Morning and evening behavior in children and adolescents treated with atomoxetine once daily for Attention-Deficit/Hyperactivity Disorder (ADHD): Findings from two 24-week, open-label studies

Background  

The impact of once daily atomoxetine treatment on symptoms in children and adolescents with ADHD may vary over the day. In order to capture such variations, two studies were undertaken in children and adolescents with ADHD using two instruments that capture morning and evening behavior and ADHD-related difficulties over the day. This secondary measure analysis builds on two primary analyses that were conducted separately for children and adolescents and also published separately.     

The behavioural profile of children with attention-deficit/hyperactivity disorder and of their siblings

The behavioural profiles in N = 69 index children with attention-deficit/hyperactivity disorder (ADHD), N = 32 siblings with ADHD, N = 35 siblings without ADHD, and N = 36 normal controls were compared by the use of standardized parent and teacher rating scales. The four groups were matched by age and IQ. The behavioural profiles of the two ADHD groups were very similar not only in the behavioural domains of ADHD, but also in scales measuring emotional and conduct problems. Siblings without ADHD shared more similarities with normal controls except for more emotional problems. These general trends were stronger in the parent compared to the teacher ratings. These findings indicate that not only ADHD-related but also other behaviours show a strong family aggregation. The informant differences may reflect context dependent differences in child behaviour and contrast effects particularly in parental ratings.     

Reboxetine versus methylphenidate in treatment of children and adolescents with attention deficit-hyperactivity disorder

Background and purpose  

Attention deficit-hyperactivity disorder (ADHD) is a common psychiatric diagnosis among children and adolescents. This study has been conducted to evaluate the efficacy and tolerability of reboxetine in comparison with methylphenidate in treatment of children and adolescents with ADHD.     

Sequence analysis of <Emphasis Type="Italic">Drd2</Emphasis>, <Emphasis Type="Italic">Drd4</Emphasis>, and <Emphasis Type="Italic">Dat1</Emphasis> in SHR and WKY rat strains

Background  

The Spontaneously Hypertensive Rat (SHR) shows a number of behaviours that closely parallel those seen in children with attention-deficit hyperactivity disorder. These include motor hyperactivity, excessive responses under a fixed-interval/extinction schedule, difficulty in acquiring operant tasks and increased sensitivity to immediate behavioural reinforcement. As in children with ADHD, the behavioural and cognitive deficits in the SHR are responsive to stimulants, including d-amphetamine and d,l-methylphenidate. The non-hyperactive Wistar Kyoto (WKY) rat strain is often used as a control in behavioural studies of the SHR, and WKY itself has been suggested to be a useful animal model of depression. Numerous studies have shown that dopaminergic neurotransmission is altered between the two strains. Human genetic studies have found associations between several dopaminergic genes and both ADHD and depression.     

Attention deficit hyperactivity disorder (ADHD) in phenotypically similar neurogenetic conditions: Turner syndrome and the RASopathies

Background

ADHD (attention deficit hyperactivity disorder) is a common neurodevelopmental disorder. There has been extensive clinical and basic research in the field of ADHD over the past 20 years, but the mechanisms underlying ADHD risk are multifactorial, complex and heterogeneous and, as yet, are poorly defined. In this review, we argue that one approach to address this challenge is to study well-defined disorders to provide insights into potential biological pathways that may be involved in idiopathic ADHD.

Main body

To address this premise, we selected two neurogenetic conditions that are associated with significantly increased ADHD risk: Turner syndrome and the RASopathies (of which Noonan syndrome and neurofibromatosis type 1 are the best-defined with regard to ADHD-related phenotypes). These syndromes were chosen for two main reasons: first, because intellectual functioning is relatively preserved, and second, because they are strikingly phenotypically similar but are etiologically distinct. We review the cognitive, behavioural, neural and cellular phenotypes associated with these conditions and examine their relevance as a model for idiopathic ADHD.

Conclusion

We conclude by discussing current and future opportunities in the clinical and basic research of these conditions, which, in turn, may shed light upon the biological pathways underlying idiopathic ADHD.

     

Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

Background

Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions.

Methods

We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups.

Results

Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD.

Limitations

This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small.

Conclusion

Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD.     

Effects of early life trauma are dependent on genetic predisposition: a rat study

Background  

Trauma experienced early in life increases the risk of developing a number of psychological and/or behavioural disorders. It is unclear, however, how genetic predisposition to a behavioural disorder, such as attention-deficit/hyperactivity disorder (ADHD), modifies the long-term effects of early life trauma. There is substantial evidence from family and twin studies for susceptibility to ADHD being inherited, implying a strong genetic component to the disorder. In the present study we used an inbred animal model of ADHD, the spontaneously hypertensive rat (SHR), to investigate the long-term consequences of early life trauma on emotional behaviour in individuals predisposed to developing ADHD-like behaviour.     

Atomoxetine treatment and ADHD-related difficulties as assessed by adolescent patients, their parents and physicians

Background  

The degree of ADHD-related difficulties – reflecting overall impairment, social functioning, and quality of life – may be perceived differently by adolescent patients, parents and physicians. The primary aim of this study was to investigate ADHD-related difficulties during atomoxetine treatment, as perceived by the three different raters. Secondary objectives focused on effectiveness and tolerability of atomoxetine treatment in a population of adolescent patients with ADHD.     

