Effect of psychostimulants on distinct attentional parameters in attentional deficit/hyperactivity disorder

Although there is extensive literature about the effects of stimulants on sustained attention tasks in attentional deficit/hyperactivity disorder (ADHD), little is known about the effect of these drugs on other attentional tasks involving different neural systems. In this study we measured the effect of stimulants on ADHD children, both in the electroencephalographic (EEG) activity during sustained attentional tasks and in psychometric performance during selective attentional tasks. These tasks are known to rely on different cortical networks. Our results in children medicated with 10 mg of d-amphetamine administered 60 min before the study indicate (i) a significant increase in amplitude but not latency of the P300 component of the event-related potential (ERP) during the sustained attentional task and (ii) a significant improvement in the reaction times and correct responses in the selective attentional task. In addition to supporting the use of stimulants in children with attentional deficit/hyperactivity disorder, these results show a multifocal activity improvement of cortical structures linked to dopamine, and interestingly, to attention. All these analyses are framed in a wider study of diverse attentional functions in this syndrome.     

Reflective and impulsive reactions in ADHD subtypes

Research on different subtypes of attention deficit hyperactivity disorder (ADHD) yielded inconsistent results regarding the nature of cognitive deficits. Whereas some studies report significant differences between subtypes, others fail to report these differences. In fact, the majority of studies in the field of ADHD does not differentiate between subtypes at all. The present study adopted the cognitive task of negating valence to compare the DSM-defined ADHD combined subtype (ADHD-C; n = 25), the inattentive subtype (ADHD-I; n = 25) and the control group (n = 30). As a main result, children with ADHD-C showed significant impairments compared to children with ADHD-I and the control group on conscious responses-driven by executive function, as well as on unconscious associative tasks. Medical treatment with stimulants positively influenced cognitive performance, although to a different extent for subgroups. The results are discussed in the context of current theories of ADHD and imply indications for further research in this field.     

Gap Effect Abnormalities during a Visually Guided Pro-Saccade Task in Children with Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that starts in early childhood and has a comprehensive impact on psychosocial activity and education as well as general health across the lifespan. Despite its prevalence, the current diagnostic criteria for ADHD are debated. Saccadic eye movements are easy to quantify and may be a quantitative biomarker for a wide variety of neurological and psychiatric disorders, including ADHD. The goal of this study was to examine whether children with ADHD exhibit abnormalities during a visually guided pro-saccadic eye-movement and to clarify the neurophysiological mechanisms associated with their behavioral impairments. Thirty-seven children with ADHD (aged 5–11 years) and 88 typically developing (TD) children (aged 5–11 years) were asked to perform a simple saccadic eye-movement task in which step and gap conditions were randomly interleaved. We evaluated the gap effect, which is the difference in the reaction time between the two conditions. Children with ADHD had a significantly longer reaction time than TD children (p < 0.01) and the gap effect was markedly attenuated (p < 0.01). These results suggest that the measurement of saccadic eye movements may provide a novel method for evaluating the behavioral symptoms and clinical features of ADHD, and that the gap effect is a potential biomarker for the diagnosis of ADHD in early childhood.     

Exercise impact on sustained attention of ADHD children, methylphenidate effects

Attention deficit hyperactivity disorder (ADHD) is related to a deficiency of central catecholamines (CA) in cognitive, biochemical, and physical tests, and pharmaceutical intervention may have no effect if it is not accompanied by changes in the environment. The objective of our study was to test the hypothesis that central CA are responsible for the increase in speed reaction seen after physical activity (PA) and to measure the impact of high intensity PA on the sustained attention of 25 children diagnosed with ADHD consistent with the Disease Statistical Mental-IV (DSM-IV) criteria. It is possible that practicing sports assists in the management of the disorder. The children were divided between users (US) and non-users (NUS) of methylphenidate (MTP), and the groups were compared to evaluate the effect of the drug on cognition after PA. Post-exercise performance on Conner's Continuous Performance Test-II (CPT) was not affected by MTP, we observed significant improvements in response time, and we saw normalization in the impulsivity and vigilance measures. These results suggest that the improvements in cognition after physical effort are not CA dependent. Additionally, our results suggest that children's attention deficits can be minimized through PA irrespective of treatment with MTP. Additional studies are necessary to confirm that exercise mitigates the harmful symptoms of ADHD.     

