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Background: 22q11.2 deletion syndrome (22q11DS) is the second most prevalent genetic syndrome and has a characteristic academic and behavioural phenotype. The primary objective of the current study was to examine the childhood predictors of written expression achievement in adolescents with 22q11DS. Written expression is an important skill that can impact an individual's overall academic performance, potentially resulting in increased levels of stress and exacerbation of psychiatric symptoms. Methods: A total of 119 participants were included in this study. Sixty-nine late adolescents with 22q11DS and 50 controls (consisting of a combined sample of 23 unaffected siblings of youth with 22q11DS and 27 community controls) participated in a 6-year longitudinal research project and received neuropsychological test batteries every 3 years. The Written Expression subtest of the Wechsler Individual Achievement Test-Second Edition was the primary outcome measure in the current project. Results: Findings indicated differences in childhood predictors of adolescent written expression between participants in the 22q11DS group and participants in the control group. Whereas childhood verbal IQ scores predicted adolescent written expression for participants in the control group, childhood executive function and language skills were unique predictors of adolescent written expression in individuals with 22q11DS. Conclusions: Childhood predictors of late adolescent written expression in 22q11DS differ in meaningful ways from predictors in the non-22q11DS population. These results offer some guidance on the underlying factors that may be useful to consider when developing written expression interventions for children with 22q11DS.

This study applied a Talairach-based automated parcellation method, originally proposed for adults, to the measurement of lobar brain regions in pediatric study groups. Manual measures of lobar brain regions in a sample of 15 healthy boys, girls and adults were used initially to revise the original Talairach-based grid to increase its applicability to pediatric brains. The applicability of the revised Talairach grid was then tested on an independent sample of five girls with Rett syndrome. As Tables 3 and 4 in the text demonstrate, sensitivity, specificity and positive predictive values either remained unchanged or increased as a result of revising the sectors to fit the brains of children. High levels of sensitivity and specificity were achieved for all revised Talairach-based calculations in relation to the manual measures. Both positive predictive values and intraclass correlations between volumetric measures produced by the revised automated and manual methods varied with the relative size of the brain region. Values were relatively low for smaller structures such as the brainstem and subcortical region, and high for lobar regions. These results suggest that the automated Talairach atlas-based parcellation method can produce sensitive and specific volumetric measures of lobar brain regions in both normal children and children with brain disorders. Accordingly, the method holds much promise for facilitating quantitative pediatric neuroimaging research.

In this study, we investigated the neuroanatomical similarities and differences between a pair of monozygotic, 7.5-year-old twin boys discordant for strictly defined autism, to identify neuroanatomical pathways that are impaired in individuals with autism. Although the unaffected twin did not fulfill the traditional diagnostic criteria for autism, he displayed constrictions in social interaction and play that were consistent with the broader phenotype for autism that has been described in nonautistic co-twins. Magnetic resonance imaging scans were obtained for each brother and compared with the scans of 5 age- and sex-matched unaffected peers. Quantitative analysis of brain anatomy revealed that the affected twin had markedly smaller caudate, amygdaloid, and hippocampal volumes, and smaller cerebellar vermis lobules VI and VII, in comparison with his brother. Both twins evidenced disproportionately reduced volumes of the superior temporal gyrus and the frontal lobe relative to the comparison sample. The results suggest the dysfunction of two separate but overlapping neuroanatomical pathways, ie, one subcortical network differentiating the twins from each other that may underlie the traditional neurobehavioral phenotype for strictly defined autism, and a second cortical network differentiating the twins from the comparison sample that may lead to the broader phenotype for autism.

New techniques in quantitative imaging are needed to accelerate understanding of brain development and function in children. In this study we evaluate the reliability and validity of an automated parcellation method for the measurement of large and small brain regions in normal and developmentally disabled children. We utilized an adaptation of the Talairach atlas to semi-automatically quantify brain volumes from 10 children with fragile X syndrome, 10 age- and gender-matched controls and 10 adult controls comparing them to 'gold standard' manually delineated regions. Excellent sensitivity, specificity, intra-class correlation and positive predictive value were achieved for large structures although results were less satisfactory for smaller structures, illustrating the limits of resolution of the method. Statistically significant differences in regional brain volumes were shown between males and females, children and adults, and individuals with fragile X and matched controls. This study demonstrates an automated method which rapidly and accurately quantifies large neuroanatomical structures, but not smaller structures. This method is sufficiently accurate to demonstrate some known anatomical differences in individuals with fragile X; the results suggest that this method could be applied to the assessment of brain volume in other neurodevelopmental disabilities.

Evidence from numerous structural magnetic resonance imaging (MRI) studies has converged to implicate mesial temporal lobe structures in the pathophysiology of several developmental and psychiatric disorders. Efforts to integrate the results of these studies are challenged, however, by the lack of consistency, detail and precision in published protocols for the manual measurement of the amygdala and hippocampus. In this study, we describe a highly detailed, standardized protocol for measuring the amygdala and the hippocampus. Within the context of this protocol, we tested the inter- and intra-rater reliability of two frequently cited methods for normalizing the anatomical position of the amygdala and hippocampus prior to measurement. One method consisted of creating a coronal data set in which images are rotated in a plane perpendicular to the long axis of the hippocampus. The second method consisted of creating a coronal data set in which images are rotated in a plane perpendicular to the axis connecting the anterior and posterior commissures. Inter- and intra-rater reliability coefficients (using the intraclass correlation) ranged from 0.80 to 0.98, indicating that both methods for positional normalization are highly reliable. In addition, we tested the validity of each method by comparing the temporal lobe anatomy of children with fragile X syndrome to a group of unaffected children matched by age and gender. We found that hippocampal volumes in children with fragile X were significantly increased when either rotational method was used. These results replicated previous findings, suggesting that either method can be validly applied to neuronanatomic studies of pediatric populations.

Reports of autistic behaviors were examined for 30 school-age girls with fragile X (fraX) and 31 age- and IQ-matched controls through a structured interview administered to each girl's parent(s). IQ scores were obtained for each participant; anxiety, neuroanatomical, and molecular-genetic data were derived for girls with fraX. Girls with fraX had significantly more autistic behaviors than controls. These behaviors were qualitatively similar to those reported for boys with fraX, but were not correlated with IQ. Anxiety in girls with fraX was positively correlated with abnormal social and communication behaviors; posterior cerebellar vermis area was negatively correlated with measures of communication and stereotypic/restricted behaviors. Severity of stereotypic/restricted behaviors was negatively correlated with the prevalence of active non-fraX chromosomes. Thus anxiety and posterior cerebellar area measures had distinct associations with subsets of autistic behaviors; these associations may have important implications for understanding the neurobiology of autism.