MEG event-related desynchronization and synchronization deficits during basic somatosensory processing in individuals with ADHD

Background  

Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent, complex disorder which is characterized by symptoms of inattention, hyperactivity, and impulsivity. Convergent evidence from neurobiological studies of ADHD identifies dysfunction in fronto-striatal-cerebellar circuitry as the source of behavioural deficits. Recent studies have shown that regions governing basic sensory processing, such as the somatosensory cortex, show abnormalities in those with ADHD suggesting that these processes may also be compromised.     

Behavioral variability, elimination of responses, and delay-of-reinforcement gradients in SHR and WKY rats

Background  

Attention-deficit/hyperactivity disorder (ADHD) is characterized by a pattern of inattention, hyperactivity, and impulsivity that is cross-situational, persistent, and produces social and academic impairment. Research has shown that reinforcement processes are altered in ADHD. The dynamic developmental theory has suggested that a steepened delay-of-reinforcement gradient and deficient extinction of behavior produce behavioral symptoms of ADHD and increased behavioral variability.     

How do ADHD children perceive their cognitive, affective, and behavioral aspects of anger expression in school setting?

Background  

Anger is an ignored research area in children and young adolescents with Attention deficit hyperactivity disorder (ADHD) in the school setting. This study compares school anger dimensions in children and young adolescents with ADHD and a control group.     

Moment-to-moment dynamics of ADHD behaviour

Background  

The behaviour of children with Attention-Deficit / Hyperactivity Disorder is often described as highly variable, in addition to being hyperactive, impulsive and inattentive. One reason might be that they do not acquire complete and functional sequences of behaviour. The dynamic developmental theory of ADHD proposes that reinforcement and extinction processes are inefficient because of hypofunctioning dopamine systems, resulting in a narrower time window for associating antecedent stimuli and behaviour with its consequences. One effect of this may be that the learning of behavioural sequences is delayed, and that only short behavioural sequences are acquired in ADHD. The present study investigated acquisition of response sequences in the behaviour of children with ADHD.     

Five-year predictive validity of DSM-IV conduct disorder research diagnosis in 4½–5-year-old children

Objective

This longitudinal study of a non-referred, population-based sample tested the 5-year predictive validity of the DSM-IV conduct disorder (CD) research diagnosis in children 4½–5 years of age.

Method

In the E-Risk Study, a representative birth cohort of 2,232 children, mothers were interviewed and teachers completed mailed questionnaires to assess children’s past 6-month CD symptoms. A follow-up assessment was conducted when children were 10 years old.

Results

CD-diagnosed 5-year-olds were significantly more likely than controls to have behavioural and educational difficulties at age 10. Increased risk for age-10 educational difficulties persisted after controlling for age-5 IQ and ADHD diagnosis. Although the majority of CD-diagnosed 5-year-olds had no CD symptoms at age 10, findings suggest that these “remitted” children continued to experience behavioural and educational problems 5 years later despite their apparent remission from CD.

Conclusions

DSM-IV CD symptoms validly identify preschool-aged children who continue to have behavioural and educational problems in middle-childhood.     

Electrophysiological evidence for abnormal preparatory states and inhibitory processing in adult ADHD

Background  

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that starts in childhood and frequently persists in adults. Several theories postulate deficits in ADHD that have effects across many executive functions or in more narrowly defined aspects, such as response inhibition. Electrophysiological studies on children, however, indicate that ADHD is not associated with a core deficit of response inhibition, as abnormal inhibitory processing is typically preceded or accompanied by other processing deficits. It is not yet known if this pattern of abnormal processing is evident in adult ADHD.     

Attention deficit disorder: multidisciplinary observational study over 1 year

Introduction

In France, attention deficit disorder (ADHD) has traditionally met with two opposing approaches (biological and psychoanalytic). This conflict led us to conduct a multidisciplinary observational study, on a group of 36 children over a period of 1 year.

Methods

Thirty-six children with ADHD diagnostic (DSM IV), not treated by MPH were included. Initial “multi-field” evaluation (T0) consisted of: neuro-paediatric consultation (Conners questionnaire, Child Behaviour Checklist, reading and writing scores by French tests); semi-structured child psychiatric interview (DSM-IV axis I), structural hypothesis (CFTMEA), existence of narcissistic fragility, parents/child interactions; neuropsychological standardized evaluation (attention and executive functions); psychodynamic interview and projective tests (Rorscharch, CAT or TAT). A therapeutic project is proposed combining MPH and psychotherapy according to the results. A new evaluation 1 year later (T1) included a consultation and a neuropsychological evaluation.

Results T0

All parental questionnaires appreciating attention deficit and hyperactivity/impulsivity were significantly pathological. The neuropsychological evaluation showed usual characteristics of ADHD with individual differences. The psychiatric evaluation revealed the frequency of comorbidity in axis I (23% of children with more than two diagnoses, 57% with anxiety disorder, 23 and 3% with oppositional and conduct disorder).

Follow up (T1)

Thirty-one children were re-examined (20 treated by MPH and 11 not treated because of parental refusal or particular psychopathological situations). Psychoanalytical psychotherapy, proposed to 28 children, was undertaken with only 19. An improvement in scores for attention and executive tests was registered only in the treated group.

Discussion

The tests confirm deficits of attention and executive functions without correlation with the scores of questionnaires, underlining the need for a neuropsychological evaluation to objectify attention disorders. Projective tests refine and enrich psychiatric evaluation and showed that half of the children had borderline organization. However, structural hypotheses were heterogeneous, suggesting the need for specific therapeutic projects to be devised according to each child. The treated children were the only ones to improve attention deficit. On the other hand, the scores of anxiety are not improved by MPH, emphasizing the indications of psychotherapy if comorbidity is present. Psychotherapeutic care was carried out only among part of the population, because of parental reservations, exacerbated by differences of opinion among professionals and lack of access.

Conclusion

This study is innovative, providing precise data on ADHD from a multidisciplinary perspective. Psychopathological comorbidity is high in this population, so the concept of ADHD cannot be limited to a cognitive point of view. These elements and doubts regarding the efficacy of behavioural therapies suggest the need for a rigorous evaluation of analytical psychotherapies independent of MPH to treat attention deficit.     

Attention-deficit hyperactivity disorder (ADHD) and glial integrity: an exploration of associations of cytokines and kynurenine metabolites with symptoms and attention

Background  

In contrast to studies of depression and psychosis, the first part of this study showed no major differences in serum levels of cytokines and tryptophan metabolites between healthy children and those with attention-deficit/hyperactivity disorder of the combined type (ADHD). Yet, small decreases of potentially toxic kynurenine metabolites and increases of cytokines were evident in subgroups. Therefore we examined predictions of biochemical associations with the major symptom clusters, measures of attention and response variability.     

Migraine and associated comorbidities are three times more frequent in children with ADHD and their mothers

Objective

Attention deficit and hyperactivity disorder (ADHD) is a neuro-developmental disorder related to internalizing and externalizing disorders as well as somatic complaints and disorders. This study was conducted to evaluate the prevalence of headache subtypes, epilepsy, atopic disorders, motion sickness and recurrent abdominal pain among children and adolescents with ADHD and their parents.

Working memory deficits in adults with ADHD: is there evidence for subtype differences?

Background  

Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD). There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, however, remains to be more fully documented.     

Visual Perception of ADHD Children with Sensory Processing Disorder

Objective

The aim of the present study was to investigate the visual perception difference between ADHD children with and without sensory processing disorder, and the relationship between sensory processing and visual perception of the children with ADHD.

Methods

Participants were 47 outpatients, aged 6-8 years, diagnosed with ADHD. After excluding those who met exclusion criteria, 38 subjects were clustered into two groups, ADHD children with and without sensory processing disorder (SPD), using SSP reported by their parents, then subjects completed K-DTVP-2. Spearman correlation analysis was run to determine the relationship between sensory processing and visual perception, and Mann-Whitney-U test was conducted to compare the K-DTVP-2 score of two groups respectively.

Results

The ADHD children with SPD performed inferiorly to ADHD children without SPD in the on 3 quotients of K-DTVP-2. The GVP of K-DTVP-2 score was related to Movement Sensitivity section (r=0.368^*) and Low Energy/Weak section of SSP (r=0.369*).

Conclusion

The result of the present study suggests that among children with ADHD, the visual perception is lower in those children with co-morbid SPD. Also, visual perception may be related to sensory processing, especially in the reactions of vestibular and proprioceptive senses. Regarding academic performance, it is necessary to consider how sensory processing issues affect visual perception in children with ADHD.     

Attention deficit hyperactivity disorder in children is found to be related to the occurrence of ADHD in siblings and the male gender,but not to birth order,when compared to healthy controls

Objective. The aim of the present study was to explore the extent to which the prevalence of attention deficit hyperactivity disorder (ADHD) in childhood is associated with birth order and gender, and the prevalence of ADHD and mental retardation (MR) in siblings, as compared to healthy controls. Methods. Data from 200 children diagnosed with ADHD (mean age: 11.13 years; 10.5% females) were compared to data from 200 healthy controls (mean age: 11.0 years; 27.5% females). The data were related to symptoms of ADHD, birth order, gender, family size, and the occurrence of ADHD and MR in siblings. Results. Compared to controls, the occurrence of ADHD was found to be related to the male gender and to the occurrence of ADHD-related symptoms in siblings (odds ratio: 13.50). Birth order and MR were not associated with the occurrence of ADHD and ADHD-related symptoms. ADHD- related symptoms increased if a further sibling also suffered from ADHD. Conclusions. Among a sample of Iranian children suffering from ADHD, the ADHD and ADHD-related symptoms in childhood were found to be related to the male gender and to the occurrence of ADHD in siblings. Moreover, birth order was found to be unrelated. The fact that symptoms of ADHD-related symptoms increased if a further sibling was suffering from ADHD, and decreased if a further sibling was suffering from MR, is intriguing and needs further explanation.