Sensory processing differences are reported both in children with ADHD and in children with autism. Given the substantial overlap between autism and ADHD, the current study examined which sensory ...features were uniquely predictive of autistic traits after controlling for ADHD symptoms, age, IQ, and sex in a sample of children and adolescents with autism aged 6-17 years.
The sample included 61 children and adolescents with autism. The Sensory Profile was used to examine Dunn's quadrant model (seeking, sensitivity, avoiding, registration), ADHD symptoms were measured using hyperactivity and attention problems BASC-2 T-scores, and autistic traits were measured using the AQ.
After controlling for age, IQ, sex, and ADHD symptoms, Dunn's sensitivity quadrant predicted autistic traits.
Findings provide insight into the phenotype of autism and ADHD. Sensory sensitivity may be unique to autism over and above elevated ADHD symptoms that are commonly seen in this population.
To assess the extent to which the trajectories of intellectual, academic achievement, executive functioning, attention, working memory, and emotion recognition tests will be predictive of psychosis ...in young adults with 22q11.2 deletion syndrome (22q11DS).
Eighty-two participants with 22q11DS were assessed for psychiatric disorders and neuropsychological functioning with validated instruments. Siblings and community controls were employed as comparison groups.
Individuals with 22q11DS differed significantly from siblings and controls in longitudinal trajectories of visual and auditory working memory as well as academic achievement. Longitudinal trajectories of cognitive set shifting, reading decoding, and emotion recognition predicted the presence of positive symptoms of psychosis in early adulthood. Cognitive set shifting improved at a slower rate for individuals with 22q11DS + psychosis than those without psychosis. Emotion recognition increased steadily in individuals without psychosis, whereas for those with psychosis, scores increased until approximately 15 years of age, at which point they began to decrease rapidly. A similar, but more subtle effect, was seen for reading decoding.
Our data are the first to go beyond IQ assessments in assessing longitudinal neuropsychological outcomes and risk for psychosis in 22q11DS. Individuals with 22q11DS who developed psychotic symptoms improved less appreciably and continued to demonstrate difficulties with cognitive flexibility relative to individuals with 22q11DS who did not have psychotic symptoms. Individuals with 22q11DS who developed psychosis had weaker reading skills in childhood and, after an initial improvement into adolescence, these individuals with psychosis had a decline in reading skills. In 22q11DS, cognitive deficits are both (a) traits that are preexisting and raise the risk for psychosis and (b) associated with the onset of psychotic symptoms. Future research should consider the extent to which cognitive set shifting and reading decoding are related to the Verbal IQ declines observed in the 22q11DS population.
We performed whole exome sequence (WES) to identify genetic modifiers on 184 individuals with 22q11.2 deletion syndrome (22q11DS), of whom 89 case subjects had severe congenital heart disease (CHD) ...and 95 control subjects had normal hearts. Three genes including JMJD1C (jumonji domain containing 1C), RREB1 (Ras responsive element binding protein 1), and SEC24C (SEC24 family member C) had rare (MAF < 0.001) predicted deleterious single-nucleotide variations (rdSNVs) in seven case subjects and no control subjects (p = 0.005; Fisher exact and permutation tests). Because JMJD1C and RREB1 are involved in chromatin modification, we investigated other histone modification genes. Eighteen case subjects (20%) had rdSNVs in four genes (JMJD1C, RREB1, MINA, KDM7A) all involved in demethylation of histones (H3K9, H3K27). Overall, rdSNVs were enriched in histone modifier genes that activate transcription (Fisher exact p = 0.0004, permutations, p = 0.0003, OR = 5.16); however, rdSNVs in control subjects were not enriched. This implicates histone modification genes as influencing risk for CHD in presence of the deletion.
•The depth of the attentional blink was stable from ages 7 to 15, and no different from adults.•Recovery time from the attentional blink decreased with age.•Two types of errors, swaps and temporal ...binding errors, decreased systematically with increasing age.
