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- Bang, Peter, 1992-
(författare)
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Beyond Categories : A Dimensional Approach to Autism and Sensorimotor Differences
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Autism spectrum conditions (ASC) encompass a range of sensory, motor, and social-communicative differences, reflecting the considerable heterogeneity within the autism spectrum. This diversity underscores the limitations of categorical diagnostic approaches, which often fail to capture the individualized manifestations of autism. Advances in genetics and neuroscience have driven a shift towards dimensional frameworks that emphasize the spectrum nature of autism and the broad autism phenotype (BAP). BAP encapsulates subclinical traits that mirror those of autism in the general population, challenging the conventional boundaries between clinical and non-clinical populations. Furthermore, sensorimotor differences, which are particularly prevalent in individuals with ASC, follow a spectrum-like pattern similar to the BAP and are predictive of developmental outcomes related to social participation, communication, and overall quality of life in people with and without ASC. However, specific descriptions of these relationships are lacking.This dissertation investigated the complex relationships between sensorimotor differences and autistic traits (ATs). Through a series of five interconnected studies, we examined broad sensory processing patterns and specific sensory modalities, namely auditory processing and motor/proprioception, to explore their roles in autistic phenotypes.Study 1 of the dissertation validated a Swedish translation of the Broad Autism Phenotype Questionnaire (BAPQ). By examining parents' BAP traits, the study highlighted significant associations between higher ATs and having a child with ASC. Furthermore, it confirmed the presence of all three AT domains—social interaction (ATSOC), communication (ATCOM), and cognitive rigidity (ATRIG), reinforcing the genetic and phenotypic continuity between clinical and subclinical ATs.Study 2 and Study 3 served as broader investigations into all seven sensory modalities and their associations with ATs. Study 2 explored these modality-specific associations, using Bayesian stochastic search variable selection (SSVS) and dominance analysis. This study highlighted auditory processing difficulties as the most consistent predictor of all three AT domains. Additionally, proprioceptive and tactile processing difficulties were specifically associated with ATCOM and ATSOC, respectively.Study 3 extended this analysis to a developing population, focusing on the relationship between sensorimotor processing, ATs, and anxiety in children aged 6-11 years. Identical to Study 2, we found tactile symptoms as a predictor of ATSOC, proprioceptive symptoms for ATCOM, and auditory symptoms for ATRIG. In addition, olfactory symptoms were selected as a predictor of ATCOM, and motor coordination was a consistent predictor of all AT domains. Using SSVS, this study also identified that auditory and olfactory processing difficulties were strong predictors of anxiety symptoms.Building on the previous studies, Study 4 narrowed the focus to auditory processing differences, investigating specific auditory problems and their associations with the AT domains. All AT domains significantly predicted affective reactions to sounds, while difficulties with speech perception, spatial perception, and auditory stream segregation were most strongly predicted by ATCOM.Study 5 focused on the previously found links between motor coordination and proprioceptive processing and ATCOM. Using causal mediation analysis within a counterfactual framework, this study found that cerebellar error correction deficits, measured through a finger tapping task, significantly impacted ATCOM through motor skills in childhood.Together, this dissertation provides a comprehensive overview of the sensory processing dimensions related to the core AT domains. Specifically, the studies underscored the clinical significance of monitoring auditory and olfactory complaints in children, as these were predictive of anxiety, and emphasized that early motor deficits impact social communication development. The findings advocate for the inclusion of detailed sensory and motor assessments in neurodevelopmental evaluations to identify children at risk for poor mental health outcomes. Future research should continue to explore the mechanisms underlying sensory processing differences. Particular focus should be placed on auditory and motor/proprioceptive functions and their contributions to ATs and clinical outcomes, such as anxiety. Emphasis should also be given to longitudinal studies that track these relationships over time.
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| 2. |
- Charman, Tony, et al.
(författare)
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The EU-AIMS Longitudinal European Autism Project (LEAP) : clinical characterisation.
- 2017
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers.METHODS: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms.RESULTS: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females.CONCLUSIONS: The established phenotypic heterogeneity in ASD is well captured in the LEAP cohort. Variation both in core ASD symptom severity and in commonly co-occurring psychiatric symptoms were systematically associated with sex, age and IQ. The pattern of ASD symptom differences with age and sex also varied by whether these were clinician ratings or parent- or self-reported which has important implications for establishing stratification biomarkers and for their potential use as outcome measures in clinical trials.
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| 3. |
- Loth, Eva, et al.
(författare)
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The EU-AIMS Longitudinal European Autism Project (LEAP) : design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders.
- 2017
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD.METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability.RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted).CONCLUSION: We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies.
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