Block design reconstruction skills: not a good candidate for an endophenotypic marker in autism research

Superior performance on block design tasks is reported in autistic individuals, although it is not consistently found in high-functioning individuals or individuals with Asperger Syndrome. It is assumed to reflect weak central coherence: an underlying cognitive deficit, which might also be part of the genetic makeup of the disorder. We assessed block design reconstruction skills in high-functioning individuals with autism spectrum disorders (ASD) from multi-incidence families and in their parents. Performance was compared to relevant matched control groups. We used a task that was assumed to be highly sensitive to subtle performance differences. We did not find individuals with ASD to be significantly faster on this task than the matched control group, not even when the difference between reconstruction time of segmented and pre-segmented designs was compared. However, we found individuals with ASD to make fewer errors during the process of reconstruction which might indicate some dexterity in mental segmentation. However, parents of individuals with ASD did not perform better on the task than control parents. Therefore, based on our data, we conclude that mental segmentation ability as measured with a block design reconstruction task is not a neurocognitive marker or endophenotype useful in genetic studies

Dissecting the Clinical Heterogeneity of Autism Spectrum Disorders through Defined Genotypes

BACKGROUND: The etiology of autism spectrum disorders (ASD) is largely determined by different genetic factors of variable impact. This genetic heterogeneity could be a factor to explain the clinical heterogeneity of autism spectrum disorders. Here, a first attempt is made to assess whether genetically more homogeneous ASD groups are associated with decreased phenotypic heterogeneity with respect to their autistic symptom profile. METHODOLOGY: The autistic phenotypes of ASD subjects with 22q11 deletion syndrome (22q11DS) and ASD subjects with Klinefelter Syndrome (KS) were statistically compared to the symptom profile of a large (genetically) heterogeneous ASD sample. Autism diagnostic interview-revised (ADI-R) variables were entered in different statistical analyses to assess differences in symptom homogeneity and the feasibility of discrimination of group-specific ASD-symptom profiles. PRINCIPAL FINDINGS: The results showed substantially higher symptom homogeneity in both the genetic disorder ASD groups in comparison to the heterogeneous ASD sample. In addition, a robust discrimination between 22q11-ASD and KS-ASD and idiopathic ASD phenotypes was feasible on the basis of a reduced number of autistic scales and symptoms. The lack of overlap in discriminating subscales and symptoms between KS-ASD and 22q11DS-ASD suggests that their autistic symptom profiles cluster around different points in the total diagnostic space of profiles present in the general ASD population. CONCLUSION: The findings of the current study indicate that the clinical heterogeneity of ASDs may be reduced when subgroups based on a specific genotype are extracted from the idiopathic ASD population. The current strategy involving the widely used ADI-R offers a relatively straightforward possibility for assessing genotype-phenotype ASD relationships. Reverse phenotype strategies are becoming more feasible, given the accumulating evidence for the existence of genetic variants of large effect in a substantial proportion of the ASD population

Two-year-olds at elevated risk for ASD can learn novel words from their parents

Children diagnosed with autism spectrum disorder (ASD) often have smaller vocabularies in infancy compared to typically-developing children. To understand whether their smaller vocabularies stem from problems in learning, our study compared a prospective risk sample of 18 elevated risk and 11 lower risk 24-month-olds on current vocabulary size and word learning ability using a paradigm in which parents teach their child words. Results revealed that both groups learned novel words, even though parents indicated that infants at elevated risk of ASD knew fewer words. This suggests that these early compromised vocabularies cannot be solely linked to difficulties in word formations

Standardized ADOS Scores: Measuring Severity of Autism Spectrum Disorders in a Dutch Sample

The validity of the calibrated severity scores on the ADOS as reported by Gotham et al. (J Autism Dev Disord 39: 693–705, 2009), was investigated in an independent sample of 1248 Dutch children with 1455 ADOS administrations (modules 1, 2 and 3). The greater comparability between ADOS administrations at different times, ages and in different modules, as reached by Gotham et al. with the calibrated severity measures, seems to be corroborated by the current study for module 1 and to a lesser extent for module 3. For module 2, the calibrated severity scores need to be further investigated within a sample that resembles Gotham’s sample in age and level of verbal functioning

Evaluation of the ADOS Revised Algorithm: The Applicability in 558 Dutch Children and Adolescents

The revised ADOS algorithms, proposed by Gotham et al. (J Autism Dev Disord 37:613–627, 2007), were investigated in an independent sample of 558 Dutch children (modules 1, 2 and 3). The revised algorithms lead to better balanced sensitivity and specificity for modules 2 and 3, without losing efficiency of the classification. Including the restricted repetitive behaviour domain in the algorithm contributes to a clinical ASD classification in modules 2 and 3. For module 1, the results indicate less improvement, probably due to the low-functioning population. In most groups, the advantages of the revised algorithms are achieved without losing the strength of the original algorithm

Standardized ADOS Scores: Measuring Severity of Autism Spectrum Disorders in a Dutch Sample

The validity of the calibrated severity scores on the ADOS as reported by Gotham et al. (J Autism Dev Disord 39: 693–705, 2009), was investigated in an independent sample of 1248 Dutch children with 1455 ADOS administrations (modules 1, 2 and 3). The greater comparability between ADOS administrations at different times, ages and in different modules, as reached by Gotham et al. with the calibrated severity measures, seems to be corroborated by the current study for module 1 and to a lesser extent for module 3. For module 2, the calibrated severity scores need to be further investigated within a sample that resembles Gotham’s sample in age and level of verbal functioning

Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits

Funder: H2020 European Research Council; doi: http://dx.doi.org/10.13039/100010663Funder: Research Foundation FlandersFunder: Universiteit Gent; doi: http://dx.doi.org/10.13039/501100004385Funder: Marguerite-Marie DelacroixFunder: Autistica; doi: http://dx.doi.org/10.13039/100011706Funder: Riksbankens Jubileumsfond; doi: http://dx.doi.org/10.13039/501100004472; Grant(s): NHS14-1802:1Funder: K.F. Hein FondsFunder: Scott Family Junior Research FellowshipAbstract: Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years

Gene-Network Analysis Identifies Susceptibility Genes Related to Glycobiology in Autism

The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD), and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD