence of medications, comorbidities, or gender, and most have not addressed potentially important sources of heterogeneity such as family history of ADHD, subtype, or perinatal complications. Despite these limitations, a relatively consistent picture has emerged. The most replicated alterations in ADHD in childhood include significantly smaller volumes in the dorsolateral prefrontal cortex, caudate, pallidum, corpus callosum, and cerebellum. These results suggest that the brain is altered in a more widespread manner than has been previously hypothesized. Developmental studies are needed to address the evolution of this brain disorder into adulthood.     

Characteristics of adults with attention-deficit/hyperactivity disorder and past conduct disorder

Objective: DSM‐IV Attention‐deficit/hyperactivity disorder (ADHD) comorbid with DSM‐IV conduct disorder (CD) in childhood/adolescence has been proposed as a ‘distinct subtype’. The present study investigated subsequent psychopathological characteristics of this proposed subtype in adults. Method: Questionnaires were completed by 71 adults (mean age 29.6 years) with ADHD and their informants. Results: The 39 subjects with a history of past CD, when compared with the remaining subjects, were associated with significantly increased ratings of aspects of ADHD‐related impulsivity, with features of all three DSM‐IV ‘Clusters’ of personality disorders (PDs) (in particular of ‘Cluster B’ PDs) and with other psychopathology. Also, there were significant correlations between the number of endorsed past CD criteria and various self‐ratings of psychopathology. Conclusion: The results indicate the psychopathological characteristics of adults with a history of the proposed ‘ADHD with CD’ subtype. The findings are relevant to future studies of ADHD subtypes in adults.     

Neuropsychological assessment of attention in adults with different subtypes of attention-deficit/hyperactivity disorder

Summary There is only little information about varying attention functions of adults with different DSM-IV subtypes of attention-deficit/hyperactivity disorder (ADHD). In the present study groups of adult patients with ADHD – predominantly inattentive type, ADHD – predominantly hyperactive-impulsive type or ADHD – combined type and three healthy control groups were compared regarding multiple components of attention. Assessment of attention was performed using a computerized neuropsychological test battery for attentional functions. In comparison with healthy subjects, the three patient groups displayed impairments of vigilance, selective attention, divided attention, and flexibility. These impairments of attention of ADHD subgroups were primarily observed with regard to reaction time. With regard to tonic and phasic alertness no differences between patient and control groups could be found. Comparison between ADHD subgroups revealed that DSM-IV subtypes of ADHD differ in measures of divided attention, selective attention and flexibility. Differences between ADHD subgroups were primarily observed with regard to task accuracy. The results suggest that while distinct profiles of attentional functioning were observed between adult patients with ADHD and healthy adults indicating gross disturbances of various attention functions in patients with ADHD, differences between ADHD subgroups were only weak. Correspondence: Oliver Tucha, School of Psychology, University of Plymouth, Drake Circus, Plymouth, Devon PL4 8AA, UK     

The potential role of clock genes in children attention-deficit/hyperactivity disorder

BackgroundAttention deficit/ hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder and is thought to be associated with circadian system.MethodsWe performed a pathway-based study to test individual single nucleotide polymorphisms (SNPs) and the overall evidence of genetic polymorphisms involved in the circadian pathway in association with children ADHD susceptibility among a Chinese population. A community-based case–control study was conducted among Chinese children, and 168 ADHD patients and 233 controls were recruited using a combination diagnosis based on the diagnostic and statistical manual of mental disorders iv (DSM-IV) ADHD rating scale, Swanson, Nolan, and Pelham rating scale (SNAP-IV) rating scale, and semi-structured clinical interview.ResultsThe results of single-loci analyses identified that PER1 rs2518023 and ARNTL2 rs2306074 were nominally association with ADHD susceptibility (P < 0.05). Next, we applied multifactor dimensionality reduction (MDR), and classification and regression tree (CART) analyses to explore high-order gene–gene interactions among the functional SNPs to ADHD risks. The results indicated that interactions among the PER1 rs2518023, ARNTL2 rs2306074 and NR1D1 rs939347 were associated with the risk of ADHD in children. Individuals carrying the combination genotypes of the PER1 rs2518023 GG or GT, ARNTL2 rs2306074 TC or TT and NR1D1 rs939347 GA or AA displayed a significantly higher risk for ADHD than who carry the PER1 rs2518023 TT and CRY2 rs2292910 CA/CC genotypes (adjusted OR = 4.37, 95% CI = 2.16–8.85, P < 0.001).ConclusionsThese findings revealed the importance of genetic variations related to the circadian clock system to the susceptibility of children ADHD.     

