Faculty Bibliography

OBJECTIVE:Previous research has demonstrated that the amygdala is enlarged in children with autism spectrum disorder (ASD). However, the precise onset of this enlargement during infancy, how it relates to later diagnostic behaviors, whether the timing of enlargement in infancy is specific to the amygdala, and whether it is specific to ASD (or present in other neurodevelopmental disorders, such as fragile X syndrome) are all unknown. METHODS:Longitudinal MRIs were acquired at 6-24 months of age in 29 infants with fragile X syndrome, 58 infants at high likelihood for ASD who were later diagnosed with ASD, 212 high-likelihood infants not diagnosed with ASD, and 109 control infants (1,099 total scans). RESULTS:Infants who developed ASD had typically sized amygdala volumes at 6 months, but exhibited significantly faster amygdala growth between 6 and 24 months, such that by 12 months the ASD group had significantly larger amygdala volume (Cohen's d=0.56) compared with all other groups. Amygdala growth rate between 6 and 12 months was significantly associated with greater social deficits at 24 months when the infants were diagnosed with ASD. Infants with fragile X syndrome had a persistent and significantly enlarged caudate volume at all ages between 6 and 24 months (d=2.12), compared with all other groups, which was significantly associated with greater repetitive behaviors. CONCLUSIONS:This is the first MRI study comparing fragile X syndrome and ASD in infancy, demonstrating strikingly different patterns of brain and behavior development. Fragile X syndrome-related changes were present from 6 months of age, whereas ASD-related changes unfolded over the first 2 years of life, starting with no detectable group differences at 6 months. Increased amygdala growth rate between 6 and 12 months occurs prior to social deficits and well before diagnosis. This gradual onset of brain and behavior changes in ASD, but not fragile X syndrome, suggests an age- and disorder-specific pattern of cascading brain changes preceding autism diagnosis.

BACKGROUND:Bacterial pneumonia is a major risk factor for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Pseudomonas aeruginosa (PA), an opportunistic pathogen with an increasing resistance acquired against multiple drugs, is one of the main causative agents of ALI and ARDS in diverse clinical settings. Given the anti-inflammatory role of the cannabinoid-2 receptor (CB2R), the effect of CB2R activation in the regulation of PA-induced ALI and inflammation was tested in a mouse model as an alternative to conventional antibiotic therapy. METHODS:In order to activate CB2R, a selective synthetic agonist, JWH133, was administered intraperitoneally (i.p.) to C57BL/6J mice. Furthermore, SR144528 (a selective CB2R antagonist) was administered in combination with JWH133 to test the specificity of the CB2R-mediated effect. PA was administered intratracheally (i.t.) for induction of pneumonia in mice. At 24 h after PA exposure, lung mechanics were measured using the FlexiVent system. The total cell number, protein content, and neutrophil population in the bronchoalveolar lavage fluid (BALF) were determined. The bacterial load in the whole lung was also measured. Lung injury was evaluated by histological examination and PA-induced inflammation was assessed by measuring the levels of BALF cytokines and chemokines. Neutrophil activation (examined by immunofluorescence and immunoblot) and PA-induced inflammatory signaling (analyzed by immunoblot) were also studied. RESULTS:CB2R activation by JWH133 was found to significantly reduce PA-induced ALI and the bacterial burden. CB2R activation also suppressed the PA-induced increase in immune cell infiltration, neutrophil population, and inflammatory cytokines. These effects were abrogated by a CB2R antagonist, SR144528, further confirming the specificity of the CB2R-mediated effects. CB2R-knock out (CB2RKO) mice had a significantly higher level of PA-induced inflammation as compared to that in WT mice. CB2R activation diminished the excess activation of neutrophils, whereas mice lacking CB2R had elevated neutrophil activation. Pharmacological activation of CB2R significantly reduced the PA-induced NF-κB and NLRP3 inflammasome activation, whereas CB2KO mice had elevated NLRP3 inflammasome. CONCLUSION/CONCLUSIONS:Our findings indicate that CB2R activation ameliorates PA-induced lung injury and inflammation, thus paving the path for new therapeutic avenues against PA pneumonia.

AIM/OBJECTIVE:Adolescents in low-and-middle-income countries (LMICs) are facing numerous developmental, sexual and reproductive health (SRH) challenges including exposure to multidimensional violence. Gender-based violence (GBV) specifically intimate partner violence (IPV) are both highly prevalent in LMICs and are strongly linked with poor SRH outcomes. However, GBV and IPV interventions have not yet been adequately integrated in SRH due to individual, social, cultural, service, and resource barriers. To promote long-term SRH, a more holistic approach that integrates GBV and IPV, and adolescent development needs is imperative. Digital health has the potential to address multiple service setup, provision, and addressing access barriers through designing and providing integrated SRH care. However, there are no guidelines for an integrated digital SRH and development promotion for adolescents in LMICs. METHODS:An umbrella review was conducted to synthesize evidence in three inter-related areas of digital health intervention literature: (i) SRH, (ii) GBV specifically IPV as a subset, and (iii) adolescent development and health promotion. We first synthesize findings for each area of research, then further analyze the implications and opportunities to inform approaches to develop an integrated intervention that can holistically address multiple SRH needs of adolescents in LMICs. Articles published in English, between 2010 and 2020, and from PubMed were included. RESULTS:Seventeen review articles met our review inclusion criterion. Our primary finding is that application of digital health strategies for adolescent SRH promotion is highly feasible and acceptable. Although effectiveness evidence is insufficient to make strong recommendations for interventions and best practices suggestions, some user-centered design guidelines have been proposed for web-based health information and health application design for adolescent use. Additionally, several digital health strategies have also been identified that can be used to further develop integrated GBV-IPV-SRH-informed services to improve adolescent health outcomes. We generated several recommendations and strategies to guide future digital based SRH promotion research from our review. CONCLUSIONS:Rigorous research that focuses on intervention effectiveness testing using a combination of digital health strategies and standardized albeit contextualized outcome measures would be important. Methodological improvement such as adoption of longitudinal experimental design will be crucial in generating evidence-based intervention and practice guidelines for adolescents in LMICs.

