Faculty Bibliography

Conventionally, nanocarriers are used to regulate the controlled release of therapeutic payloads. Increasingly, they can also be designed to have an intrinsic therapeutic effect. For example, a positively charged nanocarrier can bind damage-associated molecular patterns, inhibiting toll-like receptor (TLR) pathway activation and thus modulating inflammation. These nucleic acid-binding nanomaterials (NABNs), which scavenge pro-inflammatory stimuli, exist in diverse forms, ranging from soluble polymers to nanoparticles and 2D nanosheets. Unlike conventional drugs that primarily address inflammation symptoms, these NABPs target the upstream inflammation initiation pathway by removing the agonists responsible for inflammation. Many NABNs have demonstrated effectiveness in murine models of inflammatory diseases. However, these scavengers have not been systematically studied and compared within a single setting. Herein, we screen a subset of the most potent NABNs to define their relative efficiency in scavenging cell-free nucleic acids and inhibiting various TLR pathways. This study helps interpret existing in vivo results and provides insights into the future design of anti-inflammatory nanocarriers.

Prior studies reported mixed effects of the COVID-19 pandemic on the mental health of children and adolescents with ADHD, but they were mainly cross-sectional and without controls. To clarify the impact, we searched Web of Science, EMBASE, Medline, and PsychINFO until 18/11/2023 and conducted a systematic review of controlled longitudinal cohort studies (Prospero: CRD42022308166). The Newcastle-Ottawa scale was used to assess quality. We identified 6 studies. Worsening of mental health symptoms was more evident in ADHD or control group according to symptom considered and context. However, those with ADHD had more persistent elevated symptoms and remained an at-risk population. Sleep problems deteriorated more significantly in those with ADHD. Lower pre-COVID emotion regulation skills and greater rumination were associated with worse mental health outcomes, and longer screen time with poorer sleep. Quality was rated as low in most studies, mainly due to self-report outcome measures and no information on attrition rates. Despite these limitations, results suggest a predominantly negative impact on youths with ADHD and may guide clinical practice and policy.

OBJECTIVE/UNASSIGNED:An expert consensus approach was used to determine the adequacy of children's psychopharmacology and to examine whether adequacy varied by demographic or clinical characteristics. METHODS/UNASSIGNED:Data were from the baseline interview of 601 children, ages 6-12 years, who had visited one of nine outpatient mental health clinics and participated in the Longitudinal Assessment of Manic Symptoms study. Children and parents were interviewed with the Kiddie Schedule for Affective Disorders and Schizophrenia and the Service Assessment for Children and Adolescents to assess the child's psychiatric symptoms and lifetime mental health services use, respectively. An expert consensus approach informed by published treatment guidelines was used to determine the adequacy of children's psychotropic medication treatment. RESULTS/UNASSIGNED:Black children (compared with White children; OR=1.84, 95% CI=1.53-2.23) and those with anxiety disorders (vs. no anxiety disorder; OR=1.55, 95% CI=1.08-2.20) were more likely to receive inadequate pharmacotherapy; those whose caregivers had a bachelor's degree or more education (vs. those who had a high school education, general equivalency diploma, or less than high school education; OR=0.74, 95% CI=0.61-0.89) were less likely to receive inadequate pharmacotherapy. CONCLUSIONS/UNASSIGNED:The consensus rater approach permitted use of published treatment efficacy data and patient characteristics (e.g., age, diagnoses, history of recent hospitalizations, and psychotherapy) to assess adequacy of pharmacotherapy. These results replicate findings of racial disparities reported in previous research using traditional methods to determine treatment adequacy (e.g., with a minimum number of treatment sessions) and highlight the continued need for research on racial disparities and strategies to improve access to high-quality care.

Background: Children and adolescents who live in resource-limited communities in sub-Saharan Africa (SSA) experience significant mental health problems, including behavioral problems. In SSA, one of the most significant impediments to expanding services is a scarcity of mental health specialists. Task-shifting can effectively solve the mental health care gap in low-resource settings, yet it is underutilized in child and adolescent mental health. Moreover, the experiences of lay providers are understudied in global mental health, despite their potential impact on intervention effectiveness. In this study, we examined the experiences of community health workers and parent peers with the task-shifting of an evidence-based family strengthening intervention in Uganda. Methods: As part of a larger randomized clinical trial, semi-structured in-depth interviews were conducted with 24 facilitators selected using stratified purposive sampling. Interviews explored their decision to participate in the program; experiences with the training; and experiences with intervention delivery. All interviews were conducted in Luganda (local language) and audio recorded. They were transcribed verbatim and translated into English. Thematic analysis was used to analyze the data. Results: Despite concerns around lack of previous experience and time commitment, facilitators reported high relevance of the intervention to the families in their communities as well as their own as a motivation to participate. They also identified financial incentives as a motivating factor. These two factors also ensured their attendance at the training. They were satisfied with the content and skills provided during the training and felt prepared to deliver the intervention. During intervention delivery, they enjoyed seeing the families engaged and participating actively in the sessions as well as observing positive changes in the families. Some challenges with family attendance and engagement were noted. The facilitators reported an increased sense of self-efficacy and competence over time; and expressed high satisfaction with supervision. Conclusion: Facilitators"™ positive experiences point to the high acceptability and appropriateness of task-shifting this intervention in low-resource settings. As the global mental health field continues to be interested in task-shifting interventions to lay providers, successful examples should be studied so that evidence-based models can be put in place to support them through the process.

