Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD

Impulsivity and hyperactivity are two facets of attention deficit/hyperactivity disorder (ADHD). Impulsivity is expressed as reduced response inhibition capacity, an executive control mechanism that prevents premature execution of an intermittently reinforced behavior. During methylphenidate treatment, impulsivity and hyperactivity are decreased in adolescents with ADHD, but there is little information concerning levels of impulsivity and hyperactivity in adulthood after adolescent methylphenidate treatment is discontinued. The current study evaluated impulsivity, hyperactivity as well as cocaine sensitization during adulthood after adolescent methylphenidate treatment was discontinued in the Spontaneously Hypertensive Rat (SHR) model of ADHD. Treatments consisted of oral methylphenidate (1.5mg/kg) or water vehicle provided Monday-Friday from postnatal days 28-55. During adulthood, impulsivity was measured in SHR and control strains (Wistar Kyoto and Wistar rats) using differential reinforcement of low rate (DRL) schedules. Locomotor activity and cocaine sensitization were measured using the open-field assay. Adult SHR exhibited decreased efficiency of reinforcement under the DRL30 schedule and greater levels of locomotor activity and cocaine sensitization compared to control strains. Compared to vehicle, methylphenidate treatment during adolescence reduced hyperactivity in adult SHR, maintained the lower efficiency of reinforcement, and increased burst responding under DRL30. Cocaine sensitization was not altered following adolescent methylphenidate in adult SHR. In conclusion, adolescent treatment with methylphenidate followed by discontinuation in adulthood had a positive benefit by reducing hyperactivity in adult SHR rats; however, increased burst responding under DRL compared to SHR given vehicle, i.e., elevated impulsivity, constituted an adverse consequence associated with increased risk for cocaine abuse liability.P50 DA005312 - NIDA NIH HHS; R01 DA011716 - NIDA NIH HHS; P50 DA05312 - NIDA NIH HH

Dampening Spontaneous Activity Improves the Light Sensitivity and Spatial Acuity of Optogenetic Retinal Prosthetic Responses

Retinitis pigmentosa is a progressive retinal dystrophy that causes irreversible visual impairment and blindness. Retinal prostheses currently represent the only clinically available vision-restoring treatment, but the quality of vision returned remains poor. Recently, it has been suggested that the pathological spontaneous hyperactivity present in dystrophic retinas may contribute to the poor quality of vision returned by retinal prosthetics by reducing the signal-to-noise ratio of prosthetic responses. Here, we investigated to what extent blocking this hyperactivity can improve optogenetic retinal prosthetic responses. We recorded activity from channelrhodopsin-expressing retinal ganglion cells in retinal wholemounts in a mouse model of retinitis pigmentosa. Sophisticated stimuli, inspired by those used in clinical visual assessment, were used to assess light sensitivity, contrast sensitivity and spatial acuity of optogenetic responses; in all cases these were improved after blocking spontaneous hyperactivity using meclofenamic acid, a gap junction blocker. Our results suggest that this approach significantly improves the quality of vision returned by retinal prosthetics, paving the way to novel clinical applications. Moreover, the improvements in sensitivity achieved by blocking spontaneous hyperactivity may extend the dynamic range of optogenetic retinal prostheses, allowing them to be used at lower light intensities such as those encountered in everyday life

From clinical application to cognitive enhancement: the example of methylphenidate

Methylphenidate (MPD) is a central nervous system (CNS) stimulant, which belongs to the phenethylamine group and is mainly used in the treatment of attention deficit hyperactive disorder (ADHD). However, a growing number of young individuals misuse or abuse MPD to sustain attention, enhance intellectual capacity and increase memory. Recently, the use of MPD as a cognitive enhancement substance has received much attention and raised concerns in the literature and academic circles worldwide. The prescribing frequency of the drug has increased sharply asconsequence of the more accurate diagnosis of the ADHD and the popularity of the drug itself due to its beneficial short-term effect. However, careful monitoring is required, because of possible abuse. In this review different aspects concerning the use of MPD have been approached. Data showing its abuse among college students are given, when the drug is prescribed short term beneficial effects and side effects are provided; moreover studies on animal-models suggesting long lasting negative effects on healthy brains are discussed. Finally, emphasis is given to the available formulationsand pharmacology

Familial influences on the full range of variability in attention and activity levels during adolescence: A longitudinal twin study

AbstractTo investigate familial influences on the full range of variability in attention and activity across adolescence, we collected maternal ratings of 339 twin pairs at ages 12, 14, and 16, and estimated the transmitted and new familial influences on attention and activity as measured by the Strengths and Weaknesses of Attention-Deficit/Hyperactivity Disorder Symptoms and Normal Behavior Scale. Familial influences were substantial for both traits across adolescence: genetic influences accounted for 54%–73% (attention) and 31%–73% (activity) of the total variance, and shared environmental influences accounted for 0%–22% of the attention variance and 13%–57% of the activity variance. The longitudinal stability of individual differences in attention and activity was largely accounted for by familial influences transmitted from previous ages. Innovations over adolescence were also partially attributable to familial influences. Studying the full range of variability in attention and activity may facilitate our understanding of attention-deficit/hyperactivity disorder's etiology and intervention.</jats:p

A review of the economic burden of ADHD

Attention-deficit hyperactivity disorder (ADHD) is a common disorder that is associated with broad functional impairment among both children and adults. The purpose of this paper is to review and summarize available literature on the economic costs of ADHD, as well as potential economic benefits of treating this condition. A literature search was performed using MEDLINE to identify all published articles on the economic implications of ADHD, and authors were contacted to locate conference abstracts and articles in press that were not yet indexed. In total, 22 relevant items were located including published original studies, economic review articles, conference presentations, and reports available on the Internet. All costs were updated and presented in terms of year 2004 US dollars. A growing body of literature, primarily published in the United States, has demonstrated that ADHD places a substantial economic burden on patients, families, and third-party payers. Results of the medical cost studies consistently indicated that children with ADHD had higher annual medical costs than either matched controls (difference ranged from $503 to$1,343) or non-matched controls (difference ranged from $207 to$1,560) without ADHD. Two studies of adult samples found similar results, with significantly higher annual medical costs among adults with ADHD (ranging from $4,929 to$5,651) than among matched controls (ranging from $1,473 to$2,771). A limited number of studies have examined other economic implications of ADHD including costs to families; costs of criminality among individuals with ADHD; costs related to common psychiatric and medical comorbidities of ADHD; indirect costs associated with work loss among adults with ADHD; and costs of accidents among individuals with ADHD. Treatment cost-effectiveness studies have primarily focused on methylphenidate, which is a cost-effective treatment option with cost-effectiveness ratios ranging from $15,509 to$27,766 per quality-adjusted life year (QALY) gained. As new treatments are introduced it will be important to evaluate their cost-effectiveness to provide an indication of their potential value to clinicians, patients, families, and third-party payers

Which executive functioning deficits are associated with AD/HD, ODD/CD and comorbid AD/HD+ODD/CD?

Item does not contain fulltextThis study investigated (1) whether attention deficit/hyperactivity disorder (AD/HD) is associated with executive functioning (EF) deficits while controlling for oppositional defiant disorder/conduct disorder (ODD/CD), (2) whether ODD/CD is associated with EF deficits while controlling for AD/HD, and (3)~whether a combination of AD/HD and ODD/CD is associated with EF deficits (and the possibility that there is no association between EF deficits and AD/HD or ODD/CD in isolation). Subjects were 99~children ages 6–12 years. Three putative domains of EF were investigated using well-validated tests: verbal fluency, working memory, and planning. Independent of ODD/CD, AD/HD was associated with deficits in planning and working memory, but not in verbal fluency. Only teacher rated AD/HD, but not parent rated AD/HD, significantly contributed to the prediction of EF task performance. No EF deficits were associated with ODD/CD. The presence of comorbid AD/HD accounts for the EF deficits in children with comorbid AD/HD+ODD/CD. These results suggest that EF deficits are unique to AD/HD and support the model proposed by R. A. Barkley (1997).17 p

