Co-occurring medical disorders and associated physiological abnormalities in individuals with autism spectrum disorder (ASD) may provide insight into causal pathways or underlying biological ...mechanisms. Here, we review medical conditions that have been repeatedly highlighted as sharing the strongest associations with ASD-epilepsy, sleep, as well as gastrointestinal and immune functioning. We describe within each condition their prevalence, associations with behavior, and evidence for successful treatment. We additionally discuss research aiming to uncover potential aetiological mechanisms. We then consider the potential interaction between each group of conditions and ASD and, based on the available evidence, propose a model that integrates these medical comorbidities in relation to potential shared aetiological mechanisms. Future research should aim to systematically examine the interactions between these physiological systems, rather than considering these in isolation, using robust and sensitive biomarkers across an individual's development. A consideration of the overlap between medical conditions and ASD may aid in defining biological subtypes within ASD and in the development of specific targeted interventions.
To evaluate which early neurocognitive and behavioral precursors are associated with the development of attention-deficit/hyperactivity disorder (ADHD) and whether these are currently targeted in ...early interventions.
We conducted 2 systematic reviews and meta-analyses of empirical studies to examine the following: (1) early-life (0-5 years) neurocognitive and behavioral precursors associated with familial likelihood for ADHD, an early ADHD diagnosis/elevated ADHD symptoms, and/or the presence of later-childhood ADHD; and (2) interventions delivered to children aged 0 to 5 years targeting the identified precursors or measuring these as outcomes. Standardized mean differences (Hedges' g) and pre-post-treatment change scores (SMD) were computed.
A total of 149 studies (165,095 participants) investigating 8 neurocognitive and behavioral domains met inclusion criteria for part 1. Multi-level random-effects meta-analyses on 136 studies revealed significant associations between ADHD and poorer cognitive (g = -0.46 95% CIs: -0.59, -0.33), motor (g = -0.35 CIs: -0.48, -0.21) and language (g = -0.43 CIs: -0.66, -0.19) development, social (g = 0.23 CIs: 0.03, 0.43) and emotional (g = 0.46 CIs: 0.33, 0.58) difficulties, early regulatory (g = 0.30 CIs: 0.18, 0.43) and sleep (g = 0.29 CIs: 0.14, 0.44) problems, sensory atypicalities (g = 0.52 CIs: 0.16, 0.88), elevated activity levels (g = 0.54 CIs: 0.37, 0.72), and executive function difficulties (g = 0.34 CIs: 0.05, 0.64 to -0.87 CIs: -1.35, -0.40). A total of 32 trials (28 randomized, 4 nonrandomized, 3,848 participants) testing early interventions that targeted the identified precursors met inclusion criteria for part 2. Multi-level random-effects meta-analyses on 22 studies revealed significant intervention-related improvements in ADHD symptoms (SMD = 0.43 CIs: 0.22, 0.64) and working memory (SMD = 0.37 CIs: 0.06, 0.69).
Children aged 0 to 5 years with current or later-emerging ADHD are likely to experience difficulties in multiple neurocognitive/behavioral functions. Early interventions show some effectiveness in reducing ADHD symptoms, but their effects on neurocognitive/behavioral difficulties require further study.
We investigated key event-related brain potential markers (ERPs) derived from a flanked continuous performance task (CPT) and whether these would show phenotypic associations with ADHD ...(attention-deficit/hyperactivity disorder) in a population-based sample. We further explored whether there was preliminary evidence that such ERPs could also index genetic risk for ADHD (depending on finding phenotypic associations). Sixty-seven male-only twin pairs (N = 134; aged 12-15) from a subsample of the Twins' Early Development Study, concordant and discordant for ADHD symptoms, performed the flanked CPT (or CPT-OX) while electroencephalography (EEG) was recorded. ERPs were obtained for cue (P3, CNV or contingency negative variation), go (P3, N2) and nogo trials (P3, N2). We found no phenotypic associations between CPT-derived ERPs and ADHD-the sizes of the estimated phenotypic correlations were nonsignificant and very small (r's = -.11 to .04). Twin-model fitting analyses using structural equation modelling provided preliminary evidence that some of the ERPs were heritable (with the most robust effect for go-P3 latency), but there was limited evidence of any genetic associations between ERPs and ADHD, although with the caveat that our sample was small and hence had limited power. Overall, unlike in previous research, there was no evidence of phenotypic (nor preliminary evidence for genetic) associations between ADHD and CPT-derived ERPs in this study. Hence, it may be currently premature for genetic analyses of ADHD to be guided by CPT-derived ERP parameters (unlike alternative cognitive-neurophysiological approaches which may be more promising). Further research with better-powered, population-based, genetically-informative and cross-disorder samples are required, which could be facilitated by emerging mobile EEG technologies.
Atypicalities in perception and interpretation of faces and emotional facial expressions have been reported in both autism and attention-deficit/hyperactivity disorder (ADHD) during childhood and ...adulthood. Investigation of face processing during young adulthood (18 to 25 years), a transition period to full-fledged adulthood, could provide important information on the adult outcomes of autism and ADHD.
In this study, we investigated event-related potentials (ERPs) related to visual face processing in autism, ADHD, and co-occurring autism and ADHD in a large sample of young adults (
= 566). The groups were based on the Diagnostic Interview for ADHD in Adults 2.0 (DIVA-2) and the Autism Diagnostic Observation Schedule-2 (ADOS-2). We analyzed ERPs from two passive viewing tasks previously used in childhood investigations: (1) upright and inverted faces with direct or averted gaze; (2) faces expressing different emotions.
Across both tasks, we consistently found lower amplitude and longer latency of N170 in participants with autism compared to those without. Longer P1 latencies and smaller P3 amplitudes in response to emotional expressions and longer P3 latencies for upright faces were also characteristic to the autistic group. Those with ADHD had longer N170 latencies, specific to the face-gaze task. Individuals with both autism and ADHD showed additional alterations in gaze modulation and a lack of the face inversion effect indexed by a delayed N170.
Alterations in N170 for autistic young adults is largely consistent with studies on autistic adults, and some studies in autistic children. These findings suggest that there are identifiable and measurable socio-functional atypicalities in young adults with autism.
While it is important to determine global prevalence rates to understand the impact of geographic, cultural/ethnic and socioeconomic factors, inequalities in the clinical identification and diagnosis ...of TAND is well recognised because of marked differences in the nature of health care systems and diagnostic practices between countries (including utilisation of different diagnostic nosological systems which have evolved over time).' (3) Operational criteria for assigning a diagnosis of ASD and ADHD are not provided in the TAND Checklist, and inter-rater reliability for assigning diagnoses has not been reported in the TOSCA study. ...the patients attended a wide range of different types of clinics (genetic, paediatric, epilepsy, etc.,) that were led by specialists from many different disciplines with variable levels of expertise in clinically recognising and diagnosing TAND. ...different thresholds for diagnosis of ASD and ADHD traits make it challenging to determine true prevalence; 4. By contrast, complex psychopathologies such as ASD and ADHD where diagnostic tools and operational criteria are increasingly recognised as necessary aids to clinical diagnosis, show quite significant differences in prevalence estimates between studies. ...the findings from the TS 2000 study regarding the prevalence of definite and probable ASD and ADHD demonstrate how sensitive estimates are to variations in where the threshold for diagnosis is placed, when dealing with dimensionally distributed traits.
Autism Spectrum Disorder (ASD) is a behavioral syndrome caused by complex genetic and non-genetic risk factors. It has been proposed that these risk factors lead to alterations in the development and ...'wiring' of brain circuits and hence, the emergence of ASD. Although several lines of research lend support to this theory, etiological and clinical heterogeneity, methodological issues and inconsistent findings have led to significant doubts. One of the best established, albeit rare, causes of ASD is the genetic condition Tuberous Sclerosis Complex (TSC), where 40% of individuals develop ASD. A recent study by Peters and Taquet et al. analyzed electroencephalography (EEG) data using graph theory to model neural 'connectivity' in individuals with TSC with and without ASD and cases with 'idiopathic' ASD. TSC cases exhibited global under-connectivity and abnormal network topology, whereas individuals with TSC + ASD demonstrated similar connectivity patterns to those seen in individuals with idiopathic ASD: decreased long- over short-range connectivity. The similarity in connectivity abnormalities in TSC + ASD and ASD suggest a common final pathway and provide further support for 'mis-wired' neural circuitry in ASD. The origins of the connectivity changes, and their role in mediating between the neural and the cognitive/behavioral manifestations, will require further study.Please see related research article here http://www.biomedcentral.com/1741-7015/11/54.