The ability to select targets from an ongoing stream of visual information is critical to the successful management of visual attention. The attentional blink (AB), a phenomenon elicited using rapid serial visual presentation, allows for the assessment of the limits of the temporal visual system, and is reflected in a decrease in accuracy in the detection of the second of two targets when it occurs within 200–500ms of a first target. Evidence regarding the development of the AB is mixed and appears to be dependent on the task demands. Here we present data examining the AB across middle childhood, early adolescence, and adulthood using a feature binding task. Participants were asked to detect and report the identity of two purple letters presented in a stream of black letters at a rate of 135ms/item. On this feature binding task, the depth of the AB was invariant across development but AB recovery occurred earlier with increasing age. Furthermore, the error data suggested important developments in temporal binding that were reflected both in a decrease in the number of swaps (where participants reverse the order of the targets but identify them correctly) and in the spread of temporal binding errors with age. These findings suggest that the characteristics of the AB and its development are task dependent and also suggest that the development of binding abilities in visual search tasks mirrors the time course of multisensory binding effects, perhaps suggesting a common mechanism.
This paper examined whether FreeSurfer-generated data differed between a fully-automated, unedited pipeline and an edited pipeline that included the application of control points to correct errors in ...white matter segmentation. In a sample of 30 individuals, we compared the summary statistics of surface area, white matter volumes, and cortical thickness derived from edited and unedited datasets for the 34 regions of interest (ROIs) that FreeSurfer (FS) generates. To determine whether applying control points would alter the detection of significant differences between patient and typical groups, effect sizes between edited and unedited conditions in individuals with the genetic disorder, 22q11.2 deletion syndrome (22q11DS) were compared to neurotypical controls. Analyses were conducted with data that were generated from both a 1.5 tesla and a 3 tesla scanner. For 1.5 tesla data, mean area, volume, and thickness measures did not differ significantly between edited and unedited regions, with the exception of rostral anterior cingulate thickness, lateral orbitofrontal white matter, superior parietal white matter, and precentral gyral thickness. Results were similar for surface area and white matter volumes generated from the 3 tesla scanner. For cortical thickness measures however, seven edited ROI measures, primarily in frontal and temporal regions, differed significantly from their unedited counterparts, and three additional ROI measures approached significance. Mean effect sizes for edited ROIs did not differ from most unedited ROIs for either 1.5 or 3 tesla data. Taken together, these results suggest that although the application of control points may increase the validity of intensity normalization and, ultimately, segmentation, it may not affect the final, extracted metrics that FS generates. Potential exceptions to and limitations of these conclusions are discussed.
Objective:Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of ...autism is underpinned by specific genotype-phenotype relationships.Methods:This international study included 547 individuals (mean age, 12.3 years SD=4.2, 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years SD=4.9, 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview–Revised and IQ testing.Results:The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%–97% of the variance, depending on the trait), whereas variability between groups was low (1%–21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits.Conclusions:Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.
Abstract Background 22q11DS is a multiple anomaly syndrome involving intellectual and behavioral deficits, and increased risk for schizophrenia. As cognitive remediation (CR) has recently been found ...to improve cognition in younger patients with schizophrenia, we investigated the efficacy, feasibility, and fidelity of a remote, hybrid strategy, computerized CR program in youth with 22q11DS. Methods A longitudinal design was implemented in which 21 participants served as their own controls. Following an eight month baseline period in which no interventions were provided, cognitive coaches met with participants remotely for CR via video conferencing three times a week over a targeted 8 month timeframe and facilitated their progress through the intervention, offering task-specific strategies. A subset of strategies were examined for fidelity. Outcomes were evaluated using a neurocognitive test battery at baseline, pre-treatment and post-treatment. Results All participants adhered to the intervention. The mean length of the treatment phase was 7.96 months. A moderately high correlation (intraclass correlation coefficient, 0.73) was found for amount and type of strategies offered by coaches. Participants exhibited significant improvements (ES = .36–.55, p ≤ .009) in working memory, shifting attention and cognitive flexibility. All significant models were driven by improvements in pre to post-treatment scores. Conclusions Based on our preliminary investigation, a remote, hybrid strategy, computerized CR program can be implemented with 22q11DS youth despite geographic location, health, and cognitive deficits. It appears effective in enhancing cognitive skills during the developmental period of adolescence, making this type of CR delivery useful for youth with 22q11DS transitioning into post-school environments.
Objective: To predict prodromal psychosis in adolescents with velocardiofacial syndrome (VCFS). Method: A total of 70 youth with VCFS, 27 siblings of youth with VCFS, and 25 community controls were ...followed from childhood (mean age = 11.8 years) into mid-adolescence (mean age = 15.0 years). Psychological tests measuring intelligence, academic achievement, learning/memory, attention, and executive functioning as well as measures of parent and clinician ratings of child psychiatric functioning were completed at both time points. Results: Major depressive disorder, oppositional defiant disorder, and generalized anxiety disorder diagnoses increased in the VCFS sample. With very low false positive rates, the best predictor of adolescent prodromal psychotic symptoms was parent ratings of childhood odd/eccentric symptoms and child performance on a measure of executive functioning, the Wisconsin Card Sorting Test. Conclusions: Similar to the non-VCFS prodromal psychosis literature, a combination of cognitive and psychiatric variables appears to predict psychosis in adolescence. A child with VCFS who screens positive is noteworthy and demands clinical attention. (Contains 5 tables.)
Compared to the large body of maternal mental health research for other pediatric disorders, we know far less about the experience of mothers of children with 22q11DS. This study investigates the ...coping methods, protective factors, and mental health of this population. These findings might lead to better support for 22q11DS maternal mental health. An international sample of 71 mothers (M = 40.5 years) of children with 22q11DS (M = 9.2 years) was recruited and completed an online survey assessing maternal mental health (symptoms of depression, anxiety, traumatic stress, general stress, and alcohol consumption), coping methods, and mental health protective factors (social support, dyadic adjustment, parenting competence). Maternal ratings of child mental health symptoms were also obtained. Mothers' self-report revealed a high percentage who screened positive for elevated levels of general stress (69%), hazardous alcohol consumption (30.9%), traumatic stress (33.8%), anxiety (26.8%), and depression (26.8%). After controlling for demographic variables and child mental health symptoms, maternal self-reported maladaptive coping methods were positively associated with maternal symptoms of depression, anxiety, stress, and traumatic stress. Reducing maladaptive coping methods may be a promising intervention for improving mental health in mothers of children with 22q11DS.
Objective:Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a more than 20-fold increased risk for developing schizophrenia. The aim of this study was to identify additional genetic ...factors (i.e., “second hits”) that may contribute to schizophrenia expression.Method:Through an international consortium, the authors obtained DNA samples from 329 psychiatrically phenotyped subjects with 22q11.2DS. Using a high-resolution microarray platform and established methods to assess copy number variation (CNV), the authors compared the genome-wide burden of rare autosomal CNV, outside of the 22q11.2 deletion region, between two groups: a schizophrenia group and those with no psychotic disorder at age ≥25 years. The authors assessed whether genes overlapped by rare CNVs were overrepresented in functional pathways relevant to schizophrenia.Results:Rare CNVs overlapping one or more protein-coding genes revealed significant between-group differences. For rare exonic duplications, six of 19 gene sets tested were enriched in the schizophrenia group; genes associated with abnormal nervous system phenotypes remained significant in a stepwise logistic regression model and showed significant interactions with 22q11.2 deletion region genes in a connectivity analysis. For rare exonic deletions, the schizophrenia group had, on average, more genes overlapped. The additional rare CNVs implicated known (e.g., GRM7, 15q13.3, 16p12.2) and novel schizophrenia risk genes and loci.Conclusions:The results suggest that additional rare CNVs overlapping genes outside of the 22q11.2 deletion region contribute to schizophrenia risk in 22q11.2DS, supporting a multigenic hypothesis for schizophrenia. The findings have implications for understanding expression of psychotic illness and herald the importance of whole-genome sequencing to appreciate the overall genomic architecture of schizophrenia.
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