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。     

Electroencephalographic biofeedback of SMR and beta for treatment of attention deficit disorders in a clinical setting

Six children were provided with long-term biofeedback and academic treatment for attention deficit disorders. Their symptoms were primarily specific learning disabilities, and, in some cases, there were varying degrees of hyperkinesis. The training consisted of two sessions per week for 10 to 27 months, with a gradual phase-out. Feedback was provided for either increasing 12- to 15-Hz SMR or 16- to 20-Hz beta activity. Inhibit circuits were employed for blocking the SMR or beta when either gross movement, excessive EMG, or theta (4-8 Hz) activity was present. Treatment also consisted of combining the biofeedback with academic training, including reading, arithmetic, and spatial tasks to improve their attention. All children increased SMR or beta and decreased slow EEG and EMG activity. Changes could be seen in their power spectra after training in terms of increased beta and decreased slow activity. All six children demonstrated considerable improvement in their schoolwork in terms of grades or achievement test scores. None of the children are currently on any medications for hyperkinetic behavior. The results indicate that EEG biofeedback training, if applied comprehensively, can be highly effective in helping to remediate children who are experiencing attention deficit disorders.     

Characteristics of attention in children with attention deficit hyperactivity disorder (an analytical review)

The information concerning specific features of different attention components (alertness, sustention and selectivity) in children with attention deficit hyperactivity disorder (ADHD) is analyzed and systematized. According to the data reviewed, behavioral and attention problems described as ADHD are not homogeneous. Literature analysis of attention characteristics in children with ADHD shows that different components can be disrupted if ADHD is diagnosed as inattentive or combined subtype, but the main deficit in this case is that of selective voluntary attention. In case of hyperactivity/impulsivity subtype of ADHD, attention is impaired mainly in its brain activation components.     

Electroencephalographic biofeedback of SMR and beta for treatment of attention deficit disorders in a clinical setting

Six children were provided with long-term biofeedback and academic treatment for attention deficit disorders. Their symptoms were primarily specific learning disabilities, and, in some cases, there were varying degrees of hyperkinesis. The training consisted of two sessions per week for 10 to 27 months, with a gradual phase-out. Feedback was provided for either increasing 12-to 15-Hz SMR or 16- to 20-Hz beta activity. Inhibit circuits were employed for blocking the SMR or beta when either gross movement, excessive EMG, or theta (4–8 Hz) activity was present. Treatment also consisted of combining the biofeedback with academic training, including reading, arithmetic, and spatial tasks to improve their attention. All children increased SMR or beta and decreased slow EEG and EMG activity. Changes could be seen in their power spectra after training in terms of increased beta and decreased slow activity. All six children demonstrated considerable improvement in their schoolwork in terms of grades or achievement test scores. None of the children are currently on any medications for hyperkinetic behavior. The results indicate that EEG biofeedback training, if applied comprehensively, can be highly effective in helping to remediate children who are experiencing attention deficit disorders.The authors would like to thank Mr. Kevin Bianchini for his assistance in this study.     

Diagnosing and treating attention-deficit/hyperactivity disorder in adults

Adult attention deficit/hyperactivity disorder (ADHD) is a valid and impairing psychiatric disorder. In this article, we review the diagnosis of ADHD in adults, focusing on symptom presentation differences between pediatric and adult ADHD as well as the importance of assessing functional impairments. Differentiating ADHD from other clinical disorders is often the most difficult part of making an ADHD diagnosis in adults. Psychiatric comorbidities are also described and discussed as potential impact factors upon not only diagnosing ADHD but also treatment of adult ADHD. Especially in those adults with psychiatric comorbidities, treatments need to be multimodal and include both pharmacotherapy and psychosocial interventions.     