Focal EEG abnormalities might reflect neuropathological characteristics of pervasive developmental disorder and attention-deficit/hyperactivity disorder

Neurophysiological characteristics in electroencephalograms (EEG) were investigated for patients with pervasive developmental disorder (PDD) and for patients with attention-deficit/hyperactivity disorder (AD/HD). This study examined 64 PDD children and 22 AD/HD children with no history of epilepsy or progressive neurological or psychiatric disorder. We used multivariate analysis to compare EEG abnormalities, clinical symptoms, and intelligence levels between PDD and AD/AD patient groups. Paroxysmal discharges at the frontopolar-frontal (Fp-F) brain regions and background EEG abnormalities tended to be detected preferentially in the PDD group, although paroxysmal discharges at central-temporal (C-T) regions tended to be detected preferentially in the AD/HD group. The paroxysmal discharges observed in patients expressing persistence and impulsivity are apparently localized respectively in the Fp-F and C-T regions. A combination of EEG abnormalities, including background EEG abnormalities and paroxysmal discharges at Fp-F and C-T regions, might be useful diagnostic hallmarks to distinguish PDD with AD/HD from AD/HD alone using a logistic regression model. The dysfunction of specific brain areas associated with EEG abnormalities might explain characteristics of clinical symptoms observed in PDD and AD/HD patients.     

Proton spectroscopy in medication-free pediatric attention-deficit/hyperactivity disorder.

BACKGROUND: The frontal-striatal pathway has been previously implicated in the neuropathology of attention-deficit/hyperactivity disorder (ADHD). Hence, we used proton magnetic resonance spectroscopy (1H-MRS) to examine metabolite levels in the prefrontal cortex of children with ADHD. METHODS: Nine age- and gender-matched case-control pairs were examined, ages 7 to 16 years. A long-echo 1H-MRS scan was acquired from the right prefrontal cortex and left striatum in all subjects. Compounds that can be visualized with 1H-MRS include N-acetyl-aspartate (NAA), glutamate/glutamine/gamma-aminobutyric acid (Glx), creatine/phosphocreatine (Cr), and choline compounds (Cho). RESULTS: Frontal-striatal glutamatergic resonances were elevated in the children with ADHD as compared to healthy control subjects. No differences were noted in NAA, Cho, or Cr metabolite ratios. CONCLUSIONS: These findings suggest that frontal-striatal Glx resonances may be increased in children with ADHD in comparison with healthy control subjects.     

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.     

Rodent models of attention-deficit/hyperactivity disorder.

An ideal animal model should be similar to the disorder it models in terms of etiology, biochemistry, symptomatology, and treatment. Animal models provide several advantages over clinical research: simpler nervous systems, easily interpreted behaviors, genetic homogeneity, easily controlled environment, and a greater variety of interventions. Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder of childhood onset that is characterized by inattentiveness, hyperactivity, and impulsiveness. Its diagnosis is behaviorally based; therefore, the validation of an ADHD model must be based in behavior. An ADHD model must mimic the fundamental behavioral characteristics of ADHD (face validity), conform to a theoretical rationale for ADHD (construct validity), and predict aspects of ADHD behavior, genetics, and neurobiology previously uncharted in clinical settings (predictive validity). Spontaneously hypertensive rats (SHR) fulfill many of the validation criteria and compare well with clinical cases of ADHD. Poor performers in the five-choice serial reaction time task and Naples high-excitability rats (NHE) are useful models for attention-deficit disorder. Other animal models either focus on the less important symptom of hyperactivity and might be of limited value in ADHD research or are produced in ways that would not lead to a clinical diagnosis of ADHD in humans, even if ADHD-like behavior is displayed.     

Shifting-related brain magnetic activity in attention-deficit/hyperactivity disorder.

BACKGROUND: Current theories suggest a role for frontal-striatal circuits in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). METHODS: We used magnetoencephalography (MEG) to measure event-related brain activity during a simplified version of the Wisconsin Card Sorting Test in children with DSM-IV combined type ADHD (ADHD-C) or predominantly inattentive type ADHD (ADHD-PI) and in age- and intelligence-matched control children. RESULTS: In control children, set-shifting cues evoked a higher degree of activation in the medial temporal lobe (MTL) between 200 and 300 msec than non-shifting cues, with MTL activation predicting later activity in left anterior cingulate cortex (ACC) (at 400-500 msec). This MTL-ACC response pattern was diminished in children with ADHD. By contrast, children with ADHD showed early activity in regions barely activated in control children, such as left inferior parietal lobe and posterior superior temporal gyrus. CONCLUSIONS: These preliminary data support theories of frontal dysfunction in ADHD but also suggest that deficits in higher-level functions might be secondary to disruptions in earlier limbic processes.     

