Historical structural racism in the built environment contributes to health inequities, yet to date, research has almost exclusively focused on racist policy of redlining. We expand upon this conceptualization of historical structural racism by examining the potential associations of probable blockbusting, urban renewal, and proximity to displacement from freeway construction, along with redlining, to multiple contemporary health measures. Analyses linked historical structural racism, measured continuously at the census-tract level using archival data sources, to present-day residents' physical health measures drawn from publicly accessible records for Allegheny County, Pennsylvania. Outcome measures included average life expectancy and the percentage of residents reporting hypertension, stroke, coronary heart disease, smoking, insufficient sleep, sedentary behavior, and no health insurance coverage. Multiple regression analyses were conducted to examine separate and additive associations between structural racism and physical health measures. Redlining, probable blockbusting, and urban renewal were associated with shorter life expectancy and a higher prevalence of cardiovascular conditions, risky health behaviors, and residents lacking health insurance coverage. Probable blockbusting and urban renewal had the most consistent correlations with all 8 health measures, while freeway displacement was not reliably associated with health. Additive models explained a greater proportion of variance in health than any individual structural racism measure alone. Moreover, probable blockbusting and urban renewal accounted for relatively more variance in health compared to redlining, suggesting that research should consider these other measures in addition to redlining. These preliminary correlational findings underscore the importance of considering multiple aspects of historical structural racism in relation to current health inequities and serve as a starting point for additional research.
OBJECTIVE: To describe and interpret Indigenous women's experiences of postpartum depression (PPD) from the perspectives of community advisory board members. DESIGN: Qualitative, descriptive design with a community-engagement approach. SETTING: Virtual group interviews. PARTICIPANTS: Community advisory board members (N = 8) who were tribal employees, citizens of the tribe, and/or family members of citizens who had detailed knowledge of PPD among Indigenous women and issues surrounding their care. METHODS: In video- and audio-recorded virtual group interviews, we asked participants questions using a semistructured interview guide. We used qualitative content analysis to generate results. RESULTS: Major themes included The "Who, What, and Where" of PPD in Indigenous Women; Meanings Attributed to PPD in Indigenous Women; Realities of PPD Care in the Chickasaw Nation; and Feasibility, Acceptability, Perceived Barriers, and Facilitators of a Future Collaboration. CONCLUSION: The participants identified next steps for addressing PPD in the Chickasaw Nation: raise awareness of PPD among providers, patients, and families; improve messaging about PPD to decrease stigma and normalize mental health care; and develop or adapt a culturally appropriate and relevant tool to screen for PPD in Indigenous women.
BACKGROUND: Vaccination during pregnancy reduces the incidence of infections and their associated adverse outcomes in both mothers and infants. The American College of Obstetricians and Gynecologists has recommended influenza and Tdap vaccination during pregnancy since 2004 and 2013, respectively. Several studies have examined disparities in vaccination rates during pregnancy by race/ethnicity. However, none have included American Indians/Alaska Natives as a specific racial/ethnic group on a national level. Current literature suggests that American Indian/Alaska Native infants experience increased morbidity and mortality from both influenza and pertussis infections compared with most other groups in the United States. OBJECTIVE: This study aimed to evaluate the uptake of influenza and Tdap vaccinations during pregnancy by race/ethnicity, with a specific focus on American Indian/Alaska Native people. STUDY DESIGN: This cross-sectional study used data from the Pregnancy Risk Assessment Monitoring System. Comparisons of vaccine uptake across racial/ethnic groups (American Indian/Alaska Native, Asian, non-Hispanic Black, non-Hispanic White, Hispanic, and "None of the above") were evaluated using weighted logistic regression analyses to estimate prevalence odds ratios with 95% confidence intervals. Models were adjusted for maternal age, parity, maternal education, marital status, payment method at delivery, prenatal care in first trimester, maternal smoking status, Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) participation, and receipt of influenza vaccine reported by a health care provider. RESULTS: For both vaccines, Asian respondents had the highest uptake (influenza, 70.1%; Tdap, 68.2%), whereas Black respondents reported the lowest uptake (influenza, 44.4%; Tdap, 57.9%). For the influenza vaccine, American Indian/Alaska Native respondents demonstrated a higher uptake compared with White respondents, and the magnitude of difference