INTRODUCTION/UNASSIGNED:Clinical information regarding selective mutism (SM), a persistent and debilitating psychiatric disorder, in children is extremely limited. We aimed to examine sociodemographic characteristics and comorbid psychiatric conditions and identify clinical variables associated with sex and SM severity among children with SM. METHODS/UNASSIGNED:We analyzed the medical records of 49 children who received treatment for SM in four different tertiary hospitals in Turkey between 2016 and 2021. Children's charts were reviewed to examine clinical characteristics, comorbidities, and response to treatment. RESULTS/UNASSIGNED:= 0.039) than males. The vast majority of children received two or more psychiatric diagnoses. Children in the severe group had a longer duration of illness, higher rates of psychiatric comorbidity, speech delay, and treatment resistance. CONCLUSION/UNASSIGNED:Our study suggests that SM may have different clinical features according to sex and symptom severity of SM. More information about children with SM is needed to understand the development and maintenance of SM.

OBJECTIVES/OBJECTIVE:The Advance Premium Tax Credit (APTC) is designed to remedy lack of health insurance due to cost; however, approximately 30 million Americans remain without health insurance and millions of households leave billions in tax credits unclaimed each year. A prerequisite of APTC is to file one's taxes; however, few studies have examined tax filing and APTC jointly. This study examined the relationship between tax filing and applying for APTC, as well as perceived barriers to and sociodemographic characteristics associated with applying for the APTC. STUDY DESIGN/METHODS:Descriptive study. METHODS:Researchers surveyed 372 Marketplace-insured members who were eligible for APTC. RESULTS:Most of the sample filed personal taxes in 2019 and planned to file taxes in 2020, yet only 23% applied for the APTC in 2019, and 26.3% were planning to apply in 2020. Most commonly, respondents were not going to apply because they believed they were not eligible (53.5%), they did not know about the APTC (15.8%), and they did not know whether they were eligible (9.9%). Logistic regression modeling found that employment, income, and race were significantly associated with applying for the APTC. CONCLUSIONS:Barriers to applying for the APTC were unrelated to tax filing and were specific to a lack of knowledge about the APTC and eligibility. These results indicate the need to build knowledge and awareness of the APTC and eligibility and to target groups least likely to apply. Implications and future directions are discussed.

An enduring issue in the study of mental health is identifying developmental processes that explain how childhood characteristics progress to maladaptive forms. We examine the role that behavioral inhibition (BI) has on social anxiety (SA) during adolescence in 868 families of twins assessed at ages 8, 13, and 15 years. Multimodal assessments of BI and SA were completed at each phase, with additional measures (e.g., parenting stress) for parents and twins. Analyses were conducted in several steps: first, we used a cross-lagged panel model to demonstrate bidirectional paths between BI and SA; second a biometric Cholesky decomposition showed that both genetic and environmental influences on childhood BI also affect adolescent SA; next, multilevel phenotypic models tested moderation effects between BI and SA. We tested seven potential moderators of the BI to SA prediction in individual models and included only those that emerged as significant in a final conditional model examining predictors of SA. Though several main effects emerged as significant, only parenting stress had a significant interaction with BI to predict SA, highlighting the importance of environmental moderators in models examining temperamental effects on later psychological symptoms. This comprehensive assessment continues to build the prototype for such developmental psychopathology models.

Irritability, characterized by anger in response to frustration, is normative in childhood. While children typically show a decline in irritability from toddlerhood to school age, elevated irritability throughout childhood may predict later psychopathology. The current study (n = 78) examined associations between trajectories of irritability in early childhood (ages 2-7) and irritability in adolescence (age 12) and tested whether these associations are moderated by parenting behaviors. Results indicate that negative emotion socialization moderated trajectories of irritability - relative to children with low stable irritability, children who exhibited high stable irritability in early childhood and who had parents that exhibited greater negative emotion socialization behaviors had higher irritability in adolescence. Further, negative parental control behavior moderated trajectories of irritability - relative to children with low stable irritability, children who had high decreasing irritability in early childhood and who had parents who exhibited greater negative control behaviors had higher irritability in adolescence. In contrast, positive emotion socialization and control behaviors did not moderate the relations between early childhood irritability and later irritability in adolescence. These results suggest that both irritability in early childhood and negative parenting behaviors may jointly influence irritability in adolescence. The current study underscores the significance of negative parenting behaviors and could inform treatment.