Fetal alcohol spectrum disorders among children in a Brazilian orphanage

Background: The objective was to investigate the frequency of fetal alcohol spectrum disorders (FASD) and ophthalmologic anomalies in orphanage children in Brazil. Methods: A prospective study was performed on 94 children living in an orphanage in Brazil. The children were examined by a multidisciplinary team consisting of specialists in pediatrics, neurology, psychology, neuropsychiatry, and ophthalmology. Results: The main reasons for living in the orphanage, in 61% of the children, were negligence, child abuse, and abandonment. Of all the children studied, 50% had mothers with known alcohol abuse and 47% had one or more diagnoses of neurodevelopmental/behavioral and/or cognitive deficits. General developmental delay was found in 18%, intellectual disability in 3%, cognitive impairment in 27%, attention‐deficit/hyperactivity disorder in 14%, and autism in 3%. Altogether 17% had FASD, comprising three children with fetal alcohol syndrome (FAS), six with partial FAS, and seven with alcohol‐related neurodevelopmental disorder. 16% had ophthalmological findings such as poor vision, strabismus, and dysmorphology of the optic nerves. Twenty‐eight children (30%) were adopted from the orphanage; of these, six had FASD (two FAS, three partial FAS, one alcohol‐related neurodevelopmental disorder), five had attention‐deficit/hyperactivity disorder, and eight had developmental delay. Conclusion: Nearly half of the children living in the orphanage had neurodevelopmental disorders and a considerable number showed signs of damage from prenatal alcohol exposure. A broader look at the problem of FASD in Brazil and other South American countries is desirable to document the burden of disease and provide data for targeting prevention efforts. Birth Defects Research (Part A) 103:178–185, 2015. © 2014 Wiley Periodicals, Inc.     

Effects of atomoxetine on attention in Wistar rats treated with the neurotoxin <Emphasis Type="Italic">N</Emphasis>-(2-chloroethyl)-<Emphasis Type="Italic">N</Emphasis>-ethyl-2-bromobenzylamine (DSP4)

The aim of the present study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), which allows a depletion of noradrenergic terminals in a dose-dependent manner, on attention in rats as measured using the five-choice serial-reaction time task (5CSRTT). In addition, we investigated whether the effects of DSP4 treatment can be reversed by atomoxetine. Atomoxetine is a selective noradrenaline reuptake inhibitor and has been shown to be effective in the treatment of attention deficit hyperactivity disorder. Wistar rats were trained in the 5CSRTT and treated with one of the three doses of DSP4 (10, 20 or 50 mg/kg) or saline. Following DSP4 treatment, rats were injected with three doses of atomoxetine (0.1, 0.5 or 1 mg/kg) or saline and tested in the 5CSRTT. The treatment with DSP4 caused a reduction in activity and a decline of performance in parameters related to attention in the 5CSRTT. Whether or not these impairments are due to attention deficits or changes in explorative behaviour and activity remains to be investigated. The treatment with atomoxetine had no beneficial effect on the rats’ performance regardless of the DSP4 treatment. The present findings support the role of noradrenaline in modulating attentional processes and call for future studies regarding the effects of atomoxetine on attention in rats.     

Early stress and chronic methylphenidate cross-sensitize dopaminergic responses in the adolescent medial prefrontal cortex and nucleus accumbens

Methylphenidate (MP) is widely used to treat attention deficit/hyperactivity disorder in children. However, basic research has been mainly focused on MP treatment in adult, behaviorally normal rodents. Here we analyzed MP-evoked changes of dopamine (DA) release in the limbic system of juvenile rodents with hyperactive and attention deficit-like symptoms. Using dual probe in vivo microdialysis, DA levels were quantified in the medial prefrontal cortex and nucleus accumbens of juvenile and adolescent degus ( Octodon degus ). Acute stress- and acute MP-evoked dopaminergic responses in normal juvenile and adolescent animals were compared with (i) animals showing symptoms of hyperactivity and attention deficits induced by early life stress, i.e. repeated parental separation during the first 3 weeks of life, and (ii) animals chronically treated with MP during pre-adolescence. Our main results revealed that (i) early life stress and (ii) chronic MP treatment during pre-adolescence cross-sensitize limbic dopaminergic functions in adolescent animals. Furthermore, we demonstrated a unique pattern of acute MP-evoked DA release in the juvenile compared with the adolescent medial prefrontal cortex and nucleus accumbens. Our findings that the functional maturation of dopaminergic limbic function is significantly altered by early life experience, i.e. repeated parental separation and chronic MP treatment, allow novel insights into the etiology of attention deficit/hyperactivity disorder and into the long-term consequences of MP treatment on brain development.     

EEG-Biocontrol Method in Treating the Attention Deficit Hyperactivity Disorder in Children

The problems of epidemiology, etiology, pathogenesis, and clinical signs of attention deficit hyperactivity disorder (ADHD) in children were considered. The literature review of the EEG-biocontrol method in treating ADHD in children, including the background, the theoretical basis of the method, and the assessment of its effectiveness, is presented. Specific features of the EEG-biocontrol protocols based on the data of different authors are given. The comparative assessment of the efficacy of EEG-biocontrol and drug treatment with the use of psychostimulants in ADHD is presented.     

Functional deficits in basal ganglia of children with attention-deficit/hyperactivity disorder shown with functional magnetic resonance imaging relaxometry

Attention-deficit/hyperactivity disorder is a highly heritable and prevalent neuropsychiatric disorder estimated to affect 6% of school-age children. Its clinical hallmarks are inattention, hyperactivity and impulsivity, which often respond substantially to treatment with methylphenidate or dextroamphetamine. Etiological theories suggest a deficit in corticostriatal circuits, particularly those components modulated by dopamine. We developed a new functional magnetic resonance imaging procedure (T2 relaxometry) to indirectly assess blood volume in the striatum (caudate and putamen) of boys 6-12 years of age in steady-state conditions. Boys with attention-deficit/hyperactivity disorder had higher T2 relaxation time measures in the putamen bilaterally than healthy control subjects. Relaxation times strongly correlated with the child's capacity to sit still and his accuracy in accomplishing a computerized attention task. Daily treatment with methylphenidate significantly changed the T2 relaxation times in the putamen of children with attention-deficit/hyperactivity disorder, although the magnitude and direction of the effect was strongly dependent on the child's unmedicated activity state. There was a similar but nonsignificant trend in the right caudate. T2 relaxation time measures in thalamus did not differ significantly between groups, and were not affected by methylphenidate. Attention-deficit/hyperactivity disorder symptoms may be closely tied to functional abnormalities in the putamen, which is mainly involved in the regulation of motor behavior.     

Increased oxidative stress in children with attention deficit hyperactivity disorder

Objectives: The purpose of this study was to investigate oxidative stress in children with attention deficit hyperactivity disorder (ADHD).

Methods: Total oxidant status (TOS), total antioxidant status (TAS), paraxonase-1 (PON-1) and arylesterase (ARE) activity were measured in 76 children (44 boys, 32 girls) diagnosed with ADHD according to the DSM-IV and 78 healthy children (46 boys, 32 girls).

Results: Age and sex were similar between the groups (P?>?0.05). TOS and the oxidative stress index (OSI) were higher in the patient group than the control group (P?<?0.001). PON-1 (P?=?0.002), ARE (P?=?0.010) activity and TAS (P?<?0.001) were lower in the patient group than the control group.

Discussion: We found decreased PON-1, ARE activity and TAS, and increased TOS and OSI in children with ADHD. Our study showed that there is significantly increased oxidative stress in children with ADHD.     

Linguistic Analysis of the Preschool Five Minute Speech Sample: What the Parents of Preschool Children with Early Signs of ADHD Say and How They Say It?

A linguistic analysis was performed on the Preschool Five Minute Speech Sample (PFMSS) of 42 parents. PFMSS is a validated measure for Expressed Emotion (EE) to assess parent-child relationship. Half of these parents (n = 21, clinical group) had preschool children with early symptoms of attention deficit hyperactivity disorder (ADHD), the rest had typically developing children. Early symptoms of ADHD were identified with the Werry-Weiss Peters Rating Scale. The linguistic component of the PFMSS was analysed with keyword and linguistic pattern identification. The results of these two complementary analyses (i.e., EE and linguistic analysis) provided relevant recommendations that may improve the efficacy of psychological treatment for ADHD such as parenting interventions. We discuss the practical implications of these findings.     

Methylphenidate is not clastogenic in cultured human lymphocytes and in the mouse bone-marrow micronucleus test

Methylphenidate (MPH) is one of the most frequently prescribed drugs for the treatment of attention deficit hyperactivity disorder (ADHD). A report on cytogenetic effects observed in peripheral lymphocytes from children treated for 3 months with MPH raised questions about the genetic toxicity of this compound. A critical review of this data concluded that the cytogenetic effects in treated children remain unexplained. A literature review showed that MPH was found negative in most genetox studies performed, but no in vitro chromosome aberration data in human lymphocytes have been published. Therefore, we conducted a chromosomal aberration study in cultured human peripheral lymphocytes. The results of this investigation showed that d,l-methylphenidate (MPH, Ritalin) in concentrations up to 10 mM did neither induce structural nor numerical chromosome abnormalities. An oral mouse bone-marrow micronucleus test in B6C3F(1) mice, with doses up to 250 mg/kg bw, was negative too. The data of these studies confirm the absence of clastogenic activity of MPH in non-clinical studies.     

The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1

Neurofibromatosis Type 1 (NF1) is a common neurological disorder caused by mutations in the gene encoding Neurofibromin, a p21Ras GTPase Activating Protein (GAP). Importantly, NF1 causes learning disabilities and attention deficits. A previous study showed that the learning and memory deficits of a mouse model of NF1 (nf1+/-) appear to be caused by excessive p21Ras activity leading to impairments in long-term potentiation (LTP), a cellular mechanism of learning and memory. Here, we identify lovastatin as a potent inhibitor of p21Ras/Mitogen Activated Protein Kinase (MAPK) activity in the brain. Lovastatin is a specific inhibitor of three-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, used commonly for the treatment of hypercholesterolemia. We report that lovastatin decreased the enhanced brain p21Ras-MAPK activity of the nf1+/- mice, rescued their LTP deficits, and reversed their spatial learning and attention impairments. Therefore, these results demonstrate that lovastatin may prove useful in the treatment of Neurofibromatosis Type 1.     

Evaluation of oxidative stress status in children with pervasive developmental disorder and attention deficit hyperactivity disorder using urinary-specific biomarkers

Pervasive developmental disorder (PDD) and attention deficit hyperactivity disorder (ADHD) are likely to be associated with increased oxidative stress, particularly that of lipid peroxidation. We evaluated the oxidative stress status of pediatric PDD and ADHD patients using their urine samples. Urinary acrolein-lysine levels in 11 PDD and 10 ADHD children (205 ± 97 and 234 ± 75 nmol/mg Cr, respectively) appeared higher than those of the control subjects (155 ± 59 nmol/mg Cr). Measurement of urinary specific biomarkers is comfortable, non-invasive, and easy to perform in children. Our findings might provide a scientific guide for use in further clinical and biochemical studies of these disorders.