Working Effectively with People with Attention Deficit/ Hyperactivity Disorder

This brochure on People with Attention Deficit/Hyperactivity Disorder and the Americans with Disabilities Act (ADA) is one of a series on human resources practices and workplace accommodations for persons with disabilities edited by Susanne M. Bruyère, Ph.D., CRC, SPHR, Director, Program on Employment and Disability, School of Industrial and Labor Relations – Extension Division, Cornell University. Cornell University was funded in the early 1990’s by the U.S. Department of Education National Institute on Disability and Rehabilitation Research as a National Materials Development Project on the employment provisions (Title I) of the ADA (Grant #H133D10155). These updates, and the development of new brochures, have been funded by Cornell’s Program on Employment and Disability, the Pacific Disability and Business Technical Assistance Center, and other supporters

A comprehensive investigation of memory impairment in attention deficit hyperactivity disorder and oppositional defiant disorder

We conducted a comprehensive and systematic assessment of memory functioning indrug-naïve boys with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). Boys performed verbal and spatial working memory (WM) component (storage and central executive) and verbal and spatial storage load tasks, and the spatial span, spatial executive WM, spatial recognition memory and verbal recognition memory tasks from the Cambridge Neuropsychological Test Automated Battery. Groups comprised: (a) ADHD only (N = 21); (b) ADHD+ODD (N = 27); (c) ODD only (N = 21); and (d) typically developing (TYP) boys (N = 26). Groups were matched for age (M = 9.7 years) and sex (all boys). Confirmatory factor analyses confirmed the presence of five factors: verbal functioning, spatial functioning, WM storage, WM central executive and long-term memory (LTM). All three clinical groups demonstrated impaired memory performance. Boys with ODD and ODD+ADHD but not ADHD alone performed poorly on verbal memory tasks, whilst all three clinical groups showed impaired performance on spatial memory tasks. All three clinical groups performed poorly on the storage and central executive WM factors and the LTM factor. ADHD and ODD are characterised by impaired performance storage and central executive WM tasks and LTM tasks. This is, we believe, the first report of impaired WM and LTM performance in ODD. This study suggests that verbal memory difficulties are more closely associated with ODD than ADHD symptoms and that combined ADHD+ODD represents a true comorbidity. The data also support a small but growing number of suggestions in the literature of impaired LTM in ADHD

Prenatal Nicotine Exposure as a Teratogen in Neurological Pathways

Attention-deficit/hyperactivity disorder (ADHD) is the most heritable and commonly diagnosed childhood psychiatric disorder with 4% of all children being diagnosed with this disorder. Prenatal smoking has been found to be a risk factor for ADHD, a disorder that has been believed to be linked to the fluctuation of dopamine levels. Prenatal nicotine exposure in the second trimester influences dopaminergic neurological pathways by altering dopamine release levels. The altered dopamine levels make the fetus brain more sensitive to the nicotine, causing the nicotine exposure to be more dangerous in causing ADHD symptoms. Prenatal nicotine exposure alters the neurological pathway of the neurotransmitters, ACh and dopamine, not only in the fetus but later in adolescence too. When nicotine enters the body, it is distributed quickly through the bloodstream and into the Central Nervous System (CNS). Cigarette smoke interferes with customary placental function, and therefore the flow of nutrients and oxygen. The nAChRs increases the amount of dopamine released in the synaptic area. Functional changes in DRD4 receptors and in dopamine transporter number caused by genetic variations and prenatal smoking exposure results in changes in dopamine release; however, the relationship between prenatal nicotine exposure and ADHD symptoms was not changed by sociodemographic factors. Interventions should be set-up in order to urge women to quit smoking during their pregnancy. The present study has health significance in that the research will urge pregnant women to be cautious of smoking through proposed interventions