Schizophrenia is increasingly recognized as a disorder with altered integration between large-scale functional networks and cortical-subcortical pathways. This spatial long-distance information communication must be associated with white matter (WM) fiber bundles. With accumulating evidence that WM functional signals reflect the intrinsic neural activities, how the deep callosal organization modulates cortical functional activities through WM remains unclear in schizophrenia. Using a data-driven method, we identified nine WM and gray matter (GM) functional networks, and then parcellated corpus callosum into distinct sub-regions. Combining functional connectivity and fiber tracking analysis, we estimated the structural and functional connectivity changes of callosal-WM-cortical circuits in schizophrenia. We observed higher structural and functional connectivity between corpus callosum, WM and GM functional networks involving visual network (visual processing), executive control network (executive controls), ventral attention network (processing of salience), and limbic network (emotion processing) in schizophrenia compared to healthy controls. We also found nine abnormal pathways of callosal-WM-cortical circuits involving the above networks and default mode network (self-related thought). These results highlight the role of connectivity deficits in callosal-WM-cortical circuits may play in understanding the delusions, hallucinations and cognitive impairment of schizophrenia.

Children must learn specific motor actions to use everyday objects as their designers intended. However, designed actions are not obvious to children and often are difficult to implement. Children must know what actions to do and how to execute them. Previous work identified a protracted developmental progression in learning designed actions-from nondesigned exploratory actions, to display of the designed action, to successful implementation. Presumably, caregivers can help children to overcome the challenges in discovering and implementing designed actions. Mothers of 12-, 18- to 24-, and 30- to 36-month-olds (N = 74) were asked to teach their children to open containers with twist-off or pull-off lids. Mothers' manual and verbal input aligned with the developmental progression and with children's actions in the moment, pointing to the role of attuned social information in helping children learn to use objects for activities of daily living. However, mothers sometimes "overhelped" by implementing designed actions for children instead of getting children to do it themselves, highlighting the challenges of teaching novices difficult motor actions.

BACKGROUND:The co-occurrence between attention-deficit hyperactivity disorder (ADHD) and physical conditions is frequent but often goes unrecognised. Most available evidence on the links between ADHD and physical conditions relies on cross-sectional studies. Understanding temporal sequences of associations is key to inform appropriate treatment and preventive strategies. We aimed to assess possible longitudinal associations between ADHD symptoms and a broad range of physical conditions, adjusting for several confounding factors. METHODS:Participants came from the population-based Quebec Longitudinal Study of Child Development. Participants were selected from the Quebec Birth Registry, recruited between October, 1997, and July, 1998, from the province of Quebec, Canada, and followed up in early childhood (n=2120; age 5 months-5 years), middle childhood (n=1750; age 6-12 years), and adolescence (n=1573; age 13-17 years). Main outcome measures included ADHD symptom severity and physical conditions, which were reported by the person most knowledgeable of the child in early childhood, by teachers in middle childhood, and self-reported in adolescence. Multivariable regression analyses were conducted to study the prospective associations between ADHD symptoms and later physical conditions, and physical conditions and later ADHD symptoms, adjusting for multiple confounders. FINDINGS/RESULTS:We found several prospective associations between ADHD symptoms and physical conditions including asthma, high BMI (≥1 SD above the mean), epilepsy, dental caries, acute infections, injuries, and sleep problems. After adjusting for key confounding factors, several associations remained: ADHD symptoms in early childhood were associated with later high BMI during middle childhood (odds ratio [OR] 1·19 [95% CI 1·05-1·35]) and adolescence (OR 1·14 [1·01-1·29]), and with unintentional injuries during adolescence (OR 1·10 [1·01-1·21]). ADHD symptoms in middle childhood were significantly associated with later dental caries during adolescence (OR 1·10 [1·01-1·20]). Unintentional injuries in early childhood were associated with later ADHD symptoms in middle childhood (standardised mean difference [SMD] 0·15 [0·05-0·24]) and adolescence (SMD 0·13 [0·04-0·23]), and restless legs syndrome symptoms in middle childhood were associated with later ADHD symptoms in adolescence (SMD 0·15 [0·05-0·25]). INTERPRETATION/CONCLUSIONS:Our results point to the need to carefully monitor children with ADHD in early or middle childhood for several physical conditions, and to monitor children with particular physical conditions for ADHD symptoms. Our study also calls for policies to promote more integrated health-care systems for children with complex mental and physical needs, bridging the current gap between mental and physical health-care services. FUNDING/BACKGROUND:Québec Government's Ministry of Health, Ministry of Education, and Ministry of Family Affairs; The Lucie and André Chagnon Foundation; the Robert-Sauvé Research Institute of Health and Safety at Work; the Québec Statistics Institute; the Fonds de Recherche du Québec-Santé; the Fonds de Recherche du Québec-Societé et Culture; Canada's Social Science and Humanities Research Council; the Canadian Institutes of Health Research, the Sainte-Justine Research Center; and the French National Research Agency. TRANSLATION/UNASSIGNED:For the French translation of the abstract see Supplementary Materials section.