increased markedly after adjusting for respondent characteristics (adjusted odds ratio, 1.74; 95% confidence interval, 1.58-1.90). In the unadjusted analyses, Black individuals reported influenza vaccination at approximately half the rate of their White counterparts during pregnancy. This effect was attenuated but remained lower after adjustment for respondent characteristics (adjusted odds ratio, 0.73; 95% confidence interval, 0.70-0.76). For the Tdap vaccine, American Indian/Alaska Native respondents reported lower uptake than White respondents; however, this difference disappeared when adjusted for respondent characteristics (adjusted odds ratio, 0.99; 95% confidence interval, 0.83-1.19). Asian and Hispanic respondents displayed a similar uptake compared with their White counterparts for both vaccines. CONCLUSION: Our findings indicate that there are racial/ethnic disparities in influenza and Tdap vaccination rates among pregnant individuals in the United States. Demonstration of increased uptake among American Indian/Alaska Native people in the crude analysis may reflect the success of various public health interventions through Tribal and Indian Health Service hospitals. Nonetheless, vaccination status during pregnancy remains seriously below national guideline recommendations. Greater measures must be taken to support preventative care in marginalized populations, with particular emphasis on community-driven solutions rooted in justice.
Measures of early neuro-cognitive development that are suitable for use in low-resource settings are needed to enable studies of the effects of early adversity on the developing brain in a global context. These measures should have high acquisition rates and good face and construct validity. Here, we investigated the feasibility of a naturalistic electroencephalography (EEG) paradigm in a low-resource context during childhood. Additionally, we examined the sensitivity of periodic and aperiodic EEG metrics to social and non-social stimuli. We recorded simultaneous 20-channel EEG and eye-tracking in 72 children aged 4-12 years (45 females) while they watched videos of women singing nursery rhymes and moving toys, selected to represent familiar childhood experiences. These measures were part of a feasibility study that assessed the feasibility and acceptability of a follow-up data collection of the South African Safe Passage Study, which tracks environmental adversity and brain and cognitive development from before birth up until childhood. We examined whether data quantity and quality varied with child characteristics and the sensitivity of varying EEG metrics (canonical band power in the theta and alpha band and periodic and aperiodic features of the power spectra). We found that children who completed the EEG and eye-tracking assessment were, in general, representative of the full cohort. Data quantity was higher in children with greater visual attention to the stimuli. Out of the tested EEG metrics, periodic measures in the theta frequency range were most sensitive to condition differences, compared to alpha range measures and canonical and aperiodic EEG measures. Our results show that measuring EEG during ecologically valid social and non-social stimuli is feasible in low-resource settings, is feasible for most children, and produces robust indices of social brain function. This work provides preliminary support for testing longitudinal links between social brain function, environmental factors, and emerging behaviors.
Brain , Electroencephalography , Child , Humans , Female , Brain Mapping , Cognition
Precision health refers to the use of individualised biomarkers or predictive models to provide more tailored information about an individual's likely prognosis. For child psychiatry and psychology, we argue that this approach requires a focus on neurocognitive measures collected in early life and at large scale. However, the large sample sizes necessary to uncover individual-level predictors are currently rare in studies of neurodevelopmental conditions in early childhood. We recommend two strategies going forward: first, including neurocognitive measures in new national cohort studies, and second, synergising measures and data across currently funded longitudinal studies.
Child Development , Precision Medicine , Humans , Child Development/physiology , Child , Neurodevelopmental Disorders , Child, Preschool
Many species have been intentionally introduced to new regions for their benefits. Some of these alien species cause damage, others do not (or at least have not yet). There are several approaches to address this problem: prohibit taxa that will cause damage, try to limit damages while preserving benefits, or promote taxa that are safe. In the present article, we unpack the safe list approach, which we define as "a list of taxa alien to the region of interest that are considered of sufficiently low risk of invasion and impact that the taxa can be widely used without concerns of negative impacts." We discuss the potential use of safe lists in the management of biological invasions; disentangle aspects related to the purpose, development, implementation, and impact of safe lists; and provide guidance for those considering to develop and implement such lists.
Almaatouq et al. propose an integrative experiment design space combined with large samples for scientific advancement. We argue recent innovative designs combining closed-loop experiment designs and Bayesian optimisation allow for integrative experiments at an individual level during a single session, circumventing the necessity for large samples. This method can be applied across disciplines, including developmental and clinical research.
Behavioral Sciences , Research Design , Humans , Bayes Theorem
BACKGROUND: Existing evidence indicates that atypical sensory reactivity is a core characteristic of autism, and has been linked to both anxiety (and its putative infant precursor of fearfulness) and repetitive behaviours. However, most work has used cross-sectional designs and not considered the differential roles of hyperreactivity and hyporeactivity to sensory inputs, and is thus limited in specificity. METHODS: 161 infants with and without an elevated likelihood of developing autism and attention-deficit hyperactivity disorder (ADHD) were followed from 10 to 36 months of age. Parents rated an infant precursor of later anxiety (fearfulness) using the Infant Behaviour Questionnaire at 10 and 14 months, and the Early Childhood Behavioural Questionnaire at 24 months, and sensory hyperreactivity and hyporeactivity at 10, 14 and 24 months using the Infant Toddler Sensory Profile. Domains of autistic traits (restrictive and repetitive behaviours; RRB, and social communication interaction, SCI) were assessed using the parent-rated Social Responsiveness Scale at 36 months. Cross-lagged models tested (a) paths between fearfulness and hyperreactivity at 10-24 months, and from fearfulness and hyperreactivity to later autism traits, (b) the specificity of hyperreactivity effects by including hyporeactivity as a correlated predictor. RESULTS: Hyperreactivity at 14 months was positively associated with fearfulness at 24 months, and hyperreactivity at 24 months was positively associated with SCI and RRB at 36 months. When hyporeactivity was included in the model, paths between hyperreactivity and fearfulness remained, but paths between hyperreactivity and autistic traits became nonsignificant. CONCLUSIONS: Our findings indicate that alterations in early sensory reactivity may increase the likelihood of showing fearfulness in infancy, and relate to later social interactions and repetitive behaviours, particularly in individuals with a family history of autism or ADHD.
BACKGROUND AND OBJECTIVES: There are well-documented links between structural racism and inequities in children's opportunities. Yet, when it comes to understanding the role of the built environment, a disproportionate focus on redlining obscures other historical policies and practices such as blockbusting, freeway displacement, and urban renewal that may impact contemporary child development. We hypothesized that historical structural racism in Allegheny County, Pennsylvania's, built environment would be associated with fewer contemporary educational, socioeconomic, and health opportunities. We also hypothesized that these measures would explain more collective variance in children's opportunities than redlining alone. METHODS: We used geospatial data from the US Census, Mapping Inequality Project, and other archival sources to construct historical measures of redlining, blockbusting, freeway displacement, and urban renewal in ArcGIS at the census tract level. These were linked with data from the Child Opportunity Index 2.0 to measure children's opportunities across domains of education, socioeconomic status, and health. We ran spatial regression analyses in Stata 18.0 to examine individual and collective associations between structural racism and children's opportunities. RESULTS: Historical redlining, blockbusting, and urban renewal were largely associated with fewer contemporary educational, socioeconomic, and health opportunities, and explained up to 47.4% of the variance in children's opportunities. The measures collectively explained more variance in children's opportunities than redlining alone. CONCLUSIONS: In support of our hypotheses, novel measures of structural racism were related to present-day differences in children's opportunities. Findings lay the groundwork for future research focused on repairing longstanding harm perpetuated by structural racism.
Racism , Systemic Racism , Child , Humans , Child Development , Social Class , Pennsylvania , Built Environment , Residence Characteristics
BACKGROUND: Fine motor skills are heritable and comprise important milestones in development, and some evidence suggests that impairments in fine motor skills are associated with neurodevelopmental conditions, psychiatric disorders, and poor educational outcomes. METHODS: In a preregistered study of 9625 preschool children from TEDS (Twins Early Development Study), fine motor assessments (drawing, block building, folding, and questionnaires) were conducted at 2, 3, and 4 years of age. A cross-age fine motor score was derived using principal component analysis. Multivariate regression analysis was used to examine the relationships between the fine motor score and neurodevelopmental traits, psychopathology, and educational outcomes at 3 later ages (7-8, 12, and 16 years) and cross-age psychopathology composite scores. Polygenic scores (PGSs) were created for attention-deficit/hyperactivity disorder (ADHD), autism, schizophrenia, anxiety, major depressive disorder, obsessive-compulsive disorder, and years of education. We ran single-PGS models and a multi-PGS model. RESULTS: Fine motor skills were negatively associated with neurodevelopmental traits and psychopathology across childhood and adolescence and positively associated with educational achievement in adolescence (ß = 0.25, p < .001). Superior fine motor skills were associated with a higher years-of-education PGS (ß = 0.07, p < .001), a lower ADHD PGS (ß = -0.04, p = .011), and a higher anxiety PGS (ß = 0.03, p = .040). Similarly, the multi-PGS model retained the PGSs for years of education (ß = 0.07), ADHD (ß = -0.03), and anxiety (ß = 0.01). A non-preregistered analysis in an independent preschool sample replicated the ADHD PGS association, but not the years of education or anxiety PGS associations. CONCLUSIONS: Fine motor skills are linked genetically and phenotypically to later neurodevelopment, psychopathology, and educational outcomes. Future work should investigate the mechanisms that underlie the role of fine motor development in later outcomes.
Academic Success , Attention Deficit Disorder with Hyperactivity , Depressive Disorder, Major , Adolescent , Humans , Child, Preschool , Child , Motor Skills , Attention Deficit Disorder with Hyperactivity/genetics , Attention Deficit Disorder with Hyperactivity/psychology , Educational Status
AIM: To characterize early changes in developmental ability, language, and adaptive behaviour in infants diagnosed with tuberous sclerosis complex (TSC), and determine whether clinical features of epilepsy influence this pathway. METHOD: Prospective, longitudinal data were collected within the Early Development in Tuberous Sclerosis (EDiTS) Study to track development of infants with TSC (n = 32) and typically developing infants (n = 33) between 3 and 24 months of age. Questionnaire and observational measures were used at up to seven timepoints to assess infants' adaptive behaviour, developmental ability, language, and epilepsy. RESULTS: A significant group by age interaction effect showed that infants with TSC had lower adaptive functioning at 18 to 24 months old (intercept = 88.12, slope estimate = -0.82, p < 0.001) and lower developmental ability scores from 10 months old (intercept = 83.33, slope estimate = -1.44, p < 0.001) compared to typically developing infants. Early epilepsy severity was a significant predictor of these emerging developmental (R2 = 0.35, p = 0.004, 95% confidence interval [CI] -0.08 to -0.01) and adaptive behaviour delays (R2 = 0.34, p = 0.004, 95% CI -0.05 to -0.01]). Lower vocabulary production (intercept = -1.25, slope = -0.12, p < 0.001) and comprehension scores (intercept = 2.39, slope estimate = -0.05, p < 0.001) in infants with TSC at 24 months old were not associated with epilepsy severity. INTERPRETATION: Divergence of developmental ability and adaptive functioning skills occur in infants with TSC from 10 and 18 months, respectively. Associations between early epilepsy severity and impaired development supports the importance of early intervention to reduce seizure severity.
