Search

This study explored the interactions among prenatal stress, child sex, and polygenic risk scores (PGS) for attention‐deficit/hyperactivity disorder (ADHD) on structural developmental changes of brain regions implicated in ADHD. We used data from two population‐based birth cohorts: Growing Up in Singapore Towards healthy Outcomes (GUSTO) from Singapore (n = 113) and Generation R from Rotterdam, the Netherlands (n = 433). Prenatal stress was assessed using questionnaires. We obtained latent constructs of prenatal adversity and prenatal mood problems using confirmatory factor analyses. The participants were genotyped using genome‐wide single nucleotide polymorphism arrays, and ADHD PGSs were computed. Magnetic resonance imaging scans were acquired at 4.5 and 6 years (GUSTO), and at 10 and 14 years (Generation R). We estimated the age‐related rate of change for brain outcomes related to ADHD and performed (1) prenatal stress by sex interaction models, (2) prenatal stress by ADHD PGS interaction models, and (3) 3‐way interaction models, including prenatal stress, sex, and ADHD PGS. We observed an interaction between prenatal stress and ADHD PGS on mean cortical thickness annual rate of change in Generation R (i.e., in individuals with higher ADHD PGS, higher prenatal stress was associated with a lower rate of cortical thinning, whereas in individuals with lower ADHD PGS, higher prenatal stress was associated with a higher rate of cortical thinning). None of the other tested interactions were statistically significant. Higher prenatal stress may promote a slower brain developmental rate during adolescence in individuals with higher ADHD genetic vulnerability, whereas it may promote a faster brain developmental rate in individuals with lower ADHD genetic vulnerability. [ABSTRACT FROM AUTHOR]

Background We aimed to investigate the associations of pre-existing maternal cardiovascular disease (CVD) with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID) in offspring. Methods This population-based cohort study included singletons live-born without major malformations in Sweden (n  = 2 699 675) and British Columbia (BC), Canada (n  = 887 582) during 1990–2019, with follow-up from age 1 year until the outcome, death, emigration or December 2020, whichever came first. The primary exposure was defined as a composite CVD diagnosed prior to conception: cerebrovascular disease, arrhythmia, heart failure, valvular and congenital heart diseases. The incidences of ADHD, ASD and ID, comparing offspring of mothers with versus without CVD, were calculated as adjusted hazard ratios (aHRs). These results were compared with models using paternal CVD as negative control exposure. Results Compared with offspring of mothers without CVD, offspring of mothers with CVD had 1.15-fold higher aHRs of ADHD [95% confidence interval (CI): 1.10–1.20] and ASD (95% CI 1.07–1.22). No association was found between maternal CVD and ID. Stratification by maternal CVD subtypes showed increased hazards of ADHD for maternal heart failure (HR 1.31, 95% CI 1.02–1.61), cerebrovascular disease (HR 1.20, 95% CI 1.08–1.32), congenital heart disease (HR 1.18, 95% CI 1.08–1.27), arrhythmia (HR 1.13, 95% CI 1.08–1.19) and valvular heart disease (HR 1.12, 95% CI 1.00–1.24). Increased hazards of ASD were observed for maternal cerebrovascular disease (HR 1.25, 95% CI 1.04–1.46), congenital heart disease (HR 1.17, 95% CI 1.01–1.33) and arrythmia (HR 1.12, 95% CI 1.01–1.21). Paternal CVD did not show associations with ADHD, ASD or ID, except for cerebrovascular disease which showed associations with ADHD and ASD. Conclusions In this large cohort study, pre-existing maternal CVD was associated with increased risk of ADHD and ASD in offspring. [ABSTRACT FROM AUTHOR]

Prenatal exposure to maternal depression and serotonin reuptake inhibitor (SRI) antidepressants both affect the development of the hypothalamic–pituitary–adrenal (HPA) system, possibly via the neurotransmitter serotonin (5HT). In a community cohort, we investigated the impact of two factors that shape prenatal 5HT signaling (prenatal SRI [pSRI] exposure and child SLC6A4 genotype) on HPA activity at age 6 years. Generalized estimating equation (GEE) models were used to study associations between cortisol reactivity, pSRI exposure, and child SLC6A4 genotype, controlling for maternal depression, child age, and sex (48 pSRI exposed, 74 nonexposed). Salivary cortisol levels were obtained at five time points during a laboratory stress challenge: arrival at the laboratory, following two sequential developmental assessments, and then 20 and 40 min following the onset of a stress‐inducing cognitive/social task. Cortisol decreased from arrival across both developmental assessments, and then increased across both time points following the stress challenge in both groups. pSRI‐exposed children had lower cortisol levels across all time points. In a separate GEE model, we observed a lower cortisol stress response among children with LG/S alleles compared with children with La/La alleles, and this was particularly evident among children of mothers reporting greater third trimester depressed mood. Our findings suggest that pSRI exposure and a genetic factor associated with modulating 5HT signaling shaped HPA reactivity to a laboratory stress challenge at school age. [ABSTRACT FROM AUTHOR]