Early difficulties in engaging attentive brain states in social settings could affect learning and have cascading effects on social development. We investigated this possibility using multichannel ...electroencephalography during a face/non-face paradigm in 8-month-old infants with (FH, n = 91) and without (noFH, n = 40) a family history of autism spectrum disorder (ASD). An event-related potential component reflecting attention engagement, the Nc, was compared between FH infants who received a diagnosis of ASD at 3 years of age (FH-ASD; n = 19), FH infants who did not (FH-noASD; n = 72) and noFH infants (who also did not, hereafter noFH-noASD; n = 40). 'Prototypical' microstates during social attention were extracted from the noFH-noASD group and examined in relation to later categorical and dimensional outcome. Machine-learning was used to identify the microstate features that best predicted ASD and social adaptive skills at three years. Results suggested that whilst measures of brain state timing were related to categorical ASD outcome, brain state strength was related to dimensional measures of social functioning. Specifically, the FH-ASD group showed shorter Nc latency relative to other groups, and duration of the attentive microstate responses to faces was informative for categorical outcome prediction. Reduced Nc amplitude difference between faces with direct gaze and a non-social control stimulus and strength of the attentive microstate to faces contributed to the prediction of dimensional variation in social skills. Taken together, this provides consistent evidence that atypical attention engagement precedes the emergence of difficulties in socialization and indicates that using the spatio-temporal characteristics of whole-brain activation to define brain states in infancy provides an important new approach to understanding of the neurodevelopmental mechanisms that lead to ASD.
The Coronavirus disease 2019 (COVID-19) pandemic has impacted parental and child mental health and wellbeing in the UK. This study aimed to explore the experiences of parents of children with rare ...neurological and neurodevelopmental conditions with a known or suspected genetic cause (neurogenetic) across the first year of the pandemic in the UK.
Semi-structured interviews were conducted with 11 parents of children with rare neurogenetic conditions. Parents were recruited via opportunity sampling from the CoIN Study, a longitudinal quantitative study exploring the impact of the pandemic on the mental health and wellbeing of families with rare neurogenetic conditions. Interviews were analysed using Interpretative Phenomenological Analysis.
Four main themes were identified: (1) "A varied impact on child wellbeing: from detrimental to 'no big drama'"; (2) "Parental mental health and wellbeing: impact, changes, and coping"; (3) "'The world had shut its doors and that was that': care and social services during the pandemic"; and (4) "Time and luck: abstract concepts central to parents' perspectives of how they coped during the pandemic". The majority of parents described experiencing an exacerbation of pre-pandemic challenges due to increased uncertainty and a lack of support, with a minority reporting positive effects of the pandemic on family wellbeing.
These findings offer a unique insight into the experiences parents of children with rare neurogenetic conditions across the first year of the pandemic in the UK. They highlight that the experiences of parents were not pandemic-specific, and will continue to be highly relevant in a non-pandemic context. Future support should to be tailored to the needs of families and implemented across diverse future scenarios to promote coping and positive wellbeing.
•Density and cross-section of specific white matter fibres is reduced in TSC.•Right SLF-I is implicated in autism spectrum symptoms in TSC.•Bilateral ILF is implicated in ADHD symptoms in ...TSC.•Fixel-based analysis is a useful tool to evaluate white matter changes in TSC.•White matter changes may underlie neurodevelopmental disorder in TSC.
Tuberous sclerosis complex is a rare genetic multisystem condition that is associated with a high prevalence of neurodevelopmental disorders such as autism and attention-deficit/hyperactivity disorder. The underlying neural mechanisms of the emergence of these symptom domains in tuberous sclerosis complex remain unclear.
Here, we use fixel-based analysis of diffusion-weighted imaging, which allows for the differentiation between multiple fibre populations within a voxel, to compare white matter properties in 16 participants with tuberous sclerosis complex (aged 11–19) and 12 age and sex matched control participants. We further tested associations between white matter alterations and autism and inattention symptoms as well as cognitive ability in participants with tuberous sclerosis complex.
Compared to controls, participants with tuberous sclerosis complex showed reduced fibre density cross-section (FDC) in the dorsal branch of right superior longitudinal fasciculus and bilateral inferior longitudinal fasciculus, reduced fibre density (FD) in bilateral tapetum, and reduced fibre cross-section (FC) in the ventral branch of right superior longitudinal fasciculus. In participants with tuberous sclerosis complex, the extent of FDC reductions in right superior longitudinal fasciculus was significantly associated with autism traits (social communication difficulties and restricted, repetitive behaviours), whereas FDC reductions in right inferior longitudinal fasciculus were associated with inattention. The observed white matter alterations were unrelated to cognitive ability.
Our findings shed light on the fibre-specific biophysical properties of white matter alterations in tuberous sclerosis complex and suggest that these regional changes are selectively associated with the severity of neurodevelopmental symptoms.
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