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.     

Psychiatric pharmacogenetics: personalizing psychostimulant therapy in attention-deficit/hyperactivity disorder

There is a substantial amount of variation in response and adverse drug reactions to psychostimulant therapy in attention-deficit/hyperactivity disorder (ADHD). Psychiatric pharmacogenetics is a rapidly developing field, which can be applied to identify genetic predictors of this variability in outcome to psychostimulant medications. This article will briefly review ADHD and its pharmacotherapy. This will be followed by an overview of the pharmacokinetics and pharmacodynamics of methylphenidate, the most commonly used psychostimulant in the US. Then the field of psychiatric pharmacogenetics will be introduced and its methodology will be described. This will be followed by a discussion about how pharmacogenetics can be applied to children afflicted with ADHD. The future of psychiatric pharmacogenetics will then be presented with an emphasis being placed on developing prospects that will ensure the continued advancement of this field.     

Patterns and predictors of attention-deficit/hyperactivity disorder persistence into adulthood: results from the national comorbidity survey replication.

BACKGROUND: Despite growing interest in adult attention-deficit/hyperactivity disorder (ADHD), little is known about predictors of persistence of childhood cases into adulthood. METHODS: A retrospective assessment of childhood ADHD, childhood risk factors, and a screen for adult ADHD were included in a sample of 3197 18-44 year old respondents in the National Comorbidity Survey Replication (NCS-R). Blinded adult ADHD clinical reappraisal interviews were administered to a sub-sample of respondents. Multiple imputation (MI) was used to estimate adult persistence of childhood ADHD. Logistic regression was used to study retrospectively reported childhood predictors of persistence. Potential predictors included socio-demographics, childhood ADHD severity, childhood adversity, traumatic life experiences, and comorbid DSM-IV child-adolescent disorders (anxiety, mood, impulse-control, and substance disorders). RESULTS: Blinded clinical interviews classified 36.3% of respondents with retrospectively assessed childhood ADHD as meeting DSM-IV criteria for current ADHD. Childhood ADHD severity and childhood treatment significantly predicted persistence. Controlling for severity and excluding treatment, none of the other variables significantly predicted persistence even though they were significantly associated with childhood ADHD. CONCLUSIONS: No modifiable risk factors were found for adult persistence of ADHD. Further research, ideally based on prospective general population samples, is needed to search for modifiable determinants of adult persistence of ADHD.     

Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review.

One of the most prominent neuropsychologic theories of attention-deficit/hyperactivity disorder (ADHD) suggests that its symptoms arise from a primary deficit in executive functions (EF), defined as neurocognitive processes that maintain an appropriate problem-solving set to attain a later goal. To examine the validity of the EF theory, we conducted a meta-analysis of 83 studies that administered EF measures to groups with ADHD (total N = 3734) and without ADHD (N = 2969). Groups with ADHD exhibited significant impairment on all EF tasks. Effect sizes for all measures fell in the medium range (.46-.69), but the strongest and most consistent effects were obtained on measures of response inhibition, vigilance, working memory, and planning. Weaknesses in EF were significant in both clinic-referred and community samples and were not explained by group differences in intelligence, academic achievement, or symptoms of other disorders. ADHD is associated with significant weaknesses in several key EF domains. However, moderate effect sizes and lack of universality of EF deficits among individuals with ADHD suggest that EF weaknesses are neither necessary nor sufficient to cause all cases of ADHD. Difficulties with EF appear to be one important component of the complex neuropsychology of ADHD.     

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.     

Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder.

BACKGROUND: Although abnormalities in reward processing have been proposed to underlie attention-deficit/hyperactivity disorder (ADHD), this link has not been tested explicitly with neural probes. METHODS: This hypothesis was tested by using fMRI to compare neural activity within the striatum in individuals with ADHD and healthy controls during a reward-anticipation task that has been shown previously to produce reliable increases in ventral striatum activity in healthy adults and healthy adolescents. Eleven adolescents with ADHD (5 off medication and 6 medication-na?ve) and 11 healthy controls (ages 12-17 y) were included. Groups were matched for age, gender, and intelligence quotient. RESULTS: We found reduced ventral striatal activation in adolescents with ADHD during reward anticipation, relative to healthy controls. Moreover, ventral striatal activation was negatively correlated with parent-rated hyperactive/impulsive symptoms across the entire sample. CONCLUSIONS: These findings provide neural evidence that symptoms of ADHD, and impulsivity or hyperactivity in particular, may involve diminished reward anticipation, in addition to commonly observed executive dysfunction.