Polymorphisms of the Dopamine D4 Receptor, Clinical Outcome, and Cortical Structure in Attention-Deficit/Hyperactivity Disorder

Shaw, Philip; Gornick, Michele C.; Lerch, Jason P.; Addington, Anjené; Seal, Jeffrey; Greenstein, Deanna; Sharp, Wendy; Evans, Alan C.; Giedd, Jay N.; Castellanos, F. Xavier; Rapoport, Judith L.

doi:10.1001/archpsyc.64.8.921

Cited by 220 publications

(178 citation statements)

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“…This indicates that deviance, rather than delay, characterizes the development of co-existing motor coordination problems over age in ADHD. This is contrary to older views but in accordance with more recent evidence of the (partial) persistence of structural brain abnormalities (Hall 1988;Castellanos et al 2002;Shaw 2007).…”

Section: Discussionsupporting

confidence: 70%

Motor coordination problems in children and adolescents with ADHD rated by parents and teachers: effects of age and gender

et al. 2007

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Summary. Objective. ADHD is frequently accompanied by motor coordination problems. However, the co-occurrence of poor motor performance has received less attention in research than other coexisting problems in ADHD. The underlying mechanisms of this association remain unclear. Therefore, we investigated the prevalence of motor coordination problems in a large sample of children with ADHD, and the relationship between motor coordination problems and inattentive and hyperactive=impulsive symptoms. Furthermore, we assessed whether the association between ADHD and motor coordination problems was comparable across ages and was similar for both genders.Method. We investigated 486 children with ADHD and 269 normal controls. Motor coordination problems were rated by parents (Developmental Coordination Disorder Questionnaire) and teachers (Groningen Motor Observation Scale).Results. Parents and teachers reported motor coordination problems in about one third of children with ADHD. Problems of fine and gross motor skills, coordination skills and motor control were all related to inattentive rather than hyperactive=impulsive symptoms. Relative to controls, motor coordination problems in ADHD were still present in teenagers according to parents; the prevalence diminished somewhat according to teachers. Boys and girls with ADHD were comparably affected, but motor performance in controls was better in girls than in boys.Conclusions. Motor coordination problems were reported in one third of children with ADHD and affected both boys and girls. These problems were also apparent in adolescents with ADHD. Clinicians treating children with ADHD should pay attention to co-occurring motor coordination problems because of the high prevalence and the negative impact of motor coordination problems on daily life.

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Section: Discussionsupporting

confidence: 70%

Motor coordination problems in children and adolescents with ADHD rated by parents and teachers: effects of age and gender

et al. 2007

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“…For instance, right parietal cortical normalization accompanied clinical improvement , and progressive volume loss of the inferior posterior lobes of the cerebellum accompanied persistence of ADHD (Mackie et al, 2007). Likewise, persistent ADHD is linked to a progressive loss of hippocampal volume (Shaw et al, 2007b). Stimulant drug treatment is associated with normalization of regional trajectories (Shaw et al, 2009).…”

Section: Mri Of Brain Anatomy In Atypical Pediatric Developmentmentioning

confidence: 99%

Child Psychiatry Branch of the National Institute of Mental Health Longitudinal Structural Magnetic Resonance Imaging Study of Human Brain Development

Giedd

Raznahan

Alexander-Bloch

et al. 2014

Neuropsychopharmacol

292

213

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The advent of magnetic resonance imaging, which safely allows in vivo quantification of anatomical and physiological features of the brain, has revolutionized pediatric neuroscience. Longitudinal studies are useful for the characterization of developmental trajectories (ie, changes in imaging measures by age). Developmental trajectories (as opposed to static measures) have proven to have greater power in discriminating healthy from clinical groups and in predicting cognitive/ behavioral measures, such as IQ. Here we summarize results from an ongoing longitudinal pediatric neuroimaging study that has been conducted at the Child Psychiatry Branch of the National Institute of Mental Health since 1989. Developmental trajectories of structural MRI brain measures from healthy youth are compared and contrasted with trajectories in attentiondeficit/hyperactivity disorder (ADHD) and childhood-onset schizophrenia. Across ages 5-25 years, in both healthy and clinical populations, white matter volumes increase and gray matter volumes follow an inverted U trajectory, with peak size occurring at different times in different regions. At a group level, differences related to psychopathology are seen for gray and white matter volumes, rates of change, and for interconnectedness among disparate brain regions.

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“…These delays in ADHD were most prominent in the lateral prefrontal cortex, especially the superior and DLPFC regions. In a separate study combining cortical thickness and genetics, Shaw et al (2007b) reported that possession of the dopamine D4 receptor (DRD4) 7-repeat allele in healthy children and ADHD was associated with significant cortical thinning of multiple regions including the OFC, inferior prefrontal cortex, and posterior parietal cortex. These brain regions were generally thinner in ADHD patients than in controls, although the matter is complex as ADHD patients with the 7-repeat allele fared better clinically, suggesting further study is required.…”

Section: Selected Adhd Imaging Datamentioning

confidence: 99%

“…Genetic influences on the neural circuitry of attention need to be explored further. Work has already been published that begins to link genotype and/or familial linkage with structural findings in ADHD (Casey et al, 2007a;Monuteaux et al, 2008;Shaw et al, 2007b) and to cognitive/executive function in healthy humans (Fan et al, 2003). Koten et al (2009) recently reported data from healthy twins that are very relevant to ADHD, as they showed how specific genetic factors could affect fMRI activation patterns within the brain regions of the CFP cognitive/attention network.…”

Section: Multimodal Imaging and Technique Refinementmentioning

confidence: 99%

Attention-Deficit/Hyperactivity Disorder and Attention Networks

Bush

2009

Neuropsychopharmacol

301

251

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Research attempting to elucidate the neuropathophysiology of attention-deficit/hyperactivity disorder (ADHD) has not only shed light on the disorder itself, it has simultaneously provided new insights into the mechanisms of normal cognition and attention. This review will highlight and integrate this bidirectional flow of information. Following a brief overview of ADHD clinical phenomenology, ADHD studies will be placed into a wider historical perspective by providing illustrative examples of how major models of attention have influenced the development of neurocircuitry models of ADHD. The review will then identify major components of neural systems potentially relevant to ADHD, including attention networks, reward/feedbackbased processing systems, as well as a 'default mode' resting state network. Further, it will suggest ways in which these systems may interact and be influenced by neuromodulatory factors. Recent ADHD imaging data will be selectively provided to both illustrate the field's current level of knowledge and to show how such data can inform our understanding of normal brain functions. The review will conclude by suggesting possible avenues for future research.

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Polymorphisms of the Dopamine D4 Receptor, Clinical Outcome, and Cortical Structure in Attention-Deficit/Hyperactivity Disorder

Cited by 220 publications

References 50 publications

Motor coordination problems in children and adolescents with ADHD rated by parents and teachers: effects of age and gender

Motor coordination problems in children and adolescents with ADHD rated by parents and teachers: effects of age and gender

Child Psychiatry Branch of the National Institute of Mental Health Longitudinal Structural Magnetic Resonance Imaging Study of Human Brain Development

Attention-Deficit/Hyperactivity Disorder and Attention Networks

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