Brief Report: Circumscribed Attention in Young Children with Autism

School-aged children and adolescents with autism demonstrate circumscribed attentional patterns to nonsocial aspects of complex visual arrays (Sasson et al.2008). The current study downward extended these findings to a sample of 2–5 year-olds with autism and 2–5 year-old typically developing children. Eye-tracking was used to quantify discrete aspects of visual attention to picture arrays containing combinations of social pictures, pictures of objects frequently involved in circumscribed interests in persons with autism (e.g., trains), and pictures of more commonplace objects (e.g., clothing). The children with autism exhibited greater exploration and perseverative attention on objects related to circumscribed interests than did typically developing children. Results suggest that circumscribed attention may be an early emerging characteristic of autism

The First Year Inventory: A longitudinal follow-up of 12-month-olds to 3 years of age

The First Year Inventory (FYI) is a parent-report measure designed to identify 12-month old infants at risk for autism spectrum disorder (ASD). The FYI taps behaviors that indicate risk in the developmental domains of sensory-regulatory and social-communication functioning. This longitudinal study is a follow-up of 699 children at 3 years of age from a community sample whose parents completed the FYI when their children were 12 months old. Parents of all 699 children completed the Social Responsiveness Scale – Preschool version (SRS-P) and the Developmental Concerns Questionnaire (DCQ) to determine age 3 developmental outcomes. In addition, children deemed at-risk for ASD based on liberal cut points on the FYI, SRS-P, and/or DCQ were invited for in-person diagnostic evaluations. We found 9 children who had a confirmed diagnosis of ASD from the sample of 699. ROC analyses determined that a two-domain cutoff score yielded optimal classification of children: 31% of those meeting algorithm cut-offs had ASD and 85% had a developmental disability or concern by age three. These results suggest that the FYI is a promising tool for identifying 12-month old infants who are at risk for an eventual diagnosis of ASD

Age trends in visual exploration of social and nonsocial information in children with autism

Because previous studies of attention in autism spectrum disorders (ASD) have been restricted in age range examined, little is known about how these processes develop over the course of childhood. In this study we examined cross-sectional age effects on patterns of visual attention to social and nonsocial information in 43 typically developing children and 51 children with ASD ranging in age from 2 to 18. Results indicated a sharp increase in visual exploration with age and a decrease in perseverative and detail-focused attention for both groups of children. However, increased age was associated with greater increases in visual exploration for typically developing children than for those children with ASD. The developmental differences were most pronounced for attention to certain nonsocial stimuli as children with ASD demonstrated a disproportionate attentional bias for these stimuli from very early in life. Disproportionate visual attention to certain nonsocial objects relative to social stimuli in ASD spanned from early to late childhood, and thus may represent both an early and a persistent characteristic of the disorder

Generativity Abilities Predict Communication Deficits but not Repetitive Behaviors in Autism Spectrum Disorders

Individuals with Autism Spectrum Disorders (ASD) often demonstrate impaired generativity that is thought to mediate repetitive behaviors in autism (Turner in J Child Psychol Psychiatry, 40(6):839–849, 1999a). The present study evaluated generativity in children with and without ASD via the use-of-objects task (Turner in J Child Psychol Psychiatry, 40(2):189–201, 1999b) and an Animals Fluency Task (Lezak in Neuropsychological assessment. Oxford University Press, Oxford, 1995). Groups differed significantly on two of four metrics from the Animals Fluency Task and two of seven metrics from the Use of Objects task. In the ASD sample, no significant relations were found between generativity and repetitive behaviors. Significant relations were found, however, between performance on the Animals Fluency Task and communication symptoms. Results replicate reports of generativity deficits in ASD and suggest that impaired generativity may reflect communication deficits that are characteristic of the disorder

Performance of Children with Autism Spectrum Disorders on the Dimension-Change Card Sort Task

Restricted and repetitive behaviors in autism spectrum disorders have been conceptualized to reflect impaired executive functions. In the present study, we investigated the performance of 6–17-year-old children with and without an autism spectrum disorder on a dimension-change card sort task that explicitly indicated sorting rules on every trial. Diagnostic groups did not differ in speed of responses after the first rule switch or in speed or accuracy on blocks with mixed versus single sort rules. However, performance of the ASD group was significantly slower and less accurate overall than the typically-developing group. Furthermore, within the ASD group, poorer DCCS task performance did not predict more severe autism symptoms. Implications for the executive dysfunction theory of autism are discussed

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms