Reelin Associated With Restricted and Stereotyped Behavior Based on Principal Component Analysis on Autism Diagnostic Interview-Revised

Tämä artikkeli ei ole avattavissa lehden sivuilta, koska linkit ja DOI vievät väärään artikkeliin samoin PDF sen ohessa. Kustantajalle ilmoitettu ja pyydetty korjausta.Abstract Background: Twin and family studies have indicated a strong genetic component in autism spectrum disorders, and genetic studies have revealed highly heterogeneous risk factors. The range and severity of the symptom presentation also vary in the spectrum. Thus, symptom-based phenotypes are putatively more closely related to the underlying biology of autism than the end-state diagnosis. Methods: We performed principal component analysis on Autism Diagnostic Interview-Revised algorithm for 117 Finnish families and 594 families from the Autism Genetic Research Exchange (AGRE). The resulting continuous component scores were used as quantitative phenotypes in family-based association analysis. In addition, K-means clustering was performed to cluster and visualize the results of the PCA. Unaffected siblings were included in the study. Results: The components were interpreted as Social Component (SC), communication component and Restricted and Stereotyped Behavior Component (RSBC). K-means clustering showed that, especially in SC, the range of the symptom severity was increased by the siblings. The association of neuroligin 1 with SC was increased, compared to a previous study where only the end-state diagnosis was used. In RSBC, the range of the symptom severity of siblings overlapped greatly with that of patients, which could explain why no association of reelin was found in previous studies in which only the end-state diagnosis was used, but a significant association of reelin with RSBC was now found in the Finnish families (Bonferroni-corrected p=0.029 for rs362644). Although, the Finnish sample is isolated and genetically very homogeneous, compared to the heterogeneous background of AGRE families, many single-nucleotide polymorphisms in reelin, showed modest association with RSBC in the AGRE sample, too. Conclusions: This study demonstrates how the quantitative phenotypes can affect the association analyses, and yields further support to the use of siblings in the study of complex neuropsychiatric disorders.Peer reviewe

On the autism spectrum?:recognition and assessment of quantitative autism traits in high-functioning school-aged children. An epidemiological and clinical study

