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"Ameis, Stephanie H."
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Coping, fostering resilience, and driving care innovation for autistic people and their families during the COVID-19 pandemic and beyond
by
Mulsant, Benoit H.
,
Szatmari, Peter
,
Ameis, Stephanie H.
in
Adaptation, Psychological
,
Anxiety
,
Autism
2020
The new coronavirus disease (COVID-19) pandemic is changing how society operates. Environmental changes, disrupted routines, and reduced access to services and social networks will have a unique impact on autistic individuals and their families and will contribute to significant deterioration in some. Access to support is crucial to address vulnerability factors, guide adjustments in home environments, and apply mitigation strategies to improve coping. The current crisis highlights that our regular care systems are not sufficient to meet the needs of the autism communities. In many parts of the world, people have shifted to online school and increased use of remote delivery of healthcare and autism supports. Access to these services needs to be increased to mitigate the negative impact of COVID-19 and future epidemics/pandemics. The rapid expansion in the use of telehealth platforms can have a positive impact on both care and research. It can help to address key priorities for the autism communities including long waitlists for assessment and care, access to services in remote locations, and restricted hours of service. However, system-level changes are urgently needed to ensure equitable access and flexible care models, especially for families and individuals who are socioeconomically disadvantaged. COVID-19 mandates the use of technology to support a broader range of care options and better meet the diverse needs of autistic people and their families. It behooves us to use this crisis as an opportunity to foster resilience not only for a given individual or their family, but also the system: to drive enduring and autism-friendly changes in healthcare, social systems, and the broader socio-ecological contexts.
Journal Article
Nabilone treatment for severe behavioral problems in adults with intellectual and developmental disabilities: Protocol for a phase I open-label clinical trial
2023
Severe behavioral problems (SBPs) are common contributors to morbidity and reduced quality of life for adults with intellectual and developmental disabilities (IDD) and their families. Current medications for SBPs show equivocal effectiveness and are associated with a high risk of side effects. New and safe treatments are urgently needed. While preliminary studies suggest that medical cannabinoids, particularly the synthetic cannabinoid nabilone, are plausible treatment options for SBPs in adults with IDD, data on the tolerability, safety and efficacy of nabilone in this population has never been investigated. Thus, we propose this first-ever Phase I pre-pilot open-label clinical trial to obtain preliminary data on the adherence, tolerability and safety profiles of nabilone in adults with IDD, and explore changes in SBPs pre- to post-treatment. We hypothesize that nabilone has favorable tolerability and safety profile for adults with IDD. The preliminary results will inform the next-stage pilot randomized controlled trials, followed by fully powered clinical trials eventually. This research helps fill the evidence gap in the use of cannabinoids in individuals with IDD to meet the needs of patients, families, and service providers.
Journal Article
Impaired Structural Connectivity of Socio-Emotional Circuits in Autism Spectrum Disorders: A Diffusion Tensor Imaging Study
2011
Abnormal white matter development may disrupt integration within neural circuits, causing particular impairments in higher-order behaviours. In autism spectrum disorders (ASDs), white matter alterations may contribute to characteristic deficits in complex socio-emotional and communication domains. Here, we used diffusion tensor imaging (DTI) and tract based spatial statistics (TBSS) to evaluate white matter microstructure in ASD.
DTI scans were acquired for 19 children and adolescents with ASD (∼8-18 years; mean 12.4±3.1) and 16 age and IQ matched controls (∼8-18 years; mean 12.3±3.6) on a 3T MRI system. DTI values for fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity, were measured. Age by group interactions for global and voxel-wise white matter indices were examined. Voxel-wise analyses comparing ASD with controls in: (i) the full cohort (ii), children only (≤12 yrs.), and (iii) adolescents only (>12 yrs.) were performed, followed by tract-specific comparisons. Significant age-by-group interactions on global DTI indices were found for all three diffusivity measures, but not for fractional anisotropy. Voxel-wise analyses revealed prominent diffusion measure differences in ASD children but not adolescents, when compared to healthy controls. Widespread increases in mean and radial diffusivity in ASD children were prominent in frontal white matter voxels. Follow-up tract-specific analyses highlighted disruption to pathways integrating frontal, temporal, and occipital structures involved in socio-emotional processing.