BACKGROUND:Maternal stress has negative consequences on infant behavioral development, and COVID-19 presented uniquely stressful situations to mothers of infants born during the pandemic. We hypothesized that mothers with higher levels of perceived stress during the pandemic would report higher levels of infant regulatory problems including crying and interrupted sleep patterns. METHODS:As part 6 sites of a longitudinal study, mothers of infants born during the pandemic completed the Perceived Stress Scale, the Brief Infant Sleep Questionnaire, and an Infant Crying survey at 6 (n = 433) and 12 (n = 344) months of infant age. RESULTS:Maternal perceived stress, which remained consistent at 6 and 12 months of infant age, was significantly positively correlated with time taken to settle infants. Although maternal perceived stress was not correlated with uninterrupted sleep length, time taken to put the infant to sleep was correlated. Perceived stress was also correlated with the amount of infant crying and fussiness reported at 6 months. CONCLUSIONS:Mothers who reported higher levels of perceived stress during the pandemic reported higher levels of regulatory problems, specifically at 6 months. Examining how varying levels of maternal stress and infant behaviors relate to overall infant developmental status over time is an important next step. IMPACT/CONCLUSIONS:Women giving birth during the COVID-19 pandemic who reported higher levels of stress on the Perceived Stress Scale also reported higher levels of infant fussiness and crying at 6 months old, and more disruptive sleep patterns in their infants at 6 months and 12 months old. Sleeping problems and excessive crying in infancy are two regulatory problems that are known risk factors for emotional and behavioral issues in later childhood. This paper is one of the first studies highlighting the associations between maternal stress and infant behaviors during the COVID-19 pandemic.

OBJECTIVE:The association between attention-deficit/hyperactivity disorder (ADHD) and shorter height is unclear. This study examined the risk of shorter height in individuals with ADHD, and the influence of prenatal factors, ADHD medication, psychiatric comorbidity, socioeconomic factors and familial liability. METHOD/METHODS:We draw on Swedish National Registers for two different study designs. First, height data for 14,268 individuals with ADHD and 71,339 controls were stratified into two groups: 1: Before and 2: After stimulant treatment were introduced in Sweden. Second, we used a family-based design including 833,172 relatives without ADHD with different levels of relatedness to the individuals with ADHD and matched controls. RESULTS:ADHD was associated with shorter height both before (below average height: OR=1.31, 95 % CI=1.22-1.41) and after (below average height: OR=1.21, 95 % CI=1.13-1.31) stimulants for ADHD were introduced in Sweden and was of similar magnitude in both cohorts. The association between ADHD and shorter height attenuated after adjustment for prenatal factors, psychiatric disorders and SES. Relatives of individuals with ADHD had an increased risk of shorter height (below average height in full siblings: OR=1.14, 95 % CI=1.09-1.19; maternal half siblings: OR=1.10, 95 % CI=1.01-1.20; paternal half siblings: OR=1.15, 95 % CI=1.07-1.24, first full cousins: OR=1.10, 95 % CI=1.08-1.12). CONCLUSION/CONCLUSIONS:Our findings suggest that ADHD is associated with shorter height. On a population level, this association was present both before and after ADHD-medications were available in Sweden. The association between ADHD and height was partly explained by prenatal factors, psychiatric comorbidity, low SES and a shared familial liability for ADHD.