Abstract Background: There is wide variability in the phenotypic manifestation of autism spectrum disorder (ASD). Recognizing autistic traits behind socio-emotional and adaptive problems in children with normal cognitive level can therefore be challenging. Aims and methods: The purpose of this study was to find tools for recognition of autism traits for clinicians working in primary/secondary settings. Two internationally used and empirically valid quantitative screeners, the Autism Spectrum Screening Questionnaire (ASSQ) and the Social Responsiveness Scale (SRS), were translated into Finnish and evaluated among high-functioning elementary school-aged children. An epidemiological target population of 8-year-old children (N=4,408) including 28 children with ASD was rated by parents and teachers using the ASSQ in order to assess cut-off scores for the Finnish ASSQ, and sensory abnormalities (SA) were determined in order to estimate the prevalence of SAs, and to investigate associations between sensory-perceptual problems and quantitative autism traits (QAT). The SRS was evaluated in a clinical ASD case (N=44)-control (N=44) study. It was also studied whether QAT of family members were associated with child QAT using the SRS. Results: Collecting parent and teacher ASSQ ratings and a cut-off of summed 30 points are recommended for ASD diagnostic assessments. The Finnish SRS was able to differentiate children with ASD from a normative child sample. The prevalence of SAs was 8% in the general population and 54% in the ASD sample. Tactile, auditory and olfactory hypersensitivities were associated with an elevated risk for an ASD diagnosis and auditory hypersensitivity explained the variance in the ASSQ scores among the ASD sample. In the normative sample, mother-child SRS QAT were more strongly associated, whereas in the ASD sample, a stronger positive correlation was found between father and child SRS QAT. Conclusions: In ASSQ screening, it is essential to collect both parent and teacher assessments. The SRS offers valuable information for determining the focal points of rehabilitation and evaluating treatment outcome. The SAs of the child as well as high QAT levels of male family members are indicators of an elevated risk for ASD.Tiivistelmä Tausta: Autismikirjon häiriön kliininen oirekuva vaihtelee henkilöstä toiseen. Tästä johtuen autististen piirteiden tunnistaminen lapsen sosioemotionaalisten ja sopeutumisvaikeuksien taustalta voi olla haasteellista. Tavoitteet ja menetelmät: Tutkimuksen tarkoituksena oli etsiä kognitiivisesti hyvätasoisten peruskouluikäisten parissa työskenteleville kliinikoille apukeinoja autististen piirteiden tunnistamiseen. Kaksi kansainvälisesti käytettyä seulontamittaria, Autismikirjon seulontalomake (ASSQ) ja Sosiaalisen vastavuoroisuuden arviointiasteikko (SRS), käännettiin suomeksi ja niiden psykometrisiä ominaisuuksia arvioitiin. Lisäksi tutkittiin, olivatko aistipoikkeavuudet tai vanhempien autistismipiirteisyys yhteydessä peruskouluikäisen lapsen autismipiirteisyyteen. Vanhemmat ja opettaja täyttivät ASSQ:n 8-vuotiaista epidemiologisen kohderyhmän lapsista (N=4408), joista 28:lla oli autismikirjon häiriö, ja kohderyhmän lasten aistipoikkeavuudet kartoitettiin. ASSQ:n seulontarajat sekä aistipoikkeavuuksien esiintyvyys ja yhteys autismipiirteisyyteen määritettiin. SRS evaluoitiin ja perheen sisäisen autismipiirteisyyden vertailu tehtiin kliinisessä autismikirjo (N=44)-verrokki (N=44)-aineistossa. Tulokset: Vanhempien ja opettajan ASSQ-arviointien yhteenlaskettu pistemäärä 30 oli parhaiten toimiva seulontaraja autismikirjon häiriön diagnostisia tutkimuksia varten. SRS erotteli autismikirjon lapset normiaineistosta. Aistipoikkeavuuksien esiintyvyys kokonaisväestössä oli 8 % ja autismikirjon lapsilla 54 %. Tunto-, kuulo- ja hajuyliherkkyys olivat yhteydessä kohonneeseen autismikirjon häiriön riskiin ja kuuloyliherkkyys selitti autismipiirteisyyden vaihtelua autismikirjon lapsilla. Normiaineistossa lapsen ja äidin autismipiirteisyys olivat vahvemmin yhteydessä toisiinsa, kun taas autismikirjon lasten perheissä lapsen ja isän autismipiirteisyys olivat vahvemmin yhteydessä toisiinsa. Päätelmät: ASSQ-arvioinnissa on ensiarvoisen tärkeää kerätä tietoa lapsen käyttäytymisestä sekä koti- että kouluympäristöstä. SRS on käyttökelpoinen määriteltäessä kuntoutuksen painopistealueita ja kartoitettaessa sen vaikuttavuutta. Lapsen aistipoikkeavuudet sekä hänen miespuolisten perheenjäsentensä vahva autismipiirteisyys viittaavat autismikirjon häiriön mahdollisuuteen

Co-activation pattern alterations in autism spectrum disorder:a volume-wise hierarchical clustering fMRI study

Abstract Introduction: There has been a growing effort to characterize the time-varying functional connectivity of resting state (RS) fMRI brain networks (RSNs). Although voxel-wise connectivity studies have examined different sliding window lengths, nonsequential volume-wise approaches have been less common. Methods: Inspired by earlier co-activation pattern (CAP) studies, we applied hierarchical clustering (HC) to classify the image volumes of the RS-fMRI data on 28 adolescents with autism spectrum disorder (ASD) and their 27 typically developing (TD) controls. We compared the distribution of the ASD and TD groups‘ volumes in CAPs as well as their voxel-wise means. For simplification purposes, we conducted a group independent component analysis to extract 14 major RSNs. The RSNs' average z-scores enabled us to meaningfully regroup the RSNs and estimate the percentage of voxels within each RSN for which there was a significant group difference. These results were jointly interpreted to find global group-specific patterns. Results: We found similar brain state proportions in 58 CAPs (clustering interval from 2 to 30). However, in many CAPs, the voxel-wise means differed significantly within a matrix of 14 RSNs. The rest-activated default mode-positive and default mode-negative brain state properties vary considerably in both groups over time. This division was seen clearly when the volumes were partitioned into two CAPs and then further examined along the HC dendrogram of the diversifying brain CAPs. The ASD group network activations followed a more heterogeneous distribution and some networks maintained higher baselines; throughout the brain deactivation state, the ASD participants had reduced deactivation in 12/14 networks. During default mode-negative CAPs, the ASD group showed simultaneous visual network and either dorsal attention or default mode network overactivation. Conclusion: Nonsequential volume gathering into CAPs and the comparison of voxel-wise signal changes provide a complementary perspective to connectivity and an alternative to sliding window analysis

Attention and Working Memory in Adolescents with Autism Spectrum Disorder : A Functional MRI Study

The present study examined attention and memory load-dependent differences in the brain activation and deactivation patterns between adolescents with autism spectrum disorders (ASDs) and typically developing (TD) controls using functional magnetic resonance imaging. Attentional (0-back) and working memory (WM; 2-back) processing and load differences (0 vs. 2-back) were analysed. WM-related areas activated and default mode network deactivated normally in ASDs as a function of task load. ASDs performed the attentional 0-back task similarly to TD controls but showed increased deactivation in cerebellum and right temporal cortical areas and weaker activation in other cerebellar areas. Increasing task load resulted in multiple responses in ASDs compared to TD and in inadequate modulation of brain activity in right insula, primary somatosensory, motor and auditory cortices. The changes during attentional task may reflect compensatory mechanisms enabling normal behavioral performance. The inadequate memory load-dependent modulation of activity suggests diminished compensatory potential in ASD.Peer reviewe

Non-linguistic comprehension, social inference and empathizing skills in autistic young adults, young adults with autistic traits and control young adults:group differences and interrelatedness of skills

Abstract Background: Despite increasing knowledge of social communication skills of autistic peole, the interrelatedness of different skills such as non-linguistic comprehension, social inference and empathizing skills is not much known about. A better understanding of the complex interplay between different domains of social communication helps us to develop assessment protocols for individuals with social communication difficulties. Aims: To compare the performances of autistic young adults, young adults with autistic traits identified in childhood and control young adults in social communication tasks measuring non-linguistic comprehension, social inference and empathizing skills. In addition, to examine associations between the different social communication measures. Methods & Procedures: Autistic young adults (n = 34), young adults with autistic traits (n = 19) and control young adults (n = 36) completed the extra- and paralinguistic scales of the Assessment Battery for Communication (ABaCo), the Faux Pas Recognition Test, Social–Pragmatic Questions (SoPra) and the Empathy Quotient (EQ). Outcomes & Results: Group differences were found in the performance in the ABaCo, SoPra and EQ scores. Compared with the control young adults, autistic young adults scored lower. The performance of the young adults in the autistic traits group fell in between the other two groups. There were no group differences in the Faux Pas Recognition Test. The variability within the groups was large in all measurements. In the control group, there was a significant correlation between EQ and SoPra scores and between the Faux Pas and SoPra scores. In the autistic group, a significant correlation was found between Faux Pas and SoPra scores. Also, other patterns were observed but these were not statistically significant. Conclusions & Implications: The young adults with autistic traits fell in between the control and autistic young adults, highlighting the presence of the continuum in the terms of features of social communication. The results support other current research that suggests that theory of mind and other social communication skills may not be universally or widely impaired in all autistic individuals without cognitive deficits. Although all tasks examined social communication skills, only a small number of significant correlations were found between test scores. This highlights that clinical conclusions about a person’s social communication should be based on the outcomes of different types of methods measuring different aspects of social communication. It is clear that the interrelatedness of different social communication skills needs further research. What This Paper Adds What is already known on this subject: For successful communication, the ability to infer others’ emotions, intentions and mental states is crucial. Autistic people have difficulty with many aspects of social communication. However, the associations between different aspects of social communication need to be better understood. What this paper adds to existing knowledge: The unique contribution of this study is to compare the performance of autistic people not only with that of a control group but also with people with childhood autistic traits. This provides an understanding of the interrelatedness of different social communication skills in people with varying degrees of autistic traits. This study used four assessment methods focusing on three different social communication elements (non-linguistic comprehension, social inference and empathizing skills). These elements have complex relationships to one another, some being closely overlapping, some more distally related and some reflect more complex multifactorial elements. This study shows that although groups differ from each other in most of the assessments, the performance of different groups overlapped showing that many autistic young adults can perform well in non-linguistic and social inference tasks in structured assessment contexts. What are the potential or actual clinical implications of this work? Our findings suggest that in the assessment of social communication, self-reports and clinical assessments can be used effectively together. They can complement each other, pointing out the strengths and weaknesses of a person, leading to more personalized therapeutic interventions