Browsing by Author "Anagnostou, Evdokia"

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    Harmonizing two measures of adaptive functioning using computational approaches: prediction of vineland adaptive behavior scales II (VABS-II) from the adaptive behavior assessment system II (ABAS-II) scores
    (2024-12-03) Smith, Corinna; Lautarescu, Alexandra; Charman, Tony; Crosbie, Jennifer; Schachar, Russell J.; Iaboni, Alana; Georgiades, Stelios; Nicolson, Robert; Kelley, Elizabeth; Ayub, Muhammad; Jones, Jessica; Arnold, Paul D.; Lerch, Jason P.; Anagnostou, Evdokia; Kushki, Azadeh
    Abstract Background Very large sample sizes are often needed to capture heterogeneity in autism, necessitating data sharing across multiple studies with diverse assessment instruments. In these cases, data harmonization can be a critical tool for deriving a single dataset for analysis. This can be done through computational approaches that enable the conversion of scores across various instruments. To this end, our study examined the use of analytical approaches for mapping scores on two measures of adaptive functioning, namely predicting the scores on the vineland adaptive behavior scales II (VABS) from the scores on the adaptive behavior assessment system II (ABAS). Methods Data from the province of Ontario neurodevelopmental disorders network were used. The dataset included scores VABS and the ABAS for 720 participants (autism n = 547, 433 male, age: 11.31 ± 3.63 years; neurotypical n = 173, 95 male, age: 12.53 ± 4.05 years). Six regression approaches (ordinary least squares (OLS) linear regression, ridge regression, ElasticNet, LASSO, AdaBoost, random forest) were used to predict VABS total scores from the ABAS scores, demographic variables (age, sex), and phenotypic measures (diagnosis; core and co-occurring features; IQ; internalizing and externalizing symptoms). Results The VABS scores were significantly higher than the ABAS scores in the autism group, but not the neurotypical group (median difference: 8, 95% CI = (7,9)). The difference was negatively associated with age (beta = -1.2 ± 0.12, t = -10.6, p < 0.0001). All estimators demonstrated similar performance, with no statistically significant differences in mean absolute error (MAE) values across estimators (MAE range: 4.96–6.91). The highest contributing features to the prediction model were ABAS composite score, diagnosis, and age. Limitations This study has several strengths, including the large sample. We did not examine the conversion of domain scores across the two measures of adaptive functioning and suggest this as a future area of investigation. Conclusion Overall, our results supported the feasibility of harmonization. Our results suggest that a linear regression model trained on the ABAS composite score, the ABAS raw domain scores, and age, sex, and diagnosis would provide an acceptable trade-off between accuracy, parsimony, and data collection and processing complexity.
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    Magnetoencephalographic (MEG) brain activity during a mental flexibility task suggests some shared neurobiology in children with neurodevelopmental disorders
    (2019-08-19) Mogadam, Alexandra; Keller, Anne E; Arnold, Paul D; Schachar, Russell; Lerch, Jason P; Anagnostou, Evdokia; Pang, Elizabeth W
    Abstract Background Children with neurodevelopmental disorders (NDDs) exhibit a shared phenotype that involves executive dysfunctions including impairments in mental flexibility (MF). It is of interest to understand if this phenotype stems from some shared neurobiology. Methods To investigate this possibility, we used magnetoencephalography (MEG) neuroimaging to compare brain activity in children (n = 88; 8–15 years) with autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), as they completed a set-shifting/mental flexibility task. Results Neuroimaging results revealed a similar parietal activation profile across the NDD, groups suggesting a link to their shared phenotype. Differences in frontal activity differentiated the three clinical groups. Brain-behaviour analyses showed a link with repetitive behaviours suggesting shared dysfunction in the associative loop of the corticostriatal system. Conclusion Our study supports the notion that NDDs may exist along a complex phenotypic/biological continuum. All NDD groups showed a sustained parietal activity profile suggesting that they share a strong reliance on the posterior parietal cortices to complete the mental flexibility task; future studies could elucidate whether this is due to delayed brain development or compensatory functioning. The differences in frontal activity may play a role in differentiating the NDDs. The OCD group showed sustained prefrontal activity that may be reflective of hyperfrontality. The ASD group showed reduced frontal activation suggestive of frontal dysfunction and the ADHD group showed an extensive hypoactivity that included frontal and parietal regions. Brain-behaviour analyses showed a significant correlation with repetitive behaviours which may reflect dysfunction in the associative loop of the corticostriatal system, linked to inflexible behaviours.
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    Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation
    (2020-08-16) Goodman, Sarah J; Burton, Christie L; Butcher, Darci T; Siu, Michelle T; Lemire, Mathieu; Chater-Diehl, Eric; Turinsky, Andrei L; Brudno, Michael; Soreni, Noam; Rosenberg, David; Fitzgerald, Kate D; Hanna, Gregory L; Anagnostou, Evdokia; Arnold, Paul D; Crosbie, Jennifer; Schachar, Russell; Weksberg, Rosanna
    Abstract Background A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs). Methods We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4–18 years) using DNA extracted from saliva. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders. Results Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample. Conclusions Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders.