scholarly journals Rare variants in the outcome of social skills group training for autism

2021 ◽  
Author(s):  
Danyang Li ◽  
Nora Choque Olsson ◽  
Martin Becker ◽  
Abishek Arora ◽  
Hong Jiao ◽  
...  
2021 ◽  
Author(s):  
Danyang Li ◽  
Nora Choque Olsson ◽  
Martin Becker ◽  
Abishek Arora ◽  
Hong Jiao ◽  
...  

Background Exome sequencing has been proposed as the first-tier genetic testing in autism spectrum disorder (ASD). Here, we performed exome sequencing in autistic individuals with average to high intellectual abilities (N = 207) to identify a molecular diagnosis of ASD and genetic modulators of intervention outcomes following social skills group training (SSGT) or standard care. Methods Within a randomized controlled trial of SSGT, we performed exome sequencing to prioritize variants of clinical significance (VCSs), variants of uncertain significance (VUSs) and generated a pilot scheme to calculate genetic scores representing the genetic load of rare and common variants in the synaptic transmission pathway (GSSyTr and GSSyTc). The association with the primary outcomes (parent-reported autistic traits, Social Responsiveness Scale) was computed using a mixed linear model. Behavioral and genetic features were combined in a machine learning (ML) model to predict the individual response within the cohort. Results In total, 4.4% (n = 9) and 11.3% (n = 23) of the cohort carried VCSs and VUSs, respectively. Compared to non-carriers, individuals with VCS or VUS together tended to have limited improvements of the interventions (β = 9.22; CI (-0.25, 18.70); P = 0.057) and improved significantly less from standard care (β = 9.35; CI (0.70, 18.00); P = 0.036), but not from SSGT (β = -2.50; CI (-13.34, 8.35); P = 0.65). In addition, both GSSyTr and GSSyTc were associated with differential outcomes in standard care and SSGT groups. Our ML model showed the importance of rare variants for outcome prediction. Conclusions Autistic individuals with likely pathogenic rare variants identified by exome sequencing might benefit less from the standard care. SSGT could therefore be of heightened importance for this subgroup. Further studies are needed to understand genetic predisposition to intervention outcomes.


Autism ◽  
2016 ◽  
Vol 20 (8) ◽  
pp. 995-1010 ◽  
Author(s):  
Nora Choque Olsson ◽  
Daniel Rautio ◽  
Jenny Asztalos ◽  
Ulrich Stoetzer ◽  
Sven Bölte

2019 ◽  
Author(s):  
Danyang Li ◽  
Nora Choque-Olsson ◽  
Hong Jiao ◽  
Nina Norgren ◽  
Ulf Jonsson ◽  
...  

AbstractSocial skills group training (SSGT) is one of the most frequently used behavior interventions in children and adolescents with autism spectrum disorder (ASD). Current evidence suggests that the effects are moderate and heterogeneous. Genetic predisposition could be one of the factors contributing to this heterogeneity. Therefore, we used polygenic risk score (PRS) and gene-set analysis to investigate the association between SSGT response and common variants in autistic individuals. Participants from the largest randomized clinical trial of SSGT in ASD to date were selected for genotyping. Polygenic risk scores (PRSs) for ASD, attention deficit hyperactivity disorder (ADHD), and educational attainment (EA) were calculated, and their associations with the intervention outcome at post-intervention and follow-up were tested using mixed linear model. In addition, thirty-two gene sets within five categories (synaptic, glial, FMRP, glutamate, and mitochondrial) were selected to evaluate their role in the intervention outcome. Individuals with higher PRSs for ASD and ADHD had inferior response after SSGT. After multiple test correction, significant results were kept for higher ADHD PRS at follow-up (β = 6.67, p = 0.016). Five gene sets within synaptic category showed modest association with reduced response to SSGT in ASD. Taken together, we provided preliminary evidence that genetic liability calculated using PRS and common variants in synapse gene sets could influence the outcome of SSGT. Our results hold promise for future research into the genetic contribution to individual response to ASD interventions, and should be validated in larger cohorts.


2018 ◽  
Vol 28 (3) ◽  
pp. 415-424 ◽  
Author(s):  
Vera Dekker ◽  
Maaike H. Nauta ◽  
Marieke E. Timmerman ◽  
Erik J. Mulder ◽  
Lianne van der Veen-Mulders ◽  
...  

2021 ◽  
pp. 025371762110241
Author(s):  
Priyadarshini Aruldass ◽  
Thamarai Selvi Sekar ◽  
Srikrithika Saravanan ◽  
Reema Samuel ◽  
K. S. Jacob

Background: The study aimed to evaluate the effectiveness of a social skills training program provided at the occupational therapy unit of a tertiary care center in India. Methods: The study used a pre–post interventional design where 101 consecutive patients with a diagnosis of schizophrenia or bipolar affective disorder, between 18 and 60 years, who provided written informed consent, were assessed on the Vellore Assessment of Social Performance (VASP) during the first week of attendance (baseline). Subsequently, they were enrolled in a six-session social skills group training program for two weeks. They were assessed on the VASP after one week (midterm assessment) and at the end (posttest) of the intervention. A follow-up assessment was done two weeks after cessation of the intervention. The participants were also scored on the Brief Psychiatric Rating Scale (BPRS) at four time points. Results: Repeated measures ANOVA revealed significant differences in the VASP scores between time points, that is, F(baseline, midterm) = −4.34 and P = 0.001; F (baseline, postgroup) = −6.92 and P = 0.001; and F (baseline, follow-up) = −8.71 and P = 0.001. The correlation between the BPRS and VASP scores was also significant at each time point. Conclusion: The social skills group training protocol seems to be effective and feasible for the Indian population. Since conducting multicenter clinical trials might not always be possible in resource-constrained settings, this study might be considered preliminary evidence for context-specific, peer-/family-supported social skills training.


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