Attention-deficit-hyperactivity disorder: an update.
ABSTRACT Attention-deficit-hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that impairs social, academic, and occupational functioning in children, adolescents, and adults. In patients with ADHD, neurobiologic research has shown a lack of connectivity in key brain regions, inhibitory control deficits, delayed brain maturation, and noradrenergic and dopaminergic dysfunction in multiple brain regions. The prevalence of this disorder in the United States is 6-9% in youth (i.e., children and adolescents) and 3-5% in adults. Prevalence rates for youth are similar worldwide. Children with ADHD are at greater risk than children without ADHD for substance abuse and delinquency whether or not they receive drug therapy; however, early treatment with psychoeducation as well as drug therapy and/or behavioral intervention may decrease negative outcomes of ADHD, including the rate of conduct disorder and adult antisocial personality disorder. Drug therapy is effective for all age groups, even preschoolers, and for late-onset ADHD in adults. Stimulants, such as methylphenidate and amphetamine, are the most effective therapy and have a good safety profile; although recent concerns of sudden unexplained death, psychiatric adverse effects, and growth effects have prompted the introduction of other therapies. Atomoxetine, a nonstimulant, has no abuse potential, causes less insomnia than stimulants, and poses minimal risk of growth effects. Other drug options include clonidine and guanfacine, but both can cause bradycardia and sedation. Polyunsaturated fatty acids (fish oil), acetyl-L-carnitine, and iron supplements (for youth with low ferritin levels) show promise in improving ADHD symptoms. As long-term studies show that at least 50% of youth are nonadherent with their drug therapy as prescribed over a 1-year period, long-acting formulations (administered once/day) may improve adherence. Comorbid conditions are common in patients with ADHD, but this patient population can be treated effectively with individualized treatment regimens of stimulants, atomoxetine, or bupropion, along with close monitoring.
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ABSTRACT: Background Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD). Purpose To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus. Methods Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined. Results The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner. Conclusion Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway.PLoS ONE 10/2014; 9(10):e108918. DOI:10.1371/journal.pone.0108918 · 3.53 Impact Factor
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ABSTRACT: Consistent with findings of aberrant macrostructural brain volume and neural activation in attentiondeficit/hyperactivity disorder (ADHD), diffusion magnetic resonance imaging (dMRI) studies of ADHD have converged to identify atypical findings within the underlying tissue microstructure. However, the direction and magnitude of diffusion metrics as well as the anatomical location of the findings varies considerably between studies. Thus, the biological interpretation of the aberrant neural microstructure in ADHD has been less clear partly due to clinical and technical confounding factors that have largely been unaccounted for in the ADHD dMRI literature. This review is intended to provide an overview of dMRI in vivo assessment of tissue microstructure, the general consistencies and inconsistencies from dMRI studies of ADHD, which is comprised primarily of diffusion tensor imaging (DTI) studies, and highlight the clinical and technical confounds that may contribute to the discrepant results and interpretations. Lastly, I will introduce advanced dMRI methods recently applied to ADHD that address some of the limitations inherent in conventional diffusion metrics. Future studies examining the neural microstructural correlates of ADHD may benefit by systematically accounting for some of the confounding factors discussed and by utilizing advanced dMRI methods. Rather than crudely identifying atypical yet highly variable microstructure properties, this approach could tease out consistent and reproducible tissue microstructure characteristics unique to certain aspects of ADHD.10/2013; 2(5):441-450. DOI:10.1166/jnsne.2013.1076
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ABSTRACT: One potential obstacle limiting our ability to clarify ADHD etiology is the heterogeneity within the disorder, as well as in typical samples. In this study, we utilized a community detection approach on 106 children with and without ADHD (aged 7-12 years), in order to identify potential subgroups of participants based on the connectivity of the reward system. Children with ADHD were compared to typically developing children within each identified community, aiming to find the community-specific ADHD characteristics. Furthermore, to assess how the organization in subgroups relates to behavior, we evaluated delay-discounting gradient and impulsivity-related temperament traits within each community. We found that discrete subgroups were identified that characterized distinct connectivity profiles in the reward system. Importantly, which connections were atypical in ADHD relative to the control children were specific to the community membership. Our findings showed that children with ADHD and typically developing children could be classified into distinct subgroups according to brain functional connectivity. Results also suggested that the differentiation in "functional" subgroups is related to specific behavioral characteristics, in this case impulsivity. Thus, combining neuroimaging data and community detection might be a valuable approach to elucidate heterogeneity in ADHD etiology and examine ADHD neurobiology. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.Developmental Cognitive Neuroscience 02/2015; 11:155-74. DOI:10.1016/j.dcn.2014.12.005 · 3.71 Impact Factor