Children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder: an EEG analysis

This study investigated EEG differences between two groups of children with attention-deficit/hyperactivity disorder combined type (ADHD), with or without comorbid oppositional defiant disorder (ODD), and normal control subjects. Each group consisted of 20 males. All subjects were between the ages of 8 and 12 years, and groups were matched on age. EEG was recorded during an eyes-closed resting condition from 21 monopolar derivations, which were clustered into nine regions for analysis. The EEGs were Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. Values were also calculated for the theta/alpha and theta/beta ratios. The ADHD groups had more absolute and relative theta than the control group. Regionally, the ADHD groups had less relative alpha and more relative delta in posterior regions, and less relative beta in the frontal regions, than the control group. These differences were also apparent in both ratio measures. Only two significant topographic differences were found between the ADHD groups, with both of these being less deviant from normality in the ADHD+ODD group than the ADHD group. These results indicate that EEG correlates of ADHD are not clouded by the presence of comorbid ODD, which suggests possible applications in clinical practice.     

Atomoxetine treatment in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder

OBJECTIVE: To examine (1) moderating effects of oppositional defiant disorder (ODD) on attention-deficit/hyperactivity disorder (ADHD) treatment response and (2) responses of ODD symptoms to atomoxetine. METHOD: Children and adolescents (ages 8-18) with ADHD were treated for approximately 8 weeks with placebo or atomoxetine (fixed dosing: 0.5, 1.2, or 1.8 mg/kg/day, b.i.d.) under randomized, double-blind conditions. Among patients with lifetime diagnostic information (n = 293), 39% were diagnosed with comorbid ODD and 61% were not. Treatment-group differences and differences between patients with and without comorbid ODD were examined post hoc for changes on the Attention-Deficit/Hyperactivity Disorder Rating Scale IV-Parent version, investigator-administered and -scored; Conners' Parent Rating Scale-Revised Short Form; Clinical Global Impressions Severity of ADHD Scale; and the parent-rated Child Health Questionnaire. RESULTS: Youths with ADHD and comorbid ODD showed statistically significant improvement in ADHD, ODD, and quality-of-life measures. Treatment response was similar in youths with and without ODD, except that the comorbid group showed improvement compared with placebo at 1.8 mg/kg/day but not 1.2 mg/kg/day. In contrast, youths without ODD showed improvement at 1.2 mg/kg/day and no incremental benefit at 1.8 mg/kg/day. CONCLUSIONS: Atomoxetine treatment improves ADHD and ODD symptoms in youths with ADHD and ODD, although the comorbid group may require higher doses.     

Psychosocial problems in attention-deficit hyperactivity disorder with oppositional defiant disorder

The purpose of this study is to clarify psychosocial characteristics of the comorbidity of attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in comparison with ADHD or ODD alone. Thirty-one patients with ADHD comorbid with ODD were compared with 23 ADHD alone and 10 with ODD alone, in terms of various examination items including objective assessment scales. The comorbid group demonstrated higher Children Depression Inventory score and State-Trait Anxiety Inventory for Children (state-anxiety) score than the ADHD or the ODD group, possessing more problems in the relationship with teachers than the ADHD group, with friends more than the ADHD or the ODD group, and with their mothers more than the ADHD group and less than the ODD group. School refusal occurred more frequently in the comorbid group than the ADHD group and less than the ODD group. The comorbid group had more psychosocial problems than the ADHD group and the ODD group. These problems could be classified into three types: (i) those derived from ODD, problems in the relationship with teachers; (ii) those derived from ODD but reduced by the coexistence of ADHD, problems in the relationship with their mothers; and (iii) those resulting from the comorbidity of ADHD and ODD, problems in the relationship with friends and anxious and depressive tendency. The difficulties in the relationship with teachers and friends observed in the comorbid group may lead to school refusal.     

The influence of comorbid oppositional defiant disorder on white matter microstructure in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are highly comorbid disorders. ADHD has been associated with altered white matter (WM) microstructure, though the literature is inconsistent, which may be due to differences in the in- or exclusion of participants with comorbid ODD. WM abnormalities in ODD are still poorly understood, and it is unclear whether comorbid ODD in ADHD may have confounded the current ADHD literature. Diffusion Tensor Imaging (DTI) was used to compare fractional anisotropy (FA) and mean diffusivity (MD) between ADHD patients with (n = 42) and without (n = 117) comorbid ODD. All participants were between 8–25 years and groups did not differ in mean age or gender. Follow-up analyses were conducted to examine the role of antisocial behaviour (conduct problems) on FA and MD values in both groups. Comorbid ODD in ADHD was associated with lower FA in left frontotemporal WM, which appeared independent of ADHD symptoms. FA was negatively associated with antisocial behaviour in ADHD + ODD, but not in ADHD-only. Comorbid ODD is associated with WM abnormalities in individuals with ADHD, which appears to be independent of ADHD symptoms. Altered WM microstructure in comorbid ODD may play a role in inconsistencies in the current DTI literature in ADHD. Altered development of these tracts may contribute to social-emotional and cognitive problems in children with oppositional and antisocial behaviour.     

Attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder or conduct disorder

Comorbid oppositional defiant disorder (ODD) and conduct disorder (CD) are common in clinically referred children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Early recognition and treatment of co-occurring ADHD and ODD and/or CD is important because comorbidity influences symptom severity, prognosis, and treatment. Research on treatment supports the importance of behavior therapies for ODD and multimodal psychosocial interventions delivered simultaneously and intensively for CD with adjunctive medication for ADHD symptoms. Clinical trials are beginning to show that stimulants and atomoxetine are effective for ADHD and ODD symptoms when the disorders occur together. It is presently unclear if ODD in the absence of ADHD responds to pharmacotherapy. More research is needed examining the effects of commonly prescribed ADHD medications on CD symptoms. Research suggests a high prevalence of lifetime comorbidity with ODD in clinically referred patients with ADHD.     

Medication refusal in children with oppositional defiant disorder or conduct disorder and comorbid attention-deficit/hyperactivity disorder: medication history and clinical correlates

Abstract Objective: This study examines the characteristics of 96 children with attention-deficit/hyperactivity disorder (ADHD) and their families who refused a recommendation for medication as part of their treatment for disruptive disorders. Methods: The ADHD cases were taken from a sample of 139 youth (age 6-11) who were recruited for a clinical trial that compared the administration of a modular psychosocial treatment in an outpatient clinic or community settings. Medication management was an optional treatment module for children with ADHD in both conditions. Children who were (vs. were not) taking medication at intake, and children who accepted (vs. refused) medication recommendations during the study were compared on diagnostic and clinical measures related to child, school, parent, and family domains of functioning. Results: Parents of 30% of the children refused study medication for ADHD. Parental medication acceptability and intake correlated highly with both medication history and study refusal of medication. Increased parental self-efficacy and emotional support for their youth correlated with medication refusal. No demographics and few child or school factors were associated with medication refusal. Medication use was associated with reductions in some key ADHD symptoms, but did not affect disruptive behaviors as did the psychosocial interventions. Conclusion: Medication refusers remain poorly understood but certain correlates, such as parental self-efficacy, parental emotional support for their youth, and medication acceptability, warrant further evaluation.     

The distribution of symptoms of attention-deficit/hyperactivity disorder and oppositional defiant disorder in school age children in Turkey

Abstract Objective The aim of this study was to determine the prevalence of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in school age children in Sivas province centre and to examine the distribution of symptoms according to subtypes. Method The study population was made up of 1425 children between the ages of 6 and 15 from eight primary schools selected by random sampling method in Sivas province centre. All students were given a questionnaire prepared according to DSMIV criteria that was completed by their parents or teachers. This form includes 18 symptoms of ADHD and eight symptoms of ODD. Students t-test and variance analysis were used for statistical evaluation. Results A prevalence of 8.1% was found for ADHD in our study. According to subtypes, 32.2% of these were inattentive, 40% were hyperactive and 27.8% were combined type. A prevalence of 11.5% was found for ODD. The boy/girl ratio was > 1 for both ADHD and ODD, and 52.2% of those with ADHD were established as having ODD at the same time. Conclusions The prevalence of ADHD and ODD in primary school children was not considered to be small. Studies concerning the distribution of symptoms in different societies, cultures, and viewpoints and identification of children with this type of problem are beneficial for early diagnosis and prophylactic treatment.     

Executive functioning deficits in attention-deficit/hyperactivity disorder are independent of oppositional defiant or reading disorder.

OBJECTIVE: To evaluate deficits of executive functions in children with attention-deficit/hyperactivity disorder (ADHD) classified by type (combined [CT] or predominantly inattentive [IT]) and comorbidity with oppositional defiant disorder (ODD) and reading disorder (RD). METHOD: The Wisconsin Card Sorting Test (WCST) and Tower of Hanoi (TOH) were administered to 28 community volunteers and 359 children (7.5-13.5 years old) divided into ADHD types, RD, and ODD. RESULTS: ADHD/CT children solved fewer puzzles and violated more rules on the TOH than ADHD/IT or non-ADHD subjects. On the WCST there were no differences between diagnostic samples in perseverativeness, but ADHD/CT patients made more nonperseverative errors than ADHD/IT children. ODD was associated with moderately better TOH performance and RD with excessive rule breaks. CONCLUSIONS: Executive functioning deficits were found for only ADHD/CT children and were independent of comorbidity with RD or ODD.     

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.     

Altered brain morphology in boys with attention deficit hyperactivity disorder with and without comorbid conduct disorder/oppositional defiant disorder

About 50% of attention deficit hyperactivity disorder (ADHD) patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure (ADHD‐only) and comorbid ADHD (ADHD+ODD/CD). Therefore, we aimed to investigate the structural profile of ADHD‐only versus ADHD+ODD/CD spanning the indices subcortical and cortical volume, cortical thickness, and surface area. We predicted a reduced total gray matter, striatal, and cerebellar volume in both patient groups and a reduced amygdalar and hippocampal volume for ADHD+ODD/CD. We also explored alterations in prefrontal volume, thickness, and surface area. We acquired structural images from an adolescent sample ranging from 11 to 17 years, matched with regard to age, pubertal status, and IQ—including 36 boys with ADHD‐only, 26 boys with ADHD+ODD/CD, and 30 typically developing (TD) boys. We analyzed structural data with FreeSurfer. We found reductions in total gray matter and total surface area for both patient groups. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged. We demonstrate the necessity to carefully differentiate between ADHD and ADHD+ODD/CD. The increased rostral middle frontal thickness might hint at a delayed adolescent cortical thinning in ADHD+ODD/CD. Patients with the double burden ADHD and ODD or CD seem to be even more affected than patients with pure ADHD.     

Quantitative EEG in low-IQ children with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study investigated EEG differences between children with attention-deficit/hyperactivity disorder (AD/HD) and matched control subjects, with either normal or low IQs. METHODS: Twenty normal-IQ and 20 low-IQ children with AD/HD, and 40 age-, IQ- and sex-matched control subjects participated in this study. EEG was recorded from 21 sites during an eyes-closed resting condition and Fourier transformed to provide estimates for total power, and absolute and relative power in the delta, theta, alpha and beta bands. RESULTS: Children with AD/HD had increased theta activity with decreased levels of alpha and beta activity compared to control subjects. IQ was not found to impact on the EEG. No significant differences were found between subjects with normal and low IQs, with the low- and high-IQ AD/HD groups having similar EEG profiles. CONCLUSIONS: Low-IQ children with AD/HD have similar EEG abnormalities to those with normal IQs, and IQ does not appear to impact on EEG power measures. SIGNIFICANCE: This is the first study to investigate EEG differences in low-IQ children with and without AD/HD.     

Differential stimulant response on attention in children with comorbid anxiety and oppositional defiant disorder

Attention-deficit hyperactivity disorder (ADHD) affects 3% to 7% of school-age children. Approximately 30% of the children with ADHD also have comorbid anxiety or oppositional defiant disorder. Methylphenidate is the drug of choice for the medical treatment of such cases. When compared with children with ADHD alone, children with comorbid anxiety or oppositional defiant disorder may show worsening of the global attention score in response to methylphenidate and not only a "reduced response," as reported in previous studies. This study included 1122 children diagnosed as ADHD, of which 174 were diagnosed with comorbid anxiety and 141 with comorbid oppositional defiant disorder. All patients performed the Test of Variables of Attention before and after methylphenidate administration. A normal distribution (Gaussian distribution) of reaction to methylphenidate, as measured by the global ADHD score in children diagnosed as pure ADHD, was found. These findings were in contrast to children with ADHD and comorbid anxiety or oppositional defiant disorder who showed a bimodal distribution and hence represent a distinct population. In both groups with comorbid disorders, there was a larger subgroup in which significant worsening of global ADHD score occurred after methylphenidate administration (P < .05). Children with ADHD and comorbid anxiety or oppositional defiant disorder might represent clinically distinct populations in which inattention is secondary to those disorders; therefore, methylphenidate may be an inappropriate treatment for such children.     

Methylphenidate in children with oppositional defiant disorder and both comorbid chronic multiple tic disorder and ADHD

Our primary objective was to determine if immediate-release methylphenidate is an effective treatment for oppositional defiant disorder diagnosed from mother's report in children with both chronic multiple tic disorder and attention-deficit hyperactivity disorder (ADHD). Children (n = 31) aged 6 to 12 years received placebo and 3 doses of methylphenidate twice daily for 2 weeks each under double-blind conditions and were assessed with ratings scales and laboratory measures. Results indicated significant improvement in both oppositional and ADHD behaviors with medication; however, the magnitude of treatment effect varied considerably as a function of disorder (ADHD > Oppositional behaviors), informant (teacher > mother), assessment instrument, and specific oppositional behavior (rebellious > disobeys rules). Drug response was comparable with that in children (n = 26) who did not have diagnosed oppositional defiant disorder, but comorbidity appeared to alter the perceived benefits for ADHD according to mother's report. Methylphenidate is an effective short-term treatment for oppositional behavior in children with comorbid ADHD and chronic multiple tic disorder.     

EEG activity in girls with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study investigated the EEG of girls with Attention-deficit/hyperactivity disorder (ADHD). METHODS: Subjects consisted of 100 girls with ADHD between the ages of 8 and 12 years and 40 age- and gender-matched controls. EEG was recorded from 21 sites during an eyes-closed resting condition and Fourier transformed to provide estimates for total power, and relative power in the delta, theta, alpha and beta bands. Factor analysis was used to group sites into 3 regions, covering frontal, central and posterior regions. The total ADHD group was compared to the control group as well as the data being subjected to cluster analysis. RESULTS: The ADHD subjects had greater total power, more relative theta, and less relative delta, alpha and beta than controls. Cluster analysis indicated the presence of two distinct EEG clusters of girls with ADHD. These were (a) a large subgroup characterized by increased total power, more relative theta, and less relative delta and beta than control subjects; and (b) a small subgroup with a substantially-increased amount of high amplitude theta activity, with deficiencies in all other bands. CONCLUSIONS: These results indicate that girls with ADHD exhibit abnormalities in their EEGs, but there is far less variance in their EEG profiles than is found in boys with the disorder. The results also suggest that there may be distinct groups of girls with ADHD who are not being referred for clinical treatment. Recommendations are made for further research in this population. This study is significant in that it is the first major study to separately investigate the EEG of girls with ADHD.     