Our findings highlight disruption of neural circuitry in ASD, particularly in those white matter tracts that integrate the complex socio-emotional processing that is impaired in this disorder.
Journal Article
Assessing plasticity in the primary sensory cortex and its relation with atypical tactile reactivity in autism: A TMS-EEG protocol
2024
Atypical sensory reactivity is a cardinal presentation in autism. Within the tactile domain, atypical tactile reactivity (TR) is common, it emerges early, persists into adulthood, and impedes social interaction and daily functioning. Hence, atypical TR is a key target for biological intervention to improve outcomes. Brain mechanisms informing biological interventions for atypical TR remains elusive. We previously reported hyper-plasticity in the motor cortex in autistic adults and found that repetitive transcranial magnetic stimulation (rTMS), designed to strengthen inhibitory processes in the brain, reduced hyper-plasticity. Whether the primary sensory cortex (S1) is characterized by hyper-plasticity, which may underlie atypical TR in autism is unknown.
We aim to test whether hyper-plasticity in the S1 underlies atypical TR in autism, and investigate if a single session of rTMS can safely reduce hyper-plasticity in S1 in autistic adults.
Plasticity will be assessed in the left S1 with integrated paired associative stimulation and electroencephalography (PAS-EEG) paradigm in 32 autistic adults and 32 age-, sex-, and intelligence quotient-matched controls. Autistic participants will be further randomized (double-blind, 1:1) to receive a single-session of either sham or active 20 Hz bilateral rTMS over the S1 and the plasticity will be re-assessed over the left S1 on the same day.
Atypical TR has been identified as one of the top clinical research priorities that can influence outcome in autistic population. The study findings can be highly valuable to further elucidate the mechanism underlying atypical TR, which in turn can help with developing a mechanism-driven intervention.
Journal Article
Systematic comparisons of different quality control approaches applied to three large pediatric neuroimaging datasets
by
Nakua, Hajer
,
Joseph, Michael
,
Jacobs, Grace R.
in
Algorithms
,
Attention deficit hyperactivity disorder
,
Automation
2023
•Overall, there are differences in the participants excluded from four different quality control approaches across three pediatric datasets.•In clinically enriched samples, the greatest correspondence of excluded participants was between automated and visual quality control procedures.•Implementing quality control led to the exclusion of younger participants and those with greater clinical impairments.•Specific QC approach implemented did not lead to measurable differences in clinical or brain metric characteristics.
Poor quality T1-weighted brain scans systematically affect the calculation of brain measures. Removing the influence of such scans requires identifying and excluding scans with noise and artefacts through a quality control (QC) procedure. While QC is critical for brain imaging analyses, it is not yet clear whether different QC approaches lead to the exclusion of the same participants. Further, the removal of poor-quality scans may unintentionally introduce a sampling bias by excluding the subset of participants who are younger and/or feature greater clinical impairment. This study had two aims: (1) examine whether different QC approaches applied to T1-weighted scans would exclude the same participants, and (2) examine how exclusion of poor-quality scans impacts specific demographic, clinical and brain measure characteristics between excluded and included participants in three large pediatric neuroimaging samples.
We used T1-weighted, resting-state fMRI, demographic and clinical data from the Province of Ontario Neurodevelopmental Disorders network (Aim 1: n = 553, Aim 2: n = 465), the Healthy Brain Network (Aim 1: n = 1051, Aim 2: n = 558), and the Philadelphia Neurodevelopmental Cohort (Aim 1: n = 1087; Aim 2: n = 619). Four different QC approaches were applied to T1-weighted MRI (visual QC, metric QC, automated QC, fMRI-derived QC). We used tetrachoric correlation and inter-rater reliability analyses to examine whether different QC approaches excluded the same participants. We examined differences in age, mental health symptoms, everyday/adaptive functioning, IQ and structural MRI-derived brain indices between participants that were included versus excluded following each QC approach.
