Protopathic stimulant use among children with symptoms of ADHD

The purpose of the current study was to examine protopathic stimulant use among children with the symptoms of ADHD but do not have a diagnosis of ADHD. Protopathic or prodromal stimulant use refers to the use of stimulants by children with the symptoms of ADHD prior to a diagnosis of ADHD. In the current study, we examined children with the symptoms of ADHD who received stimulant treatment across time and with respect to several background variables. Our results indicate that these children who receive stimulant treatment without a diagnosis of ADHD are significantly more like to be eventually diagnosed with ADHD than not. Results also indicate that these children who receive stimulant treatment but do not yet have a diagnosis of ADHD are significantly more likely to have insurance that does not pay for diagnostic procedures. These results are discussed in view of treatment.     

Cost-Effectiveness of Extended-Release Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder Sub-Optimally Treated with Immediate Release Methylphenidate

BackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH) is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at school often leads to reduced compliance, sub-optimal treatment, and therefore economic loss. Replacement of IR-MPH with a single-dose extended release (ER-MPH) formulation may improve drug response and economic efficiency.ObjectiveTo evaluate the cost-effectiveness from a societal perspective of a switch from IR-MPH to ER-MPH in patients who are sub-optimally treated.MethodsA daily Markov-cycle model covering a time-span of 10 years was developed including four different health states: (1) optimal response, (2) sub-optimal response, (3) discontinued treatment, and (4) natural remission. ER-MPH options included methylphenidate osmotic release oral system (MPH-OROS) and Equasym XL/Medikinet CR. Both direct costs and indirect costs were included in the analysis, and effects were expressed as quality-adjusted life years (QALYs). Univariate, multivariate as well as probabilistic sensitivity analysis were conducted and the main outcomes were incremental cost-effectiveness ratios.ResultsSwitching sub-optimally treated patients from IR-MPH to MPH-OROS or Equasym XL/Medikinet CR led to per-patient cost-savings of €4200 and €5400, respectively, over a 10-year treatment span. Sensitivity analysis with plausible variations of input parameters resulted in cost-savings in the vast majority of estimations.ConclusionsThis study lends economic support to switching patients with ADHD with suboptimal response to short-acting IR-MPH to long-acting ER-MPH regimens.     

Increased fractional anisotropy in white matter of the right frontal region in children with attention-deficit/hyperactivity disorder: a diffusion tensor imaging study

Abnormalities of frontal white matter (WM) have been found in some children with ADHD. The purpose of this study was to explore the changes in WM in child patients with ADHD by DTI, which detects changes in WM microstructure based on properties of diffusion. We also expect to investigate the relationship between the changes in WM and executive function in child patients with ADHD. DTI was performed on 24 patients with ADHD and 20 healthy controls. A series of neuropsychological tests and a structural interview were conducted to assess the cognitive functions and clinical data of the ADHD patients and controls. Firstly, child patients with ADHD have higher fractional anisotropy (FA) values in WM in the right frontal region. Secondly, FA in right frontal WM is positively correlated with scores in the Stroop test. CONCLUSIONS: Increased FA of right frontal WM implies a higher degree of myelination and lower degree of neural branching in WM, contributing to the neurological deficits of ADHD.     

Training of attention functions in children with attention deficit hyperactivity disorder

Pharmacological treatment of children with ADHD has been shown to be successful; however, medication may not normalize attention functions. The present study was based on a neuropsychological model of attention and assessed the effect of an attention training program on attentional functioning of children with ADHD. Thirty-two children with ADHD and 16 healthy children participated in the study. Children with ADHD were randomly assigned to one of the two conditions, i.e., an attention training program which trained aspects of vigilance, selective attention and divided attention, or a visual perception training which trained perceptual skills, such as perception of figure and ground, form constancy and position in space. The training programs were applied in individual sessions, twice a week, for a period of four consecutive weeks. Healthy children did not receive any training. Alertness, vigilance, selective attention, divided attention, and flexibility were examined prior to and following the interventions. Children with ADHD were assessed and trained while on ADHD medications. Data analysis revealed that the attention training used in the present study led to significant improvements of various aspects of attention, including vigilance, divided attention, and flexibility, while the visual perception training had no specific effects. The findings indicate that attention training programs have the potential to facilitate attentional functioning in children with ADHD treated with ADHD drugs.     