Placebo responses are frequently observed in research studies and clinical contexts, yet there is limited knowledge about the placebo effect among children with neurodevelopmental disorders. Here, we review the placebo effect in autism spectrum disorder (ASD). Placebo responses are widely evident in ASD clinical trials and could partly operate via so‐called placebo‐by‐proxy, whereby caregivers or clinicians indirectly shape patient outcomes. Understanding the role of placebo effects in ASD may help discern genuine treatment effects from contextual factors in clinical trials. The much less studied nocebo effect, or negative placebo, might contribute to the experience of side effects in ASD treatments but empirical data is missing. Better knowledge about placebo and nocebo mechanisms may contribute to the development of more effective research designs, such as three‐armed designs that account for natural history, and improved treatments for ASD symptoms. At a clinical level, deeper knowledge about placebo and nocebo effects may optimize the delivery of care for individuals with ASD in the future. What this paper adds: Placebo responses are evident in autism spectrum disorder (ASD) clinical trials.Placebo responses in ASD are likely dependent on a placebo‐by‐proxy mechanism. What this paper adds: Placebo responses are evident in autism spectrum disorder (ASD) clinical trials.Placebo responses in ASD are likely dependent on a placebo‐by‐proxy mechanism. [ABSTRACT FROM AUTHOR]

The authors hypothesized that a social and emotional learning (SEL) program involving mindfulness and caring for others, designed for elementary school students, would enhance cognitive control, reduce stress, promote well-being and prosociality, and produce positive school outcomes. To test this hypothesis, 4 classes of combined 4th and 5th graders (N = 99) were randomly assigned to receive the SEL with mindfulness program versus a regular social responsibility program. Measures assessed executive functions (EFs), stress physiology via salivary cortisol, well-being (self-reports), prosociality and peer acceptance (peer reports), and math grades. Relative to children in the social responsibility program, children who received the SEL program with mindfulness (a) improved more in their cognitive control and stress physiology; (b) reported greater empathy, perspective-taking, emotional control, optimism, school self-concept, and mindfulness, (c) showed greater decreases in self-reported symptoms of depression and peer-rated aggression, (d) were rated by peers as more prosocial, and (e) increased in peer acceptance (or sociometric popularity). The results of this investigation suggest the promise of this SEL intervention and address a lacuna in the scientific literature--identifying strategies not only to ameliorate children's problems but also to cultivate their well-being and thriving. Directions for future research are discussed.

Data tracking is a common feature of pain e-health applications, however, viewing visualizations of this data has not been investigated for its potential as an intervention itself. We conducted a pilot feasibility parallel randomized cross-over trial, 1:1 allocation ratio. Participants were youth age 12–18 years recruited from a tertiary-level pediatric chronic pain clinic in Western Canada. Participants completed two weeks of Ecological Momentary Assessment (EMA) data collection, one of which also included access to a data visualization platform to view their results. Order of weeks was randomized, participants were not masked to group assignment. Objectives were to establish feasibility related to recruitment, retention, and participant experience. Of 146 youth approached, 48 were eligible and consented to participation, two actively withdrew prior to the EMA. Most participants reported satisfaction with the process and provided feedback on additional variables of interest. Technical issues with the data collection platform impacted participant experience and data analysis, and only 48% viewed the visualizations. Four youth reported adverse events not related to visualizations. Data visualization offers a promising clinical tool, and patient experience feedback is critical to modifying the platform and addressing technical issues to prepare for deployment in a larger trial. [ABSTRACT FROM AUTHOR]