Dataset-specific findings revealed mixed results with respect to overlap of QC exclusion. However, in POND and HBN, we found a moderate level of overlap between visual and automated QC approaches (rtet=0.52–0.59). Implementation of QC excluded younger participants, and tended to exclude those with lower IQ, and lower everyday/adaptive functioning scores across several approaches in a dataset-specific manner. Across nearly all datasets and QC approaches examined, excluded participants had lower estimates of cortical thickness and subcortical volume, but this effect did not differ by QC approach.
The results of this study provide insight into the influence of QC decisions on structural pediatric imaging analyses. While different QC approaches exclude different subsets of participants, the variation of influence of different QC approaches on clinical and brain metrics is minimal in large datasets. Overall, implementation of QC tends to exclude participants who are younger, and those who have more cognitive and functional impairment. Given that automated QC is standardized and can reduce between-study differences, the results of this study support the potential to use automated QC for large pediatric neuroimaging datasets.
Journal Article
Physical health of autistic girls and women: a scoping review
by
Babinski, Stephanie
,
Kassee, Caroline
,
Szatmari, Peter
in
Autism
,
Autistic children
,
Autistic Disorder - complications
2020
Background
There is a growing recognition of sex and gender influences in autism. Increasingly, studies include comparisons between sexes or genders, but few have focused on clarifying the characteristics of autistic girls’/women’s physical health.
Methods
A scoping review was conducted to determine what is currently known about the physical health of autistic girls/women. We screened 1112 unique articles, with 40 studies meeting the inclusion criteria. We used a convergent iterative process to synthesize this content into broad thematic areas.
Results
Autistic girls/women experience more overall physical health challenges compared to non-autistic girls/women and to autistic boys/men. Emerging evidence suggests increased prevalence of epilepsy in autistic girls/women compared to non-autistic girls/women and to autistic boys/men. The literature also suggests increased endocrine and reproductive health conditions in autistic girls/women compared to non-autistic girls/women. Findings regarding gastrointestinal, metabolic, nutritional, and immune-related conditions are preliminary and inconsistent.
Limitations
The literature has substantial heterogeneity in how physical health conditions were assessed and reported. Further, our explicit focus on physical health may have constrained the ability to examine interactions between mental and physical health. The widely differing research aims and methodologies make it difficult to reach definitive conclusions. Nevertheless, in keeping with the goals of a scoping review, we were able to identify key themes to guide future research.
Conclusions
The emerging literature suggests that autistic girls/women have heightened rates of physical health challenges compared to non-autistic girls/women and to autistic boys/men. Clinicians should seek to provide holistic care that includes a focus on physical health and develop a women’s health lens when providing clinical care to autistic girls/women.
Journal Article
A systematic review and meta-analysis of neuroimaging studies examining synaptic density in individuals with psychotic spectrum disorders
by
Mirfallah, Giselle
,
Voineskos, Aristotle
,
Husain, Muhammad Ishrat
in
Amygdala
,
Analysis
,
Biomarkers
2024
Background
Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We conducted a systematic review of the literature to identify neuroimaging studies specifically examining synaptic density across the psychosis spectrum.
Methods
PRISMA guidelines on reporting were followed. We systematically searched MEDLINE, Embase, APA PsycINFO, Web of Science and The Cochrane Library from inception to December 8, 2023, and included all original peer-reviewed articles or completed clinical neuroimaging studies of any modality measuring synaptic density in participants with a diagnosis of psychosis spectrum disorder as well as individuals with psychosis-risk states. The NIH quality assessment tool for observational cohort and cross-sectional studies was used for the risk of bias assessment.
Results
Five studies (k = 5) met inclusion criteria, comprising
n
= 128 adults (psychotic disorder;
n
= 61 and healthy volunteers;
n
= 67 and specifically measuring synaptic density via positron emission tomography (PET) imaging of the synaptic vesicle glycoprotein 2 A (SV2A). Three studies were included in our primary meta-analysis sharing the same outcome measure of SV2A binding, volume of distribution (V
T
). Regional SV2A V
T
was reduced in psychotic disorder participants in comparison to healthy volunteers, including the occipital lobe (Mean Difference (MD)= -2.17; 95% CI: -3.36 to -0.98;
P
< 0.001 ), temporal lobe (MD: -2.03; 95% CI: -3.19 to -0.88;
P
< 0.001 ), parietal lobe (MD:-1.61; 95% CI: -2.85 to -0.37;
P
= 0.01), anterior cingulate cortex (MD= -1.47; 95% CI: -2.45 to -0.49;
P
= 0.003), frontal cortex (MD: -1.16; 95% CI: -2.18 to -0.15;
P
= 0.02), amygdala (MD: -1.36; 95% CI: -2.20 to -0.52,
p
= 0.002), thalamus (MD:-1.46; 95% CI:-2.46 to -0.46,
p
= 0.004) and hippocampus (MD= -0.96; 95% CI: -1.59 to -0.33;
P
= 0.003).
Conclusions
Preliminary studies provide in vivo evidence for reduced synaptic density in psychotic disorders. However, replication of findings in larger samples is required prior to definitive conclusions being drawn.
PROSPERO
CRD42022359018.
Summations
• Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology.
• Although there is growing academic interest in the role of synaptic density in the pathophysiology of major mental disorders, we identified only five studies examining synaptic density in individuals with psychotic disorders.
• Synaptic density was significantly lower in several brain regions including the anterior cingulate cortex, hippocampus, occipital, temporal, parietal and frontal cortices, in individuals with psychotic disorders relative to controls.
Considerations
• Preliminary studies provide in vivo evidence for the presence of reduced synaptic density in early course and chronic schizophrenia, however, further investigation in larger samples is required prior to definitive conclusions being drawn regarding changes in synaptic density in schizophrenia.
• Reduction in synaptic density was more significant in several brain regions of individuals with chronic schizophrenia when compared to healthy controls. Presently is difficult to draw definitive conclusions about whether synaptic density reduction is driving the disease or may be influenced by iatrogenic (e.g., pharmacotherapy, psychotherapy, neurostimulation), lifestyle (e.g., smoking, exercise, diet) or other environmental factors (e.g., stress, medical co-morbidity).
Journal Article
Differential association of antioxidative defense genes with white matter integrity in youth bipolar disorder
2022
Oxidative stress is associated with white matter diffusion metrics in adults with bipolar disorder (BD). We examined the association of single-nucleotide polymorphisms in the oxidative stress system, superoxide dismutase-2 (
SOD2
) rs4880 and glutathione peroxidase-3 (
GPX3
) rs3792797 with fractional anisotropy (FA) and radial diffusivity (RD) in youth with BD. Participants included 104 youth (age 17.5 ± 1.7 years; 58 BD, 46 healthy controls). Saliva samples were obtained for genotyping, and diffusion tensor imaging was acquired. Voxel-wise whole-brain white matter diffusion analyses controlled for age, sex, and race. There were significant diagnosis-by-
SOD2
rs4880 interaction effects for FA and RD in major white matter tracts. Within BD, the group with two copies of the G-allele (GG) showed lower FA and higher RD than A-allele carriers. Whereas within the control group, the GG group showed higher FA and lower RD than A-allele carriers. Additionally, FA was higher and RD was lower within the control GG group compared to the BD GG group. No significant findings were observed for
GPX3
rs3793797. The current study revealed that, within matter tracts known to differ in BD, associations of
SOD2
rs4880 GG genotype with both FA and RD differed between BD vs healthy control youth. The SOD2 enzyme encoded by the G-allele, has higher antioxidant capacity than the enzyme encoded by the A-allele. We speculate that the current findings of lower FA and higher RD of the BD GG group compared to the other groups reflects attenuation of the salutary antioxidant effects of GG genotype on white matter integrity in youth with BD, in part due to predisposition to oxidative stress. Future studies incorporating other genetic markers and oxidative stress biomarkers are warranted.
Journal Article
Utility of a virtual small group cognitive behaviour program for autistic children during the pandemic: evidence from a community-based implementation study
2024
Background
Autistic children often experience socioemotional difficulties relating to emotion regulation and mental health problems. Supports for autistic children involve the use of adapted interventions that target emotion regulation and social skills, alongside mental health symptoms. The Secret Agent Society Small Group (SAS: SG), an adapted cognitive behavioural program, has demonstrated efficacy through lab-delivered randomized control trials. However, research is still needed on its effectiveness when delivered by publicly funded, community-based autism providers under real-world ecologically valid conditions, especially within the context of a pandemic. The COVID-19 pandemic has disrupted access to community-based supports and services for autistic children, and programs have adapted their services to online platforms. However, questions remain about the feasibility and clinical utility of evidence-based interventions and services delivered virtually in community-based settings.
Methods
The 9-week SAS: SG program was delivered virtually by seven community-based autism service providers during 2020–2021. The program included the use of computer-based games, role-playing tasks, and home missions. Caregivers completed surveys at three timepoints: pre-, post-intervention, and after a 3-month follow-up session. Surveys assessed caregivers’ perception of the program’s acceptability and level of satisfaction, as well as their child’s social and emotional regulation skills and related mental health challenges.
Results
A total of 77 caregivers (94% gender identity females;
Mean
= 42.1 years,
SD
= 6.5 years) and their children (79% gender identity males;
Mean
= 9.9 years,
SD
= 1.3 years) completed the SAS: SG program. Caregivers agreed that the program was acceptable (95%) and were highly satisfied (90%). Caregivers reported significant reduction in their child’s emotion reactivity from pre- to post-intervention (-1.78 (95% CI, -3.20 to -0.29),
p
= 0.01,
d =
0.36), that continued to decrease after the 3-month booster session (-1.75 (95% CI, -3.34 to -0.16),
p
= 0.02,
d =
0.33). Similarly, improvements in anxiety symptoms were observed (3.05 (95% CI, 0.72 to 5.36),
p
= 0.006,
d
= 0.39).
Conclusions
As online delivery of interventions for autistic children remains popular past the pandemic, our findings shed light on future considerations for community-based services, including therapists and agency leaders, on how best to tailor and optimally deliver virtually based programming.
Trial registration
This study has been registered with ISRCTN Registry (ISRCTN98068608) on 15/09/2023. The study was retroactively registered.
Journal Article
Comparing the stability and reproducibility of brain-behavior relationships found using canonical correlation analysis and partial least squares within the ABCD sample
2024
Canonical correlation analysis (CCA) and partial least squares correlation (PLS) detect linear associations between two data matrices by computing latent variables (LVs) having maximal correlation (CCA) or covariance (PLS). This study compared the similarity and generalizability of CCA- and PLS-derived brain-behavior relationships. Data were accessed from the baseline Adolescent Brain Cognitive Development (ABCD) dataset (N > 9,000, 9–11 years). The brain matrix consisted of cortical thickness estimates from the Desikan-Killiany atlas. Two phenotypic scales were examined separately as the behavioral matrix; the Child Behavioral Checklist (CBCL) subscale scores and NIH Toolbox performance scores. Resampling methods were used to assess significance and generalizability of LVs. LV1 for the CBCL brain relationships was found to be significant, yet not consistently stable or reproducible, across CCA and PLS models (singular value: CCA = .13, PLS = .39, p < .001). LV1 for the NIH brain relationships showed similar relationships between CCA and PLS and was found to be stable and reproducible (singular value: CCA = .21, PLS = .43, p < .001). The current study suggests that stability and reproducibility of brain-behavior relationships identified by CCA and PLS are influenced by the statistical characteristics of the phenotypic measure used when applied to a large population-based pediatric sample.
Journal Article