Cerebellar Development and Clinical Outcome in Attention Deficit Hyperactivity Disorder

Mackie, Susan

doi:10.1176/appi.ajp.164.4.647

Cited by 124 publications

(84 citation statements)

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“…Inclusion criteria included families of European descent with an ADHD proband (age [6][7][8][9][10][11][12][13][14][15][16][17][18]. Exclusionary criteria included prematurity ( < 36 weeks), mental retardation, major medical and neurological disorders, pervasive developmental disorder, psychoses and major mood disorders.…”

Section: Adhd Populationmentioning

confidence: 99%

“…4,5 Brain studies of patients with ADHD have shown abnormalities in frontal-striatal and cerebellar circuitry. 6,7 Although dopaminergic and noradrenergic medications are clinically effective, 8 animal models provide support for the involvement of additional molecular pathways. 9 Twin studies estimate a heritability of up to 90%, 10 indicating a substantial genetic contribution.…”

Section: Introductionmentioning

confidence: 99%

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Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes

et al. 2009

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Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD.

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Section: Adhd Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes

et al. 2009

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“…In lobules VIIIA and VIIIB, DAT-IR axons were present in both the external and the internal folia, but the density of immunoreactive axons was greater in the internal folia (Melchitzky and Lewis 2000). Another fMRI study demonstrated that the reduced volume of the inferior posterior cerebellar hemispheres is correlated with a poor clinical outcome in patients with ADHD (Mackie et al 2007). Thus, both the cerebellar vermis and the cerebellar posterior lobe have an important function in motor control (Ito 1984).…”

Section: Role Of Cerebellum In Inhibitory Controlmentioning

confidence: 99%

Pathophysiology of NSS in ADHD

Pasini

D’Agati

2009

The World Journal of Biological Psychiatry

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Attention deficit/hyperactivity disorder (ADHD) is the behavioural disorder most commonly diagnosed in childhood. In addition to the main symptoms of inattention, impulsiveness and hyperactivity, neurological soft signs (NSS) are often associated with ADHD. NSS are discrete motor and sensory disorders that cannot be linked to specific cerebral lesions. We review all the scientific contributions on NSS in ADHD. The conclusions support the presence of an alteration in the neural networks for motor control inhibition, at the base of the pathophysiology of NSS in children with ADHD, as well as a possible central role of dopamine in these neural circuits.

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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).…”

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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Cerebellar Development and Clinical Outcome in Attention Deficit Hyperactivity Disorder

Cited by 124 publications

References 0 publications

Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes

Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes

Pathophysiology of NSS in ADHD

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

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