Background: Prenatal antibiotic exposure induces changes in the maternal microbiome, which could influence the development of the infant's microbiome–gut–brain axis. Objectives: We assessed whether prenatal antibiotic exposure is associated with an increased risk of autism spectrum disorder (ASD) in offspring born at term. Methods: This population‐based retrospective cohort study included everyone who delivered a live singleton‐term infant in British Columbia, Canada between April 2000 and December 2014. Exposure was defined as filling antibiotic prescriptions during pregnancy. The outcome was an ASD diagnosis from the British Columbia Autism Assessment Network, with a follow‐up to December 2016. To examine the association among pregnant individuals treated for the same indication, we studied a sub‐cohort diagnosed with urinary tract infections. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios (HR). The analysis was stratified by sex, trimester, cumulative duration of exposure, class of antibiotic, and mode of delivery. We ran a conditional logistic regression of discordant sibling pairs to control for unmeasured environmental and genetic confounding. Results: Of the 569,953 children included in the cohort, 8729 were diagnosed with ASD (1.5%) and 169,922 were exposed to prenatal antibiotics (29.8%). Prenatal antibiotic exposure was associated with an increased risk of ASD (HR 1.10, 95% confidence interval [CI] 1.05, 1.15), particularly for exposure during the first and second trimesters (HR 1.11, 95% CI 1.04, 1.18 and HR 1.09, 95% CI 1.03, 1.16, respectively), and exposure lasting ≥15 days (HR 1.13, 95% CI 1.04, 1.23). No sex differences were observed. The association was attenuated in the sibling analysis (adjusted odds ratio 1.04, 95% CI 0.92, 1.17). Conclusions: Prenatal antibiotic exposure was associated with a small increase in the risk of ASD in offspring. Given the possibility of residual confounding, these results should not influence clinical decisions regarding antibiotic use during pregnancy. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs) are the most popular antidepressant medications used to manage perinatal mood disturbances, yet our understanding of how they affect the microbiome‐gut‐brain axis of the mother and offspring is limited. The purpose of this study was to determine how peripartum SSRI treatment may prevent the effects of gestational stress on plasticity in the maternal hippocampus, plasticity in the neonatal brain and related changes in gut microbiota. To do this Sprague–Dawley female rats were left untreated or subjected to unpredictable stress during pregnancy. Half of the females were supplemented daily with fluoxetine. On postpartum day 2 brains were collected for measurement of plasticity (neurogenesis and microglia content) in the maternal hippocampus and in the neonatal brain. Glucocorticoid receptor density was also investigated in the maternal hippocampus. Microbiota composition was analyzed in fecal samples of dams during and after pregnancy, and colon tissue samples from offspring on postnatal day 2. Main findings show there are significant changes to the maternal microbiome‐gut‐brain axis that may be fundamental to mediating plasticity in the maternal hippocampus. In addition, there is significant impact of gestational stress on neonatal gut microbiota and brain microglia density, while the effects of SSRIs are limited. This is the first study to explore the impact of gestational stress and SSRIs on the microbiome‐gut‐brain axis in the mother and neonate. Findings from this study will help inform pathways to intervention strategies including stress reduction techniques and/or microbiota targeted nutritional approaches directed towards improving maternal gut health and outcomes for mother and neonate. [ABSTRACT FROM AUTHOR]

Neurodevelopmental disability in children covers a vast array of congenital and acquired long-term conditions associated with brain or neuromuscular impairments that impact function. While some presentations of neurodevelopmental disability align with diagnostic labels, many do not, leaving children whose conditions don't fit neatly under diagnostic labels struggling to access services or families and professionals feeling pressured to assign a diagnostic label in order to access services. In this paper, we (1) discuss the evidence showing that there is often a mismatch between a child's neurodevelopmental diagnosis, or lack of diagnosis, and function, (2) comment on the inequities exacerbated by diagnosis-based approaches for services, and (3) highlight the potential benefits of using a function and participation-based approach for providing services to children with neurodevelopmental disabilities. We close with three calls to action for function and participation-based approaches that could better support equitable services for children with neurodevelopmental disabilities. [ABSTRACT FROM AUTHOR]

Learning difficulties in preterm infants are thought to reflect impairment in arousal regulation. We examined relationships among gestational age, learning speed, and behavioral and physiological reactivity in 55 preterm and 49 full-term infants during baseline, contingency, and nonreinforcement phases of a conjugate mobile paradigm at 3 months corrected age. For all infants, negative affect, looking duration, and heart rate levels increased during contingency and nonreinforcement phases, whereas respiratory sinus arrhythmia (RSA, an index of parasympathetic activity) decreased and cortisol did not change. Learners showed greater RSA suppression and less negative affect than nonlearners. This pattern was particularly evident in the preterm group. Overall, preterm infants showed less learning, spent less time looking at the mobile, and had lower cortisol levels than full-term infants. Preterm infants also showed greater heart rate responses to contingency and dampened heart rate responses to nonreinforcement compared to full-term infants. Findings underscore differences in basal and reactivity measures in preterm compared to full-term infants and suggest that the capacity to regulate parasympathetic activity during a challenge enhances learning in preterm infants. (Contains 3 tables and 4 figures.)

Emotions are at the core of all human experiences, but talking about emotions is challenging, particularly in the context of medical encounters focused on somatic symptoms. Transparent, normalizing, and validating communication about the mind-body connection opens the door for respectful, open dialogue between the family and members of the care team, acknowledging the lived experience that is brought to the table in understanding the problem and co-creating a solution. [ABSTRACT FROM AUTHOR]