Epilepsy , Tuberous Sclerosis , Infant , Humans , Child, Preschool , Prospective Studies , Tuberous Sclerosis/complications , Tuberous Sclerosis/diagnosis , Longitudinal Studies , Epilepsy/complications , Seizures/complications
BACKGROUND: Autism is a heterogeneous neurodevelopmental condition accompanied by differences in brain connectivity. Structural connectivity in autism has mainly been investigated within the white matter. However, many genetic variants associated with autism highlight genes related to synaptogenesis and axonal guidance, thus also implicating differences in intrinsic (i.e., gray matter) connections in autism. Intrinsic connections may be assessed in vivo via so-called intrinsic global and local wiring costs. METHODS: Here, we examined intrinsic global and local wiring costs in the brain of 359 individuals with autism and 279 healthy control participants ages 6 to 30 years from the EU-AIMS LEAP (Longitudinal European Autism Project). FreeSurfer was used to derive surface mesh representations to compute the estimated length of connections required to wire the brain within the gray matter. Vertexwise between-group differences were assessed using a general linear model. A gene expression decoding analysis based on the Allen Human Brain Atlas was performed to link neuroanatomical differences to putative underpinnings. RESULTS: Group differences in global and local wiring costs were predominantly observed in medial and lateral prefrontal brain regions, in inferior temporal regions, and at the left temporoparietal junction. The resulting neuroanatomical patterns were enriched for genes that had been previously implicated in the etiology of autism at genetic and transcriptomic levels. CONCLUSIONS: Based on intrinsic gray matter connectivity, the current study investigated the complex neuroanatomy of autism and linked between-group differences to putative genomic and/or molecular mechanisms to parse the heterogeneity of autism and provide targets for future subgrouping approaches.
Autism Spectrum Disorder , White Matter , Humans , Gray Matter/diagnostic imaging , Autism Spectrum Disorder/diagnostic imaging , Autism Spectrum Disorder/genetics , Magnetic Resonance Imaging/methods , Cerebral Cortex , Brain/diagnostic imaging , White Matter/diagnostic imaging , Genomics
Background: Most research on early outcomes in infants with a family history (FH) of autism has focussed on categorically defined autism, although some have language and developmental delays. Less is known about outcomes in infants with a FH of attention deficit hyperactivity disorder (ADHD). Methods: Infants with and without a FH of autism and/or ADHD, due to a first-degree relative with either or both conditions, were recruited at 5 or 10 months. Three year outcomes were characterised using latent profile analysis (LPA) across measures of cognitive ability, adaptive functioning and autism, ADHD and anxiety traits (n = 131). We additionally ran an LPA using only autism and ADHD measures, and the broader LPA in an independent cohort (n = 139) and in both cohorts combined (n = 270). Results: A Low Developmental Level + High Behavioural Concerns class had elevated autism, ADHD and anxiety scores, low cognitive and adaptive function, and included all but one child with autism. A Low Developmental Level + Typical Behaviour class had average cognitive ability and typical behaviour but low adaptive function. A Typical Developmental Level + Some Behavioural Concerns class had average cognitive and adaptive function but slightly elevated behaviour scores. A High Developmental Level + Typical Behaviour class had above average cognitive ability and typical behaviour. All four LPAs identified classes characterised by combinations of either, or both, Low Development Level and elevated behaviour scores, as well as a typically developing class. No classes had elevated autism or ADHD traits in isolation. Conclusions: Some infants with a FH of autism or ADHD have atypical developmental and behavioural outcomes, but do not show strong autism or ADHD traits in isolation. The field needs to recalibrate aims and methods to embrace the broader transdiagnostic pattern of outcomes seen in these infants.
BACKGROUND: Growing evidence suggests maternal stress contributes to the development of adverse pregnancy outcomes that are associated with cardiovascular and cardiometabolic risk in birthing persons. Mindfulness-based interventions may positively affect psychological stress in pregnancy and, in turn, reduce stress. However, few study authors have examined the effects of mindfulness-based interventions on adverse pregnancy outcomes that heighten cardiovascular risk. OBJECTIVE: The aim of this study was to appraise available literature examining the effects of mindfulness-based interventions delivered during pregnancy on adverse pregnancy outcomes associated with future cardiovascular and cardiometabolic disease risk. METHODS: In this systematic review, multiple electronic databases were searched using major keywords, including "mindfulness-based intervention," "pregnancy," "preterm delivery," "gestational diabetes," "small for gestational age," "preeclampsia," and "hypertension in pregnancy" during February 2023. RESULTS: Six studies using mindfulness-based interventions during pregnancy were included. The review indicated that these interventions were largely effective at reducing prenatal stress; however, the overall effects of interventions were mixed concerning their impact on pregnancy complications. Study authors examining the effects on gestational diabetes-related outcomes reported significant improvements in blood glucose levels, hemoglobin A1c, and oral glucose tolerance. Outcomes were mixed or inconclusive related to the effects of interventions on the incidence of preterm birth, birth of a small-for-gestational-age newborn, and preeclampsia. CONCLUSIONS: Mitigating cardiovascular and cardiometabolic risk-associated adverse pregnancy outcomes through mindfulness-based approaches may represent an emerging field of study. The few studies and limited, mixed findings synthesized in this review indicate that high-validity studies are warranted to examine the effects of mindfulness-based interventions on pregnancy complications that contribute to cardiovascular-related maternal morbidity and suboptimal life course health for diverse birthing persons.
BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental conditions accompanied by differences in brain development. Neuroanatomical differences in autism are variable across individuals and likely underpin distinct clinical phenotypes. To parse heterogeneity, it is essential to establish how the neurobiology of ASD is modulated by differences associated with co-occurring conditions, such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to (1) investigate between-group differences in autistic individuals with and without co-occurring ADHD, and to (2) link these variances to putative genomic underpinnings. METHODS: We examined differences in cortical thickness (CT) and surface area (SA) and their genomic associations in a sample of 533 individuals from the Longitudinal European Autism Project. Using a general linear model including main effects of autism and ADHD, and an ASD-by-ADHD interaction, we examined to which degree ADHD modulates the autism-related neuroanatomy. Further, leveraging the spatial gene expression data of the Allen Human Brain Atlas, we identified genes whose spatial expression patterns resemble our neuroimaging findings. RESULTS: In addition to significant main effects for ASD and ADHD in fronto-temporal, limbic, and occipital regions, we observed a significant ASD-by-ADHD interaction in the left precentral gyrus and the right frontal gyrus for measures of CT and SA, respectively. Moreover, individuals with ASD + ADHD differed in CT to those without. Both main effects and the interaction were enriched for ASD-but not for ADHD-related genes. LIMITATIONS: Although we employed a multicenter design to overcome single-site recruitment limitations, our sample size of N = 25 individuals in the ADHD only group is relatively small compared to the other subgroups, which limits the generalizability of the results. Also, we assigned subjects into ADHD positive groupings according to the DSM-5 rating scale. While this is sufficient for obtaining a research diagnosis of ADHD, our approach did not take into account for how long the symptoms have been present, which is typically considered when assessing ADHD in the clinical setting. CONCLUSION: Thus, our findings suggest that the neuroanatomy of ASD is significantly modulated by ADHD, and that autistic individuals with co-occurring ADHD may have specific neuroanatomical underpinnings potentially mediated by atypical gene expression.
Attention Deficit Disorder with Hyperactivity , Autism Spectrum Disorder , Autistic Disorder , Humans , Autistic Disorder/diagnostic imaging , Autistic Disorder/genetics , Autistic Disorder/complications , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Attention Deficit Disorder with Hyperactivity/genetics , Attention Deficit Disorder with Hyperactivity/complications , Neuroanatomy , Brain/diagnostic imaging , Autism Spectrum Disorder/diagnostic imaging , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/complications , Genomics
The specialised regional functionality of the mature human cortex partly emerges through experience-dependent specialisation during early development. Our existing understanding of functional specialisation in the infant brain is based on evidence from unitary imaging modalities and has thus focused on isolated estimates of spatial or temporal selectivity of neural or haemodynamic activation, giving an incomplete picture. We speculate that functional specialisation will be underpinned by better coordinated haemodynamic and metabolic changes in a broadly orchestrated physiological response. To enable researchers to track this process through development, we develop new tools that allow the simultaneous measurement of coordinated neural activity (EEG), metabolic rate, and oxygenated blood supply (broadband near-infrared spectroscopy) in the awake infant. In 4- to 7-month-old infants, we use these new tools to show that social processing is accompanied by spatially and temporally specific increases in coupled activation in the temporal-parietal junction, a core hub region of the adult social brain. During non-social processing, coupled activation decreased in the same region, indicating specificity to social processing. Coupling was strongest with high-frequency brain activity (beta and gamma), consistent with the greater energetic requirements and more localised action of high-frequency brain activity. The development of simultaneous multimodal neural measures will enable future researchers to open new vistas in understanding functional specialisation of the brain.
