Exploring 'The autisms' at a cognitive level

The autism spectrum is characterized by genetic and behavioral heterogeneity. However, it is still unknown whether there is a universal pattern of cognitive impairment in autism spectrum disorder (ASD) and whether multiple cognitive impairments are needed to explain the full range of behavioral symptoms. This study aimed to determine whether three widely acknowledged cognitive abnormalities (Theory of Mind (ToM) impairment, Executive Function (EF) impairment, and the presence of a Local Processing Bias (LB)) are universal and fractionable in autism, and whether the relationship between cognition and behavior is dependent on the method of behavioral assessment. Thirty-one high-functioning children with ASD and thirty-seven children with neurotypical development (NTD), comparable in age, gender and Intelligence Quotient (IQ), completed several tasks tapping into ToM, EF, and LB, and autistic symptomatology was assessed through parental and teacher questionnaires, parental interview and direct observation. We found that ToM and EF deficits differentiated the groups and some ToM and EF tasks were related to each other. ToM and EF were together able to correctly classify more than three-quarters of the children into cases and controls, despite relating to none of the specific behavioral measures. Only a small subgroup of individuals displayed a LB, which was unrelated to ToM and EF, and did not aid diagnostic classification, most likely contributing to non-diagnostic symptoms in a subgroup. Despite the characteristic heterogeneity of the autism spectrum, it remains a possibility therefore that a single cognitive cause may underlie the range of diagnostic symptoms in all individuals with autism

Enrichment of megabase-sized DNA molecules for single-molecule optical mapping and next-generation sequencing

Abstract Next-generation sequencing (NGS) has caused a revolution, yet left a gap: long-range genetic information from native, non-amplified DNA fragments is unavailable. It might be obtained by optical mapping of megabase-sized DNA molecules. Frequently only a specific genomic region is of interest, so here we introduce a method for selection and enrichment of megabase-sized DNA molecules intended for single-molecule optical mapping: DNA from a human cell line is digested by the NotI rare-cutting enzyme and size-selected by pulsed-field gel electrophoresis. For demonstration, more than 600 sub-megabase- to megabase-sized DNA molecules were recovered from the gel and analysed by denaturation-renaturation optical mapping. Size-selected molecules from the same gel were sequenced by NGS. The optically mapped molecules and the NGS reads showed enrichment from regions defined by NotI restriction sites. We demonstrate that the unannotated genome can be characterized in a locus-specific manner via molecules partially overlapping with the annotated genome. The method is a promising tool for investigation of structural variants in enriched human genomic regions for both research and diagnostic purposes. Our enrichment method could potentially work with other genomes or target specified regions by applying other genomic editing tools, such as the CRISPR/Cas9 system

Single-molecule DNA-mapping and whole-genome sequencing of individual cells

To elucidate cellular diversity and clonal evolution in tissues and tumors, one must resolve genomic heterogeneity in single cells. To this end, we have developed low-cost, mass-producible micro-/nanofluidic chips for DNA extraction from individual cells. These chips have modules that collect genomic DNA for sequencing or map genomic structure directly, on-chip, with denaturation-renaturation (D-R) optical mapping [Marie R, et al. (2013) Proc Natl Acad Sci USA 110:4893-4898]. Processing of single cells from the LS174T colorectal cancer cell line showed that D-R mapping of single molecules can reveal structural variation (SV) in the genome of single cells. In one experiment, we processed 17 fragments covering 19.8 Mb of the cell's genome. One megabase-large fragment aligned well to chromosome 19 with half its length, while the other half showed variable alignment. Paired-end single-cell sequencing supported this finding, revealing a region of complexity and a 50-kb deletion. Sequencing struggled, however, to detect a 20-kb gap that D-R mapping showed clearly in a megabase fragment that otherwise mapped well to the reference at the pericentromeric region of chromosome 4. Pericentromeric regions are complex and show substantial sequence homology between different chromosomes, making mapping of sequence reads ambiguous. Thus, D-R mapping directly, from a single molecule, revealed characteristics of the single-cell genome that were challenging for short-read sequencing

Clinician-rated mental health in outpatient child and adolescent mental health services: associations with parent, teacher and adolescent ratings

<p>Abstract</p> <p>Background</p> <p>Clinician-rated measures are used extensively in child and adolescent mental health services (CAMHS). The Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) is a short clinician-rated measure developed for ordinary clinical practice, with increasing use internationally. Several studies have investigated its psychometric properties, but there are few data on its correspondence with other methods, rated by other informants. We compared the HoNOSCA with the well-established Achenbach System of Empirically Based Assessment (ASEBA) questionnaires: the Child Behavior Checklist (CBCL), the Teacher's Report Form (TRF), and the Youth Self-Report (YSR).</p> <p>Methods</p> <p>Data on 153 patients aged 6-17 years at seven outpatient CAMHS clinics in Norway were analysed. Clinicians completed the HoNOSCA, whereas parents, teachers, and adolescents filled in the ASEBA forms. HoNOSCA <it>total score </it>and nine of its scales were compared with similar ASEBA scales. With a multiple regression model, we investigated how the ASEBA ratings predicted the clinician-rated HoNOSCA and whether the different informants' scores made any unique contribution to the prediction of the HoNOSCA scales.</p> <p>Results</p> <p>We found moderate correlations between the total problems rated by the clinicians (HoNOSCA) and by the other informants (ASEBA) and good correspondence between eight of the nine HoNOSCA scales and the similar ASEBA scales. The exception was HoNOSCA scale 8 <it>psychosomatic symptoms </it>compared with the ASEBA s<it>omatic problems </it>scale. In the regression analyses, the CBCL and TRF <it>total problems </it>scores together explained 27% of the variance in the HoNOSCA <it>total scores </it>(23% for the age group 11-17 years, also including the YSR). The CBCL provided unique information for the prediction of the HoNOSCA <it>total score</it>, HoNOSCA scale 1 <it>aggressive behaviour</it>, HoNOSCA scale 2 <it>overactivity or attention problems</it>, HoNOSCA scale 9 <it>emotional symptoms</it>, and HoNOSCA scale 10 <it>peer problems; </it>the TRF for all these except HoNOSCA scale 9 <it>emotional symptoms; </it>and the YSR for HoNOSCA scale 9 <it>emotional symptoms </it>only.</p> <p>Conclusion</p> <p>This study supports the concurrent validity of the HoNOSCA. It also demonstrates that parents, teachers and adolescents all contribute unique information in relation to the clinician-rated HoNOSCA, indicating that the HoNOSCA ratings reflect unique perspectives from multiple informants.</p

250 labels used to stigmatise people with mental illness

<p>Abstract</p> <p>Background</p> <p>The stigma against people with mental illness is a major barrier to help-seeking in young people for mental health problems. The objective of this study was to investigate the extent of stigma in relation to treatment avoidance in 14 year-old school students in England in relation to how they refer to people with mental illness.</p> <p>Methods</p> <p>This is a qualitative, cross-sectional study. The data were gathered as part of the baseline assessment for an intervention study intended to reduce stigma among 14 year old school students. The participating schools were two grammar (selective) schools and three comprehensive (non-selective) schools. At the start of the lesson, the students were asked 'What sorts of words or phrases might you use to describe someone who experiences mental health problems?' Words and terms used to refer to mental illness were enumerated. Using the grounded theory approach, words and terms were grouped in terms of their denotative and connotative meanings. Labels were then derived to capture the key themes attached by the students to the concepts of mental illness. The frequencies of occurrence for each word were also tabulated.</p> <p>Results</p> <p>400 of the 472 participating students (85%) provided 250 words and terms to describe a person with mental illness. Five themes were identified from the data. The first theme called 'popular derogatory terms' (116 items) accounted for nearly half of the words examined. The second theme occurred less often and was described as 'negative emotional state' (61 items). The third theme demonstrated the confusion of young people between physical disabilities, learning difficulties and mental health problems (38 items). The use of psychiatric diagnoses (15 items) and terms related to violence (9 items) were unexpectedly uncommon.</p> <p>Conclusion</p> <p>Our findings suggest the hypothesis that help-seeking by mentally ill young people may be improved by interventions that address both their lack of factual information about mental illness, and those which reduce their strong negative emotional reactions towards people with mental illness.</p

International comparisons of behavioral and emotional problems in preschool children: parents’ reports from 24 societies

International comparisons were conducted of preschool children’s behavioral and emotional problems as reported on the Child Behavior Checklist for Ages 1½–5 by parents in 24 societies (N¼19,850). Item ratings were aggregated into scores on syndromes; Diagnostic and Statistical Manual of Mental Disorders–oriented scales; a Stress Problems scale; and Internalizing, Externalizing, and Total Problems scales. Effect sizes for scale score differences among the 24 societies ranged from small to medium (3–12%). Although societies differed greatly in language, culture, and other characteristics, Total Problems scores for 18 of the 24 societies were within 7.1 points of the omnicultural mean of 33.3 (on a scale of 0–198). Gender and age differences, as well as gender and age interactions with society, were all very small (effect sizes<1%). Across all pairs of societies, correlations between mean item ratings averaged .78, and correlations between internal consistency alphas for the scales averaged .92, indicating that the rank orders of mean item ratings and internal consistencies of scales were very similar across diverse societies

Do Cognitive Deficits Persist Into Adolescence in Autism

SEVERAL THEORIES HAVE ATTEMPTED TO CHARACTERISE AUTISM SPECTRUM DISORDERS (ASDS) AT THE COGNITIVE LEVEL, MOST NOTABLY: THEORY OF MIND (TOM), EXECUTIVE FUNCTION (EF), AND A LOCAL PROCESSING BIAS (LB). THE AIM OF THIS STUDY WAS TO INVESTIGATE HOW THESE COGNITIVE FUNCTIONS DEVELOP OVER TIME: The three cognitive domains (ToM, EF, and LB) were examined in a group of high-functioning children (age: 8-12, mean 10.85; IQ: 78-139, mean 105.48) with ASD and a matched group of children with neurotypical development (NTD) (IQ: 75-145, mean: 109.47), and several tasks were used within each domain to ensure the validity of the cognitive measures. Approximately 3 years later (mean age: 14.34), all children and their families were invited to participate in the follow-up (ASD, N = 21; NTD, N = 30). While the understanding of other's minds does improve from childhood to adolescence, ToM impairment persists in adolescents with ASD relative to their peers. Likewise, a development in EF was observed in the ASD group, while no significant improvement was seen in the NTD group, leading the ASD group to catch up in this domain. We did not detect any group differences at any time point regarding local bias processing (LB). Individual patterns of development were seen, but remarkably, ToM deficits were present in every child with ASD in whom we could detect any cognitive impairment at baseline, and a similar pattern was found at follow-up. These findings indicate that ToM is a persistent cognitive deficit in ASD. LAY SUMMARY: This was the first study to investigate the development of three well-known cognitive functions into adolescence: While the understanding of other's minds improves from childhood to adolescence, adolescents with ASD are still impaired relative to their peers. The EFs, however, seem to improve to a neurotypical level in ASD as children enter adolescence, while local processing bias seems to differentiate the groups only in early childhood