Effect of polyphenolic extract, Pycnogenol, on the level of 8-oxoguanine in children suffering from attention deficit/hyperactivity disorder

The purpose of this randomized, double-blind and placebo controlled study was to test the effect of polyphenolic extract of pine bark Pycnogenol^® (Pyc) on the level of oxidized purines represented by 8-oxo-7,8-dihydroguanine (8-oxoG) and on the total antioxidant status (TAS) in children with attention deficit/hyperactivity disorder (ADHD).

We have found significantly increased damage to DNA in ADHD children when compared to controls. 8-oxoG was significantly lower after 1 month of Pyc administration in comparison to the beginning state and to placebo group. TAS in ADHD children was lower in comparison to controls. After Pyc administration, TAS was elevated but statistically significant increase was recorded after 1 month of termination of Pyc application. Improvement of DNA damage and TAS after Pyc administration is associated with the improvement of attention in ADHD children.

In conclusion, Pycnogenol^® administration reduces oxidative damage to DNA, normalizes TAS and improves attention of ADHD children. Explanation of mutual relation between oxidative damage to DNA, TAS and symptoms of ADHD and mechanism of Pyc's action needs further investigations.     

Detection of malingered attention deficit hyperactivity disorder

The aim of the present study was to determine whether malingering of adult attention deficit hyperactivity disorder (ADHD) can be detected using a self-report rating scale. A sample of 78 university students was allocated to three different conditions. The conditions were (a) a control group, (b) a na?ve simulation group and (c) a coached simulation group. Furthermore, 12 adult students with a diagnosed ADHD participated in the present study. Participants were administered the Brown Attention Deficit Disorder Scale for Adults. While the control group and the patient group were asked to complete the scale with accuracy, the simulation groups were requested to feign an ADHD. Statistical analysis revealed that both simulation groups were able to successfully feign an ADHD. The results indicate that self-report rating measures are not sensitive enough to allow the detection of feigned ADHD.     

Olfactory and gustatory sensitivity in adults with attention-deficit/hyperactivity disorder

Recently, research on olfactory functions in attention-deficit/hyperactivity disorder (ADHD) has become prominent, whereas gustation has never been investigated. Increased odor sensitivity was found in medication-na?ve children with ADHD, but not in adult ADHD, which might be due to a dopaminergic dysregulation presumed to underlie this disorder. Taste sensitivity, in particular bitter sensitivity as a hereditary trait, also might be altered in ADHD. To examine olfactory and gustatory functions in adult ADHD patients, we assessed odor sensitivity by Sniffin' Sticks, taste sensitivity by taste strips, and bitter sensitivity by the one-solution test in women with ADHD (n = 12), Bulimia Nervosa (n = 12), and healthy control women (n = 12). Bulimia Nervosa as second patient group was included to control for effects of impulsivity. Preliminary results indicate that ADHD patients were significantly more often classified as tasters, i.e. perceived the bitter taste as more intense, compared to both bulimic patients and healthy controls. No group differences were found with regard to general odor and taste sensitivity. It is proposed that the higher frequency of tasters in ADHD patients might underlie a genetic variation of the bitter receptor-dependent signaling pathway associated with ADHD.     

Individual responses to methylphenidate and caffeine in children with minimal brain dysfunction.

Eight children with minimal brain dysfunction were studied for their individual responses to two stimulant medications--methylphenidate hydrochloride and caffeine citrate. Four types of behavioural responses were observed in the double-blind crossover experiment: four children responded favourably to both psychostimulants, one responded to methylphenidate alone and two responded to the placebo. The behaviour of one child deteriorated while he was taking methylphenidate and caffeine. In general, methylphenidate was superior to caffeine in diminishing hyperactive and aggressive behaviour. It is apparent that such stimulant medication exerts its therapeutic effects in these two areas primarily and would therefore be useful as one aspect of a complete treatment program for children with this syndrome.     

Laminar Thickness Alterations in the Fronto-Parietal Cortical Mantle of Patients with Attention-Deficit/Hyperactivity Disorder

Although Attention-Deficit/Hyperactivity Disorder (ADHD) was initially regarded as a disorder exclusive to childhood, nowadays its prevalence in adulthood is well established. The development of novel techniques for quantifying the thickness of the cerebral mantle allows the further exploration of the neuroanatomical profiles underlying the child and adult form of the disorder. To examine the cortical mantle in children and adults with ADHD, we applied a vertex-wise analysis of cortical thickness to anatomical brain MRI scans acquired from children with (n = 43) and without ADHD (n = 41), as well as a group of adult neurotypical individuals (n = 31), adult patients with a history of stimulant treatment (n = 31) and medication-naïve adults with ADHD (n = 24). We observed several clusters of reduced laminar cortical thickness in ADHD patients in comparison to neurotypical individuals. These differences were primarily located in the dorsal attention network, including the bilateral inferior and superior parietal cortex and a section of the frontal cortex (centered on the superior frontal and precentral gyrus bilaterally). Further laminar thickness deficits were observed in the bilateral orbitofrontal cortex and medial occipital cortex. The deficits in the cortical surface were especially pronounced in the child sample, while adult patients showed a more typical laminar thickness across the cerebral mantle. These findings show that the neuroanatomical profile of ADHD, especially the childhood form of the disorder, involves robust alterations in the cortical mantle, which are most prominent in brain regions subserving attentional processing.     