Age and gender effects in EEG coherence: III. Girls with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study investigated intrahemispheric and interhemispheric EEG coherences as a function of age in girls with different DSM-IV subtypes of Attention-Deficit/Hyperactivity Disorder (AD/HD). It completes a series of 3 studies aimed at clarifying developmental and gender impacts on the coupling between brain regions in this disorder. METHODS: Three groups of 40 children (AD/HD combined type, AD/HD inattentive type, and normal controls) participated. Each group contained 8 females in each of 5, 1-year age bands from 8 to 12 years. EEG was recorded from 21 sites during an eyes-closed resting condition. Wave-shape coherence was calculated for 8 intrahemispheric electrode pairs (4 in each hemisphere), and 8 interhemispheric electrode pairs, within each of the delta, theta, alpha and beta bands. RESULTS: Developmental effects in intrahemispheric coherences at shorter and longer inter-electrode distances were not as predicted by Thatcher's two-compartment model, contrary to previous findings in boys. Females with AD/HD showed evidence of developmental delay and widespread anomalous elevations in coherence. Girls with AD/HD of the combined type showed similar but greater anomalies than girls with AD/HD of the inattentive type. CONCLUSIONS: Girls with AD/HD show coherence anomalies relative to age- and gender-matched controls, which differ substantially from those shown by boys with AD/HD. These coherence anomalies did not differ in nature between girls with different DSM-IV subtypes of AD/HD, suggesting that subtype differences in girls reflect only symptom severity. SIGNIFICANCE: The data reported here indicate qualitative differences in EEG coherences in girls with AD/HD compared with controls, and quantitative differences between girls with different subtypes of AD/HD. Both sets of effects differ in nature from those previously found in boys with AD/HD, showing the need to carefully consider gender in future studies of AD/HD.     

Children with attention-deficit/hyperactivity disorder and autistic features: EEG evidence for comorbid disorders

Attention-deficit/hyperactivity disorder (AD/HD) is the most common psychiatric disorder of childhood, although AD/HD is rarely the only diagnosis given to these children. Within the literature there is some debate as to whether it is valid to diagnose AD/HD with autism as a comorbid disorder, since the present diagnostic systems exclude the diagnosis of both disorders in the same child. The aim of this study was to determine whether electroencephalography (EEG) differences exist between two groups of children diagnosed with AD/HD, one scoring high (AD/HD+) and one scoring low (AD/HD?) on a measure of autism. The EEG was recorded during an eyes-closed resting condition from 19 electrodes, and Fourier transformed to provide absolute and relative power estimates in delta, theta, alpha and beta bands. Compared to age- and sex-matched controls, the AD/HD? group had increased absolute power in all frequency bands, somewhat higher relative theta activity and decreased relative delta. In comparison to the AD/HD? group, patients with autistic features (AD/HD+) had a number of qualitative differences in the beta and theta bands. These results indicate the presence of two comorbid conditions in the AD/HD+ group, which suggests that AD/HD and autism can occur in the same individual.     

Comorbid oppositional defiant disorder and the risk of relapse during 9 months of atomoxetine treatment for attention-deficit/hyperactivity disorder

OBJECTIVE: To examine the influence of comorbid oppositional defiant disorder (ODD) on the relative risk (RR) of relapse during 9 months of treatment with atomoxetine for attention-deficit/hyperactivity disorder (ADHD). METHOD: Four hundred and sixteen children and adolescents with ADHD whose symptoms remitted during initial 10-week, open-label atomoxetine treatment were randomly assigned to continue with atomoxetine or placebo. RESULTS: In all, 43% met criteria for comorbid ODD. A total of 17% of patients with comorbid ODD relapsed (CGI-Severity score >or= 3 and ADHD Rating Scale total score of 90% or more of baseline at study entry on two consecutive visits) during atomoxetine treatment, compared with 26% of patients without comorbid ODD (RR 0.67, 95% CI 0.42-1.06). Mean time to relapse was not significantly different [mean (SE) days to relapse, ADHD/ +ODD: 215 (7.38); ADHD/-ODD: 211 (7.61); log rank p = 0.08]. This finding is placed within the context of atomoxetine affording an overall protection against relapse compared with placebo (RR 0.59, 95% CI 0.43-0.80). CONCLUSIONS: Comorbid ODD does not influence the rate of relapse of patients with ADHD during longer-term treatment with atomoxetine. Atomoxetine protects against the relapse of ADHD symptoms regardless of the presence or absence of comorbid ODD.     

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.