Investigating the effects of copy number variants on reading and language performance.

BACKGROUND: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs). METHODS: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes). Then, we computed the correlation between measures of CNV genomic burden and the first principal component (PC) score derived from several continuous reading and language traits, both before and after adjustment for performance IQ. Finally, we screened the genome, probe-by-probe, for association with the PC scores, through two complementary analyses: we tested a binary CNV state assigned for the location of each probe (i.e., CNV+ or CNV-), and we analyzed continuous probe intensity data using FamCNV. RESULTS: No significant correlation was found between measures of CNV burden and PC scores, and no genome-wide significant associations were detected in probe-by-probe screening. Nominally significant associations were detected (p~10(-2)-10(-3)) within CNTN4 (contactin 4) and CTNNA3 (catenin alpha 3). These genes encode cell adhesion molecules with a likely role in neuronal development, and they have been previously implicated in autism and other neurodevelopmental disorders. A further, targeted assessment of candidate CNV regions revealed associations with the PC score (p~0.026-0.045) within CHRNA7 (cholinergic nicotinic receptor alpha 7), which encodes a ligand-gated ion channel and has also been implicated in neurodevelopmental conditions and language impairment. FamCNV analysis detected a region of association (p~10(-2)-10(-4)) within a frequent deletion ~6 kb downstream of ZNF737 (zinc finger protein 737, uncharacterized protein), which was also observed in the association analysis using CNV calls. CONCLUSIONS: These data suggest that CNVs do not underlie a substantial proportion of variance in reading and language skills. Analysis of additional, larger datasets is warranted to further assess the potential effects that we found and to increase the power to detect CNV effects on reading and language.

Sensitivity to structure in the speech signal by children with speech sound disorder and reading disability.

PURPOSE: Children with speech sound disorder (SSD) and reading disability (RD) have poor phonological awareness, a problem believed to arise largely from deficits in processing the sensory information in speech, specifically individual acoustic cues. However, such cues are details of acoustic structure. Recent theories suggest that listeners also need to be able to integrate those details to perceive linguistically relevant form. This study examined abilities of children with SSD, RD, and SSD+RD not only to process acoustic cues but also to recover linguistically relevant form from the speech signal. METHOD: Ten- to 11-year-olds with SSD (n=17), RD (n=16), SSD+RD (n=17), and Controls (n=16) were tested to examine their sensitivity to (1) voice onset times (VOT); (2) spectral structure in fricative-vowel syllables; and (3) vocoded sentences. RESULTS: Children in all groups performed similarly with VOT stimuli, but children with disorders showed delays on other tasks, although the specifics of their performance varied. CONCLUSION: Children with poor phonemic awareness not only lack sensitivity to acoustic details, but are also less able to recover linguistically relevant forms. This is contrary to one of the main current theories of the relation between spoken and written language development. LEARNING OUTCOMES: Readers will be able to (1) understand the role speech perception plays in phonological awareness, (2) distinguish between segmental and global structure analysis of speech perception, (3) describe differences and similarities in speech perception among children with speech sound disorder and/or reading disability, and (4) recognize the importance of broadening clinical interventions to focus on recognizing structure at all levels of speech analysis.

Do motivational incentives reduce the inhibition deficit in ADHD?

The primary goal of this study was to test three competing theories of ADHD: the inhibition theory, the motivational theory, and a dual deficit theory. Previous studies have produced conflicting findings about the effects of incentives on executive processes in ADHD. In the present study of 25 children with ADHD and 30 typically developing controls, motivation was manipulated within the Stop Task. Stop signal reaction time was examined, as well as reaction time, its variability, and the number of errors in the primary choice reaction time task. Overall, the pattern of results supported the inhibition theory over the motivational or dual deficit hypotheses, as main effects of group were found for most key variables (ADHD group was worse), whereas the group by reward interaction predicted by the motivational and dual deficit accounts was not found. Hence, as predicted by the inhibition theory, children with ADHD performed worse than controls irrespective of incentives.