Peer victimization and the association with hippocampal development and working memory in children with ADHD and typically-developing children

The symptoms of hyperactivity-impulsivity and inattention displayed by children with ADHD put them at risk of experiencing peer victimization. Hippocampal maturation, may reduce a child’s vulnerability to the experience of peer victimization, as it has been associated with decreased ADHD symptomatology. Working memory is an important executive function in the formation and maintenance of social relationships, which is often impaired in ADHD. We aimed to evaluate the relationship between problem behaviours, peer victimization, hippocampal morphology, and working memory in children with and without ADHD. 218 typically-developing participants (50.5% male) and 232 participants diagnosed with ADHD (77.6% male) were recruited. The ADHD group was subdivided into inattentive (ADHD-I) or combined (ADHD-C) types. The Child Behavior Checklist measured problem behaviours and peer victimization. Children underwent Magnetic Resonance Imaging (MRI). Hippocampal subfield volumes were obtained using FreeSurfer. The Wechsler Intelligence Scale for Children-fifth edition measured working memory (WM). The ADHD-C group displayed significantly higher levels of problem behaviours and peer victimization (all, p \u3c 0.001), compared to the other groups. Left Cornu Ammonis 3 (CA3) volume was a positive predictor of peer victimization (all, p \u3c 0.013). Left CA3 volume was a positive predictor of WM and left Cornu Ammonis 4 (CA4) volume negatively predicted WM (all, p \u3c 0.025). A cluster analysis revealed that children displaying symptoms of hyperactivity-impulsivity are the most at risk for peer victimization. Interventions focusing on minimizing peer victimization may aid in mitigating adverse downstream effects, and assist in promoting brain health and cognitive function

School\u27s out: Parenting stress and screen time use in school-age children during the COVID-19 pandemic

Background During the COVID-19 pandemic, millions of children abruptly moved to online schooling, which required high levels of parental involvement. Family routines were disrupted, potentially increasing parental stress, and may be reflected in greater media screen time use in children. Objectives To determine whether (1) parenting styles and (2) parenting stress were associated with children\u27s screen time use during the pandemic compared to the pre-pandemic period. Methods Parents (\u3e 18 years of age) were recruited to complete an online survey regarding changes in their children\u27s (6–12 years) screen time use and daily activities before and during the pandemic. Stress and parental involvement were assessed using the Perceived Stress Scale (PSS) and Alabama Parenting Questionnaires respectively. General linear models assessed whether parenting style and parent stress were associated with children\u27s screen time during the pandemic, adjusting for demographic variables and daily activities. Results 104 parents were enrolled, and 73 (70.2%) parents completed the surveys. Children\u27s screen time (e.g., watching television and playing video games) increased significantly, from 2.6 to 5.9h a day (p =.001) during pandemic-related school closures. Fewer changes in children\u27s screen time use were significantly associated with greater parental involvement (p =.017). Parent stress (p =.018) significantly predicted children\u27s screen time use. Lower household income was associated with increased hours of screen time in both models (both, p \u3c.05). Conclusions: Children\u27s screen time increased significantly during the initial months of the pandemic. Parent stress and parenting styles may be modifiable risk factors to promote children\u27s well-being during the ongoing pandemic

Amygdala subnuclei development in adolescents with autism spectrum disorder: Association with social communication and repetitive behaviors

Introduction: The amygdala subnuclei regulate emotional processing and are widely implicated in social cognitive impairments often seen in children with autism spectrum disorder (ASD). Dysregulated amygdala development has been reported in young children with ASD; less is known about amygdala maturation in later adolescence, a sensitive window for social skill development. Methods: The macrostructural development of the amygdala subnuclei was assessed at two time points in a longitudinal magnetic resonance imaging (MRI) study of adolescents with ASD (n = 23) and typically-developing adolescents (n = 15). In adolescents with ASD, amygdala subnuclei growth was assessed in relation to ASD symptomatology based on standardized diagnostic assessments. Participants were scanned with MRI at median age of 12 years and returned for a second scan at a median age of 15 years. The volumes of nine amygdala subnuclei were extracted using an automatic segmentation algorithm. Results: When examining the longitudinal data acquired across two time points, adolescents with ASD had larger basolateral amygdala (BLA) nuclei volumes compared to typically developing adolescents (B = 46.8, p = 0.04). When examining ASD symptomatology in relation to the growth of the amygdala subnuclei, reciprocal social interaction scores on the ADI-R were positively associated with increased growth of the BLA nuclei (B = 8.3, p \u3c 0.001). Growth in the medial nucleus negatively predicted the communication (B = −46.9, p = 0.02) and social (B = −47.7, p \u3c 0.001) domains on the ADOS-G. Growth in the right cortical nucleus (B = 26.14, p = 0.02) positively predicted ADOS-G social scores. Central nucleus maturation (B = 29.9, p = 0.02) was associated with the repetitive behaviors domain on the ADOS-G. Conclusions: Larger BLA volumes in adolescents with ASD may reflect underlying alterations in cellular density previously reported in post-mortem studies. Furthermore, findings demonstrate an association between regional growth in amygdala subnuclei volumes and ASD symptomatology. Improved understanding of the developmental trajectories of the amygdala subnuclei may aid in identifying key windows for interventions, particularly for social communication, in adolescents with ASD

Amygdala subnuclei volumes and anxiety behaviors in children and adolescents with autism spectrum disorder, attention deficit hyperactivity disorder, and obsessive–compulsive disorder

Alterations in the structural maturation of the amygdala subnuclei volumes are associated with anxiety behaviors in adults and children with neurodevelopmental and associated disorders. This study investigated the relationship between amygdala subnuclei volumes and anxiety in 233 children and adolescents (mean age = 11.02 years; standard deviation = 3.17) with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and children with obsessive compulsive disorder (OCD), as well as typically developing (TD) children. Parents completed the Child Behavior Checklist (CBCL), and the children underwent structural MRI at 3 T. FreeSurfer software was used to automatically segment the amygdala subnuclei. A general linear model revealed that children and adolescents with ASD, ADHD, and OCD had higher anxiety scores compared to TD children (p \u3c.001). A subsequent interaction analysis revealed that children with ASD (B = 0.09, p \u3c.0001) and children with OCD (B = 0.1, p \u3c.0001) who had high anxiety had larger right central nuclei volumes compared with TD children. Similar results were obtained for the right anterior amygdaloid area. Amygdala subnuclei volumes may be key to identifying children with neurodevelopmental disorders or those with OCD who are at high risk for anxiety. Findings may inform the development of targeted behavioral interventions to address anxiety behaviors and to assess the downstream effects of such interventions

Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation

Sorting of endocytic ligands and receptors is critical for diverse cellular processes. The physiological significance of endosomal sorting proteins in vertebrates, however, remains largely unknown. Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc) and thus is required for the proper delivery of iron to erythroid progenitors. Snx3 is highly expressed in vertebrate hematopoietic tissues. Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates due to impaired transferrin (Tf)-mediated iron uptake and its accumulation in early endosomes. This impaired iron assimilation can be complemented with non-Tf iron chelates. We show that Snx3 and Vps35, a component of the retromer, interact with Tfrc to sort it to the recycling endosomes. Our findings uncover a role of Snx3 in regulating Tfrc recycling, iron homeostasis, and erythropoiesis. Thus, the identification of Snx3 provides a genetic tool for exploring erythropoiesis and disorders of iron metabolism.National Institutes of Health (U.S.) (P01 HL032262

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Effects of Early Embryonic Alcohol Exposure on Activity Patterns in Zebrafish (Danio rerio)

SFWT Zebrafish were exposed to various concentrations of EtOH at 24 hours post-fertilization for a period of two hours. When fish reached maturity they were placed in individual tanks in a larger open field. A preliminary strain comparison was also conducted using control (EtOH untreated) SFWT and AB fish. The behaviour of fish was recorded for 24 hours during a normal light:dark cycle. Motor patterns and general activity were quantified and analyzed and several behaviors were found to change significantly throughout the daytime and nighttime period. Also, fish exposed to the highest concentration of alcohol were found to exhibit significantly reduced amount of thrashing towards other subjects as compared to fish in the control group confirming previous results that demonstrated reduction of shoaling after early embryonic alcohol exposure.MAS

