Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder

Giedd, Jay N.; Castellanos, F. Xavier; Bj, Casey; Kozuch, Patricia; King, Abby C.; Sd, Hamburger; Jl, Rapoport

doi:10.1176/ajp.151.5.665

Cited by 341 publications

(17 citation statements)

References 21 publications

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“…This could be seen as a parallel to the frequently described macrocephaly in human 16p11.2 deletion patients and other types of ASD (Courchesne et al, 2007). There is also an apparent decrease in the size of the corpus callosum, which has been repeatedly observed in ASD and ADHD (Giedd et al, 1994 and Gilliam et al, 2011), as well as mouse models for ASD (Ellegood et al, 2013 and Wahlsten et al, 2003). The 16p11+/− mice show hyperactivity, a potential correlate for ADHD observed in 16p11.2 patients (Shinawi et al, 2010).…”

Section: Discussionmentioning

confidence: 72%

Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome

et al. 2014

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Summary A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11+/−). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2+) and fewer dopamine-sensitive (Drd1+) neurons in deep layers of cortex. Electrophysiological recordings of Drd2+ MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11+/− mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11+/− mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism.

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Section: Discussionmentioning

confidence: 72%

Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome

et al. 2014

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“…The putamen is innervated by neurons from the primary motor, premotor, supplementary motor, and somotosensory cortices, whereas the caudate receives input from frontal eye fields and association areas of the frontal and parietal lobes (Cote and Crutcher, 1990; Giedd et al, 1994). In the present study, the absolute, but not relative volume of the putamen was significantly smaller in the FAS/PFAS group relative to the SE/AE, ND/AE and Control groups.…”

Section: Discussionmentioning

confidence: 99%

Magnetic Resonance Imaging Outcomes From a Comprehensive Magnetic Resonance Study of Children With Fetal Alcohol Spectrum Disorders

Astley

Aylward

Olson

et al. 2009

Alcoholism Clin & Exp Res

207

240

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Background Magnetic resonance (MR) technology offers non-invasive methods for in vivo assessment of neuroabnormalities. Methods A comprehensive neuropsychological/psychiatric battery, coupled with MR imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) assessments, were administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified, and distinguish diagnostic subclassifications across the spectrum. The four study groups included: 1. FAS/Partial FAS; 2. Static Encephalopathy/Alcohol Exposed (SE/AE); 3. Neurobehavioral Disorder/Alcohol Exposed (ND/AE) as diagnosed with the FASD 4-Digit Code; and 4. healthy peers with no prenatal alcohol exposure. Presented here are the MRI assessments used to compare the sizes of brain regions between the four groups. The neuropsychological/behavioral, MRS, and fMRI outcomes are reported separately. Results Progressing across the four study groups from Controls to ND/AE to SE/AE to FAS/PFAS, the mean absolute size of the total brain, frontal lobe, caudate, putamen, hippocampus, cerebellar vermis, and corpus callosum length decreased incrementally and significantly. The FAS/PFAS group (the only group with the 4-Digit FAS facial phenotype) had disproportionately smaller frontal lobes relative to all other groups. The FAS/PFAS and SE/AE groups (the two groups with the most severe CNS dysfunction) had disproportionately smaller caudate regions relative to the ND/AE and Control groups. The prevalence of subjects in the FAS/PFAS, SE/AE, and ND/AE groups that had one or more brain regions, two or more standard deviations below the mean size observed in the Control group was78%, 58%, and 43%, respectively . Significant correlations were observed between size of brain regions and level of prenatal alcohol exposure, magnitude of FAS facial phenotype, and level of CNS dysfunction. Conclusions MRI provided further validation that ND/AE, SE/AE, and FAS/PFAS, as defined by the FASD 4-Digit Code, are three clinically distinct and increasingly more affected diagnostic subclassifications under the umbrella of FASD. Neurostructural abnormalities are present across the spectrum. MRI could importantly augment diagnosis of conditions under the umbrella of FASD, once population-based norms for structural development of the human brain are established.

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“…Moreover, HOE 642-treated animals exhibited a reduced loss of MBP and thicker ipsilateral CC compared with HI animals. Damage or agenesis of the CC in children is associated with attention deficit disorder and developmental coordination disorder [27,28]. Both of these clinical disorders are characterized by impairments of posture, motor coordination and sensorimotor coordination [27].…”

Section: Discussionmentioning

confidence: 99%

Chronic Neurological Deficits in Mice after Perinatal Hypoxia and Ischemia Correlate with Hemispheric Tissue Loss and White Matter Injury Detected by MRI

et al. 2011

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We investigated the effects of perinatal hypoxia-ischemia (HI) on brain injury and neurological functional outcome at postnatal day (P)30 through P90. HI was induced by exposing P9 mice to 8% O₂ for 55 min using the Vannucci HI model. Following HI, mice were treated with either vehicle control or Na⁺/H⁺ exchanger isoform 1 (NHE1) inhibitor HOE 642. The animals were examined by the accelerating rotarod test at P30 and the Morris water maze (MWM) test at P60. T₂-weighted MRI was conducted at P90. Diffusion tensor imaging (DTI) was subsequently performed in ex vivo brains, followed by immunohistochemical staining for changes in myelin basic protein (MBP) and neurofilament protein expression in the corpus callosum (CC). Animals at P30 after HI showed deficits in motor and spatial learning. T₂ MRI detected a wide spectrum of brain injury in these animals. A positive linear correlation was observed between learning deficits and the degree of tissue loss in the ipsilateral hemisphere and hippocampus. Additionally, CC DTI fractional anisotropy (FA) values correlated with MBP expression. Both FA and MBP values correlated with performance on the MWM test. HOE 642-treated mice exhibited improved spatial learning and memory, and less white matter injury in the CC. These findings suggest that HI-induced cerebral atrophy and CC injury contribute to the development of deficits in learning and memory, and that inhibition of NHE1 is neuroprotective in part by reducing white matter injury. T₂-weighted MRI and DTI are useful indicators of functional outcome after perinatal HI.

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Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder

Abstract: This finding supports theories of abnormal frontal lobe development and function in ADHD.

Cited by 341 publications

References 21 publications

Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome

Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome

Magnetic Resonance Imaging Outcomes From a Comprehensive Magnetic Resonance Study of Children With Fetal Alcohol Spectrum Disorders

Chronic Neurological Deficits in Mice after Perinatal Hypoxia and Ischemia Correlate with Hemispheric Tissue Loss and White Matter Injury Detected by MRI

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