Complex effects of dyslexia risk factors account for ADHD-traits : evidence from two independent samples

Background: Developmental dyslexia (DD) and attention deficit/hyperactivity disorder (ADHD) are among the most common neurodevelopmental disorders, whose etiology involves multiple risk factors. DD and ADHD co-occur in the same individuals much more often than would be expected by chance. Several studies have found significant bivariate heritability, and specific genes associated with either DD or ADHD have been investigated for association in the other disorder. Moreover, there are likely to be gene-by-gene and gene-by-environment interaction effects (GxG and GxE, respectively) underlying the comorbidity between DD and ADHD. We investigated the pleiotropic effects of 19 SNPs spanning five DD genes (DYX1C1, DCDC2, KIAA0319, ROBO1 and GRIN2B) and seven DD environmental factors (smoke, miscarriage, birth weight, breastfeeding, parental age, socioeconomic status and parental education) for main, either 1) genetic or 2) environmental, 3) G×G, and 4) G×E upon inattention and hyperactivity/impulsivity. We then attempted replication of these findings in an independent twin cohort. Methods: Marker-trait association was analyzed by implementing the Quantitative Transmission Disequilibrium Test (QTDT). Environmental associations were tested by partial correlations. GxG were investigated by a general linear model equation and a family-based association test. GxE were analyzed through a general test for GxE in sib-pair-based association analysis of quantitative traits. Results: DCDC2-rs793862 was associated with hyperactivity/impulsivity via G×G (KIAA0319) and G×E (miscarriage). Smoke was significantly correlated with hyperactivity/impulsivity. We replicated the DCDC2×KIAA0319 interaction upon hyperactivity/impulsivity in the twin cohort. Conclusions: DD genetic (DCDC2) and environmental factors (smoke and miscarriage) underlie ADHD-traits supporting a potential pleiotropic effect

Strong motion deficits in dyslexia associated with DCDC2 gene alteration

Dyslexia is a specific impairment in reading that affects 1 in 10 people. Previous studies have failed to isolate a single cause of the disorder, but several candidate genes have been reported. We measured motion perception in two groups of dyslexics, with and without a deletion within the DCDC2 gene, a risk gene for dyslexia. We found impairment for motion particularly strong at high spatial frequencies in the population carrying the deletion. The data suggest that deficits in motion processing occur in a specific genotype, rather than the entire dyslexia population, contributing to the large variability in impairment of motion thresholds in dyslexia reported in the literature

Working memory mediates the effects of gestational age at birth on expressive language development in children

Objective: This study tested the role of temporary memory, measured by phonological short-term memory (pSTM) and verbal working memory (vWM), as a mediator of the effect of 3 putative risk factors (i.e., socioeconomic status, home literacy environment, birth gestational age) upon expressive and receptive language. Method: A community-based sample of 646 Italian children aged 6-11 years was assessed with a comprehensive battery of language and cognitive tests. A mediation analysis was used to examine whether memory mediates environmental/biological effects on language. Results: The results demonstrated a developmental cascade of effects, whereby the duration of pregnancy drives vWM functioning that, in turn, may affect expressive linguistic outcome Conclusion: Treatments focused on vWM, specifically to preterm children, may improve their language development, with enduring consequences on educational and psychosocial outcome

Development and predictors of reading skills in a 5‐year Italian longitudinal study

Limited longitudinal studies have explored the development of reading, along with its predictors, in a language characterized by shallow orthography and a simple syllabic structure. In a 5-year longitudinal study, we investigated the development of reading skills in 327 Italian-speaking children (male: n = 180, 55%) from Grade 1 (mean age = 6.16 +/- 0.28) to Grade 5 (mean age = 10.82 +/- 0.31). We tested their reading performance at the end of each school year (Grade 1-5) and examined the impact of early cognitive factors (phonological awareness-PA, verbal short-term memory-vSTM, and non-verbal intelligence), environmental factors (socioeconomic status) as well as Grade 1 reading proficiency on subsequent reading development. A linear development of reading skills was found in both children classified as typical readers and those with reading disabilities. Non-verbal intelligence, PA, vSTM and reading proficiency at the end of Grade 1 predicted reading development throughout primary school (reading speed: R2-Intercept = 61.8%; R2-Slope = 12.9%, and reading accuracy: R2-Intercept = 40.1%; R2-Slope = 22.2%). The stability of reading performance across school grades highlights the significance of early reading skills as a marker and target for early intervention programs.Highlights To investigate reading development throughout primary school in an Italian-speaking sample, and the impact of early cognitive and environmental predictors. Reading development was linear and predicted by early cognitive skills, as assessed by repeated measures ANOVAs and growth curve modelling. These findings highlight the importance of supporting reading development as early as the end of Grade 1

Selecting the Most Relevant Brain Regions to Classify Children with Developmental Dyslexia and Typical Readers by Using Complex Magnocellular Stimuli and Multiple Kernel Learning

Increasing evidence supports the presence of deficits in the visual magnocellular (M) system in developmental dyslexia (DD). The M system is related to the fronto-parietal attentional network. Previous neuroimaging studies have revealed reduced/absent activation within the visual M pathway in DD, but they have failed to characterize the extensive brain network activated by M stimuli. We performed a multivariate pattern analysis on a Region of Interest (ROI) level to differentiate between children with DD and age-matched typical readers (TRs) by combining full-field sinusoidal gratings, controlled for spatial and temporal frequencies and luminance contrast, and a coherent motion (CM) sensitivity task at 6%-CML6, 15%-CML15 and 40%-CML40. ROIs spanning the entire visual dorsal stream and ventral attention network (VAN) had higher discriminative weights and showed higher act1ivation in TRs than in children with DD. Of the two tasks, CM had the greatest weight when classifying TRs and children with DD in most of the ROIs spanning these streams. For the CML6, activation within the right superior parietal cortex positively correlated with reading skills. Our approach highlighted the dorsal stream and the VAN as highly discriminative areas between children with DD and TRs and allowed for a better characterization of the “dorsal stream vulnerability” underlying DD

Selecting the Most Relevant Brain Regions to Classify Children with Developmental Dyslexia and Typical Readers by Using Complex Magnocellular Stimuli and Multiple Kernel Learning

Increasing evidence supports the presence of deficits in the visual magnocellular (M) system in developmental dyslexia (DD). The M system is related to the fronto-parietal attentional network. Previous neuroimaging studies have revealed reduced/absent activation within the visual M pathway in DD, but they have failed to characterize the extensive brain network activated by M stimuli. We performed a multivariate pattern analysis on a Region of Interest (ROI) level to differentiate between children with DD and age-matched typical readers (TRs) by combining full-field sinusoidal gratings, controlled for spatial and temporal frequencies and luminance contrast, and a coherent motion (CM) sensitivity task at 6%-CML6, 15%-CML15 and 40%-CML40. ROIs spanning the entire visual dorsal stream and ventral attention network (VAN) had higher discriminative weights and showed higher act1ivation in TRs than in children with DD. Of the two tasks, CM had the greatest weight when classifying TRs and children with DD in most of the ROIs spanning these streams. For the CML6, activation within the right superior parietal cortex positively correlated with reading skills. Our approach highlighted the dorsal stream and the VAN as highly discriminative areas between children with DD and TRs and allowed for a better characterization of the “dorsal stream vulnerability” underlying DD

Complex effects of dyslexia risk factors account for ADHD traits: evidence from two independent samples

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