Neurocognitive training for children with and without AD/HD

There is accumulating evidence that computerised cognitive training of inhibitory control and/or working memory can lead to behavioural improvement in children with AD/HD. Using a randomised waitlist control design, the present study examined the effects of combined working memory and inhibitory control training, with and without passive attention monitoring via EEG, for children with and without AD/HD. One hundred and twenty-eight children (60 children with AD/HD, 68 without AD/HD) were randomly allocated to one of three training conditions (waitlist; working memory and inhibitory control with attention monitoring; working memory and inhibitory control without attention monitoring) and completed with pre- and post-training assessments of overt behaviour (from 2 sources), trained and untrained cognitive task performance, and resting EEG activity. The two active training conditions completed 25 sessions of training at home over a 4- 5-week period. Results showed significant improvements in overt behaviour for children with AD/HD in both training conditions compared to the waitlist condition as rated by a parent and other adult. Post-training improvements in the areas of spatial working memory, ignoring distracting stimuli, and sustained attention were reported for children with AD/HD. Children without AD/HD showed behavioural improvements after training. The improvements for both groups were maintained over the 6-week period following training. The passive attention monitoring via EEG had a minor effect on training outcomes. Overall, the results suggest that combined WM/IC training can result in improved behavioural control for children with and without AD/HD.     

Neurofeedback for Children with ADHD: A Comparison of SCP and Theta/Beta Protocols

Behavioral and cognitive improvements in children with ADHD have been consistently reported after neurofeedback-treatment. However, neurofeedback has not been commonly accepted as a treatment for ADHD. This study addresses previous methodological shortcomings while comparing a neurofeedback-training of Theta-Beta frequencies and training of slow cortical potentials (SCPs). The study aimed at answering (a) whether patients were able to demonstrate learning of cortical self-regulation, (b) if treatment leads to an improvement in cognition and behavior and (c) if the two experimental groups differ in cognitive and behavioral outcome variables. SCP participants were trained to produce positive and negative SCP-shifts while the Theta/Beta participants were trained to suppress Theta (4–8 Hz) while increasing Beta (12–20 Hz). Participants were blind to group assignment. Assessment included potentially confounding variables. Each group was comprised of 19 children with ADHD (aged 8–13 years). The treatment procedure consisted of three phases of 10 sessions each. Both groups were able to intentionally regulate cortical activity and improved in attention and IQ. Parents and teachers reported significant behavioral and cognitive improvements. Clinical effects for both groups remained stable six months after treatment. Groups did not differ in behavioural or cognitive outcome.     

Horizontal transmission of epizootic ulcerative syndrome (EUS)-associated virus in the snakehead Ophicephalus striatus under simulated natural conditions

Natural transmission of the epizootic ulcerative syndrome (EUS) was conducted on na?ve snakeheads Ophicephalus striatus (also known as Channa striata) kept (A) in aquifer water, (B) in lakewater, (C) cohabiting with EUS snakeheads in lakewater, and (D) cohabiting with apparently healthy snakeheads in lakewater during the 1994 to 1995 EUS season. The results showed that EUS-like lesions developed in 6 to 14 d among na?ve snakeheads cohabiting with EUS snakeheads and with apparently healthy snakeheads in lakewater (Treatments C and D). Among na?ve fish exposed to lakewater (Treatment B), similar lesions developed in 16 to 21 d, while na?ve fish in aquifer water (Treatment A) did not develop EUS-like lesions. EUS signs began as Grade I (slight) lesions that gradually progressed to Grades III-IV (severe) 3 to 5 d from lesion onset, similar to the naturally affected EUS fish. The virus was recovered from some but not all naturally EUS-affected snakeheads, snakeheads with healing lesions and apparently healthy snakeheads, but not from na?ve snakeheads. The results provide evidence of a waterborne horizontal transmission of the EUS-associated virus. This is the first report of a successful horizontal transmission of the EUS-associated virus from apparently healthy snakeheads to na?ve fish under natural conditions and of virus recovery in tissue culture from naturally exposed experimental fish.     

