Developmental Trajectories of the Corpus Callosum in Attention-Deficit/Hyperactivity Disorder

Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Biological psychiatry (Impact Factor: 10.26). 05/2011; 69(9):839-46. DOI: 10.1016/j.biopsych.2010.11.024
Source: PubMed


It was recently found that the development of typical patterns of prefrontal, but not posterior, cortical asymmetry is disrupted in right-handed youth with attention-deficit/hyperactivity disorder (ADHD). Using longitudinal data, we tested the hypothesis that there would be a congruent disruption in the growth of the anterior corpus callosum, which contains white matter tracts connecting prefrontal cortical regions.
Areas of five subregions of the corpus callosum were quantified using a semiautomated method from 828 neuroanatomic magnetic resonance scans acquired from 236 children and adolescents with ADHD (429 scans) and 230 typically developing youth (399 scans), most of whom had repeated neuroimaging. Growth rates of each diagnostic group were defined using mixed-model linear regression.
Right-handed participants with ADHD showed a significantly higher rate of growth in the anterior-most region of the corpus callosum (estimated annual increase in area of .97%, SEM .12%) than their typically developing peers (annual increase in area of .32% SEM .13%; t = 3.64, p = .0003). No significant diagnostic differences in growth rates were found in any other regions in right-handed participants, and no significant diagnostic differences were found in non-right-handed participants.
As hypothesized, we found anomalous growth trajectories in the anterior corpus callosum in ADHD. This disrupted anterior callosal growth may reflect, or even drive, the previously reported disruption in the development of prefrontal cortex asymmetry. The finding documents the dynamic, age-dependent nature of callosal and congruent prefrontal cortical abnormalities characterizing ADHD.

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Available from: Deanna (Dede) Greenstein
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    • "The typical development of human cerebral asymmetry has profound effect on the normal lateralization of cognitive and motor functions, such as language and handedness. Several studies have suggested the possible link of the disturbance of cerebral asymmetry with the pathogenesis of neurodevelopmental disorders [2], such as schizophrenia [3], autism [4] and ADHD [5]. "
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    ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is a common chronic neurodevelopmental disorder with a high heritability. Much evidence of hemisphere asymmetry has been found for ADHD probands from behavioral level, electrophysiological level and brain morphology. One previous research has reported possible association between BAIAP2, which is asymmetrically expressed in the two cerebral hemispheres, with ADHD in European population. The present study aimed to investigate the association between BAIAP2 and ADHD in Chinese Han subjects. A total of 1,397 ADHD trios comprised of one ADHD proband and their parents were included for family-based association tests. Independent 569 ADHD cases and 957 normal controls were included for case-control studies. Diagnosis was performed according to the DSM-IV criteria. Nine single nucleotide polymorphisms (SNPs) of BAIAP2 were chosen and performed genotyping for both family-based and case-control association studies. Transmission disequilibrium tests (TDTs) for family-based association studies showed significant association between the CA haplotype comprised by rs3934492 and rs9901648 with predominantly inattentive type (ADHD-I). For case-control study, chi-square tests provided evidence for the contribution of SNP rs4969239, rs3934492 and rs4969385 to ADHD and its two clinical subtypes, ADHD-I and ADHD-C. However, only the associations for ADHD and ADHD-I retained significant after corrections for multiplicity or logistic regression analyses adjusting the potential confounding effect of gender and age. These above results indicated the possible involvement of BAIAP2 in the etiology of ADHD, especially ADHD-I.
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    • "Because the generalization of the results of our case-control comparisons depends on the representativeness of our control group, we compared our control sample to published findings in other typically developing samples. Age-related changes in CC size in our control group are similar to changes in two very large mixed cross-sectional and longitudinal typically developing samples from other studies (Giedd et al., 1999; Gilliam et al., 2011). Similar to these larger samples, our control group shows an anterior–posterior gradient of age-related increase in CC area from early childhood to the early twenties (Section 3.2.2). "
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    ABSTRACT: Despite repeated findings of abnormal corpus callosum structure in autism, the developmental trajectories of corpus callosum growth in the disorder have not yet been reported. In this study, we examined corpus callosum size from a developmental perspective across a 30-year age range in a large cross-sectional sample of individuals with autism compared to a typically developing sample. Midsagittal corpus callosum area and the 7 Witelson subregions were examined in 68 males with autism (mean age 14.1 years; range 3-36 years) and 47 males with typical development (mean age 15.3 years; range 4-29 years). Controlling for total brain volume, increased variability in total corpus callosum area was found in autism. In autism, increased midsagittal areas were associated with reduced severity of autism behaviors, higher intelligence, and faster speed of processing (p=0.003, p=0.011, p=0.013, respectively). A trend toward group differences in isthmus development was found (p=0.029, uncorrected). These results suggest that individuals with autism benefit functionally from increased corpus callosum area. Our cross-sectional examination also shows potential maturational abnormalities in autism, a finding that should be examined further with longitudinal datasets.
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    • "In children with Attention Deficit/Hyperactivity Disorder (ADHD), various morphological changes have been reported in brain structures such as the thalamus (Ivanov et al., 2010), striatum (Castellanos et al., 1996), ventricular volumes (Castellanos et al., 1996), right prefrontal cortex (Rubia, 2005), and the corpus callosum (Hutchinson, Mathias, & Banich, 2008). Recently, longitudinal magnetic resonance imaging (MRI) studies showed that growth trajectories of anterior corpus callosum were different in adolescents with ADHD, indicating anomalies in developmental brain trajectories in these children (Gilliam et al., 2011). "

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