Brain , Neuroimaging , Adult , Humans , Infant , Brain/diagnostic imaging , Neuroimaging/methods , Electroencephalography/methods
Autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) are highly prevalent neurodevelopmental conditions that often co-occur and present both common and distinct neurodevelopmental profiles. Studying the developmental pathways leading to the emergence of ASD and/or ADHD symptomatology is crucial in understanding neurodiversity and discovering the mechanisms that underpin it. This study used functional near-infrared spectroscopy (fNIRS) to investigate differences in cortical specialization to social stimuli between 4- to 6-month-old infants at typical and elevated likelihood of ASD and/or ADHD. Results showed that infants at both elevated likelihood of ASD and ADHD had reduced selectivity to vocal sounds in left middle and superior temporal gyrus. Furthermore, infants at elevated likelihood of ASD showed attenuated responses to visual social stimuli in several cortical regions compared to infants at typical likelihood. Individual brain responses to visual social stimuli were associated with later autism traits, but not ADHD traits. These outcomes support our previous observations showing atypical social brain responses in infants at elevated likelihood of ASD and align with later atypical brain responses to social stimuli observed in children and adults with ASD. These findings highlight the importance of characterizing antecedent biomarkers of atypicalities in processing socially relevant information that might contribute to both phenotypic overlap and divergence across ASD and ADHD conditions and their association with the later emergence of behavioural symptoms.
Attention Deficit Disorder with Hyperactivity , Autism Spectrum Disorder , Child , Infant , Adult , Humans , Prospective Studies , Brain , Temporal Lobe
Despite the large number of microfluidic devices that have been described over the past decade for the study of tissues and organs, few have become widely adopted. There are many reasons for this lack of adoption, primarily that devices are constructed for a single purpose or because they are highly complex and require relatively expensive investment in facilities and training. Here, we describe a microphysiological system (MPS) that is simple to use and provides fluid channels above and below cells, or tissue biopsies, maintained on a disposable, poly(methyl methacrylate), carrier held between polycarbonate outer plates. All other fittings are standard Luer sizes for ease of adoption. The carrier can be coated with cells on both sides to generate membrane barriers, and the devices can be established in series to allow medium to flow from one cell layer to another. Furthermore, the carrier containing cells can be easily removed after treatment on the device and the cells can be visualized or recovered for additional off-chip analysis. A 0.4 µm membrane with cell monolayers proved most effective in maintaining separate fluid flows, allowing apical and basal surfaces to be perfused independently. A panel of different cell lines (Caco-2, HT29-MTX-E12, SH-SY5Y, and HUVEC) were successfully maintained in the MPS for up to 7 days, either alone or on devices connected in series. The presence of tight junctions and mucin was expressed as expected by Caco-2 and HT-29-MTX-E12, with Concanavalin A showing uniform staining. Addition of Annexin V and PI showed viability of these cells to be >80% at 7 days. Bacterial extracellular vesicles (BEVs) produced by Bacteroides thetaiotaomicron and labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbo-cyanine perchlorate (DiD) were used as a model component of the human colonic microbiota and were visualized translocating from an apical surface containing Caco-2 cells to differentiated SH-SY5Y neuronal cells cultured on the basal surface of connected devices. The newly described MPS can be easily adapted, by changing the carrier to maintain spheroids, pieces, or slices of biopsy tissue and joined in series to study a variety of cell and tissue processes. The cell layers can be made more complex through the addition of multiple cell types and/or different patterning of extracellular matrix and the ability to culture cells adjacent to one another to allow study of cell:cell transfer, e.g., passive or active drug transfer, virus or bacterial entry or BEV uptake and transfer.
A paradigm shift in research culture is required to ease perceived tensions between autistic people and the biomedical research community. As a group of autistic and non-autistic scientists and stakeholders, we contend that through participatory research, we can reject a deficit-based conceptualization of autism while building a shared vision for a neurodiversity-affirmative biomedical research paradigm.
Autistic Disorder , Biomedical Research , Humans , Biomedical Research/ethics , Behavior , Community-Based Participatory Research