Psychoeducational groups for youth attention-deficit hyperactivity disorder: a family medicine pilot project

Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed behavioural disorder of youth and is estimated to affect ～4% of school-age children. Although medication is the most common and efficacious treatment for ADHD, some experts believe that multimodal treatment strategies help children improve symptoms more than medicine alone. Psychoeducational strategies focus on educating youth and families about a given disorder. This study compared youth who participated with their parents in a five-session, one-hour psychoeducational group at a family medicine clinic and those who received customary treatment and were on a waiting list for the intervention. Findings of youth behaviour from parent and teacher perspectives were compared at the outset of the group and one month after group completion using the Vanderbilt scales. Results revealed that youth in both conditions improved over the two months of the study from the parent perspective in terms of all ADHD symptoms (e.g. inattention, hyperactivity/impulsivity) and in terms of school functioning. However, no gains were made in youth functioning or ADHD behaviour from the teacher perspective. Youth in the treatment group made modest gains in school performance from the parent perspective when compared with youth in the control condition. The results suggest that parents of ADHD youth should be involved in the treatment process to maximise the likelihood of improvement. Psychoeducational groups can be of modest benefit to help educate parents and youth regarding the challenges of ADHD management.     

Lymphoid tissue damage in HIV-1 infection depletes naïve T cells and limits T cell reconstitution after antiretroviral therapy

Highly active antiretroviral therapy (HAART) can suppress HIV-1 replication and normalize the chronic immune activation associated with infection, but restoration of na?ve CD4+ T cell populations is slow and usually incomplete for reasons that have yet to be determined. We tested the hypothesis that damage to the lymphoid tissue (LT) fibroblastic reticular cell (FRC) network contributes to na?ve T cell loss in HIV-1 infection by restricting access to critical factors required for T cell survival. We show that collagen deposition and progressive loss of the FRC network in LTs prior to treatment restrict both access to and a major source of the survival factor interleukin-7 (IL-7). As a consequence, apoptosis within na?ve T cell populations increases significantly, resulting in progressive depletion of both na?ve CD4+ and CD8+ T cell populations. We further show that the extent of loss of the FRC network and collagen deposition predict the extent of restoration of the na?ve T cell population after 6 month of HAART, and that restoration of FRC networks correlates with the stage of disease at which the therapy is initiated. Because restoration of the FRC network and reconstitution of na?ve T cell populations are only optimal when therapy is initiated in the early/acute stage of infection, our findings strongly suggest that HAART should be initiated as soon as possible. Moreover, our findings also point to the potential use of adjunctive anti-fibrotic therapies to avert or moderate the pathological consequences of LT fibrosis, thereby improving immune reconstitution.     

Attention-deficit hyperactive disorder presenting with school truancy in an adolescent: a case report

Attention-deficit hyperactive disorder (ADHD) is a psychiatric illness commonly diagnosed during the early years of childhood. In many adolescents with undiagnosed ADHD, presentation may not be entirely similar to that in younger children. These adolescents pose significant challenges to parents and teachers coping with their disability. Often adolescents with behavioural problems are brought to medical attention as a last resort. This case describes an adolescent who presented to a primary care clinic with school truancy. He was initially treated for depression with oppositional defiant disorder and sibling rivalry. Only following a careful detailed history and further investigations was the diagnosis of ADHD made. He showed a positive improvement with the use of methylphenidate for his ADHD and escitalopram for his depression. The success of his management was further supported by the use of behavioural therapy and parenting interventions. There is a need to increase public awareness of ADHD, especially among parents and teachers so that early intervention can be instituted in these children.     

A pilot study of combined working memory and inhibition training for children with AD/HD

Building on recent favourable outcomes using working memory (WM) training, this study examined the behavioural and physiological effect of concurrent computer-based WM and inhibition training for children with attention-deficit hyperactivity disorder (AD/HD). Using a double-blind active-control design, 29 children with AD/HD completed a 5-week at-home training programme and pre- and post-training sessions which included the assessment of overt behaviour, resting EEG, as well as task performance, skin conductance level and event-related potentials (ERPs) during a Go/Nogo task. Results indicated that after training, children from the high-intensity training condition showed reduced frequency of inattention and hyperactivity symptoms. Although there were trends for improved Go/Nogo performance, increased arousal and specific training effects for the inhibition-related N2 ERP component, they failed to reach standard levels of statistical significance. Both the low- and high-intensity conditions showed resting EEG changes (increased delta, reduced alpha and theta activity) and improved early attention alerting to Go and Nogo stimuli, as indicated by the N1 ERP component, post-training. Despite limitations, this preliminary work indicates the potential for cognitive training that concurrently targets the interrelated processes of WM and inhibition to be used as a treatment for AD/HD.     