Effects of Early Embryonic Ethanol Exposure on Adult Zebrafish Social Behavior

The purpose of this thesis was two-fold: 1) to investigate preferences for various aspects of social stimuli in adult zebrafish, and 2) to investigate whether low-dose embryonic alcohol exposure affected how zebrafish responded to these various social stimuli. Control fish were exposed to different behavioral paradigms to measure responses to and preferences for various social and predator stimuli. Both male and female fish were found to prefer all-male shoals to all-female and mixed shoals, and zebrafish were able to reliably discriminate between larger shoals when ratios of 2 vs. 1 were employed. Fish avoided a moving predator image, and an elongated image of a zebrafish, which resembles a predator, and did not display a preference for yellow or red coloured fish images over control images. To test for the effects of embryonic ethanol exposure, zebrafish eggs were submerged in low concentrations of ethanol for a period of 2 hours at 24 hours post-fertilization and were tested during adulthood (4 months old onwards). Control and alcohol-exposed fish were placed in different behavioral paradigms that measured their responses to social and predator stimuli. It was found that zebrafish exposed to low doses of ethanol at 24 hours post-fertilization do not demonstrate robust differences in comparison to non-exposed control fish for any of the behaviors measured. Overall, the findings present zebrafish responses to various social stimuli, and suggest that low-dose ethanol exposure does not robustly affect social responses.Ph.D.2019-07-11 00:00:0

Early adversity and positive parenting: Association with cognitive outcomes in children with autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and repetitive behaviors. Children with ASD are statistically more likely to experience early adversity; however, little is known about the types of early adversity that place these children at risk, the role of parenting as a protective factor, and how this early life stress impacts cognitive outcomes. We assessed early adversity in 302 children (ASD = 98) aged 6–16 years old, using parent-based report. To identify protective factors, we assessed parenting styles using parent surveys. Executive functions were assessed in the children using the WISC-V. Children with ASD had an increased incidence of familial stressors compared to the typically developing (TD) group. Positive parenting was associated with a significant decrease in the incidence of familial adverse events for both children with ASD and TD children. Examining the relationship between adversity and cognitive outcomes, in young children (6–11 years) with ASD, environmental stressors were associated with cognitive impairments. Findings suggest children with ASD may be at higher risk for familial adversity than their TD peers. However, all children benefit from positive parenting styles, which may mitigate the adverse effects of family-based early life stress. Lay Summary: Some key features of Autism Spectrum Disorder (ASD) include difficulties with communication and social impairments. This means that children with ASD may be more likely to experience early adversity (stressful social interactions which take place during childhood) than children without ASD. Research in typically developing (TD) children has shown that experiencing more stressful events in childhood can cause changes in the brain, which can potentially impact the child\u27s memory, reasoning, and decision-making skills later in life. However, there is evidence to suggest that having a nurturing relationship with a parent can offset some of the negative impacts of childhood adversity. In our study, we found that children with ASD are more likely to experience family-related stress compared to TD children. Having a positive relationship with a parent, however, was linked to experiencing this type of stress less often for all children, regardless of whether they were diagnosed with ASD. We also found that stressors related to environmental factors like financial instability were associated with lower cognitive abilities in children with ASD under 12 years of age. Understanding how these factors interact and differ in children with ASD can help to build stronger families and help children with ASD to thrive throughout their development

School's out: parenting stress and screen time use in school-age children during the COVID-19 pandemic

Background: During the COVID-19 pandemic, millions of children abruptly moved to online schooling, which required high levels of parental involvement. Family routines were disrupted, potentially increasing parental stress, and may be reflected in greater media screen time use in children. Objectives: To determine whether 1) parenting styles and 2) parenting stress were associated with children’s screen time use during the pandemic compared to the pre-pandemic period. Methods: Parents (&gt;18 years of age) were recruited to complete an online survey regarding changes in their children’s (6-12 years) screen time use and daily activities before and during the pandemic. Stress and parental involvement were assessed using the Perceived Stress Scale (PSS) and Alabama Parenting Questionnaires respectively. General linear models assessed whether parenting style and parent stress was associated with children’s screen time during the pandemic, adjusting for demographic variables and daily activities. Results: 104 parents were enrolled, and 78 (75%) parents completed the surveys. Children’s screen time (e.g., watching television and playing video games) increased significantly, from 2.6 hours to 5.8 hours a day (p=.001) during pandemic-related school closures. Smaller changes in children’s screen time use were significantly associated with more parental involvement (p=.017). Parent stress (p=.018) significantly predicted children’s screen time use. Lower household income was associated with increased hours of screen time in both models (both, p&lt;.05). Conclusions: Children’s screen time nearly doubled during the initial months of the pandemic. Parent stress and parenting styles may be modifiable risk factors to promote children’s wellbeing during the ongoing pandemic