Working Memory-Related Functional Brain Patterns in Never Medicated Children with ADHD

Attention Deficit/Hyperactivity Disorder (ADHD) is a pervasive neurodevelopmental disorder characterized by 3 clusters of age-inappropriate cardinal symptoms: inattention, hyperactivity and impulsivity. These clinical/behavioural symptoms are assumed to result from disturbances within brain systems supporting executive functions including working memory (WM), which refers to the ability to transiently store and flexibly manipulate task-relevant information. Ongoing or past medications, co-morbidity and differences in task performance are potential, independent confounds in assessing the integrity of cerebral patterns in ADHD. In the present study, we recorded WM-related cerebral activity during a memory updating N-back task using functional Magnetic Resonance Imaging (fMRI) in control children and never medicated, prepubescent children with ADHD but without comorbid symptoms. Despite similar updating performance than controls, children with ADHD exhibited decreased, below baseline WM-related activation levels in a widespread cortico-subcortical network encompassing bilateral occipital and inferior parietal areas, caudate nucleus, cerebellum and functionally connected brainstem nuclei. Distinctive functional connectivity patterns were also found in the ADHD in these regions, with a tighter coupling in the updating than in the control condition with a distributed WM-related cerebral network. Especially, cerebellum showed tighter coupling with activity in an area compatible with the brainstem red nucleus. These results in children with clinical core symptoms of ADHD but without comorbid affections and never treated with medication yield evidence for a core functional neuroanatomical network subtending WM-related processes in ADHD, which may participate to the pathophysiology and expression of clinical symptoms.     

脑电生物反馈训练对ADHD 儿童心理、行为的影响

目的：探讨脑电生物反馈治疗对ADHD儿童心理、行为的影响。方法：对45例ADHD儿童采用脑电生物反馈训练。20次为一个疗程。治疗前和治疗后20、40次分别用症状评定量表进行比较。结果：接受20次训练的ADHD儿童注意、情感、活动水平、异常行为、学业等方面的问题都有明显好转;接受40次训练的ADHD儿童注意、情感、活动水平、异常行为、学业等方面的问题改善十分明显。P值〈0.01差异显著。结论：脑电生物反馈训练能有效地改善儿童注意、情感、活动水平、异常行为、学业等方面的问题。     

Multimodal Magnetic Resonance Imaging Study of Treatment-Na?ve Adults with Attention-Deficit/Hyperactivity Disorder

Background

Attention-Deficit/Hiperactivity Disorder (ADHD) is a prevalent disorder, but its neuroanatomical circuitry is still relatively understudied, especially in the adult population. The few morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies available to date have found heterogeneous results. This may be at least partly attributable to some well-known technical limitations of the conventional voxel-based methods usually employed to analyze such neuroimaging data. Moreover, there is a great paucity of imaging studies of adult ADHD to date that have excluded patients with history of use of stimulant medication.

Methods

A newly validated method named optimally-discriminative voxel-based analysis (ODVBA) was applied to multimodal (structural and DTI) MRI data acquired from 22 treatment-naïve ADHD adults and 19 age- and gender-matched healthy controls (HC).

Results

Regarding DTI data, we found higher fractional anisotropy in ADHD relative to HC encompassing the white matter (WM) of the bilateral superior frontal gyrus, right middle frontal left gyrus, left postcentral gyrus, bilateral cingulate gyrus, bilateral middle temporal gyrus and right superior temporal gyrus; reductions in trace (a measure of diffusivity) in ADHD relative to HC were also found in fronto-striatal-parieto-occipital circuits, including the right superior frontal gyrus and bilateral middle frontal gyrus, right precentral gyrus, left middle occipital gyrus and bilateral cingulate gyrus, as well as the left body and right splenium of the corpus callosum, right superior corona radiata, and right superior longitudinal and fronto-occipital fasciculi. Volumetric abnormalities in ADHD subjects were found only at a trend level of significance, including reduced gray matter (GM) in the right angular gyrus, and increased GM in the right supplementary motor area and superior frontal gyrus.

Conclusions

Our results suggest that adult ADHD is associated with neuroanatomical abnormalities mainly affecting the WM microstructure in fronto-parieto-temporal circuits that have been implicated in cognitive, emotional and visuomotor processes.