Satisfaction with social connectedness is associated with depression and anxiety symptoms in neurodiverse first-semester college students.

LAY ABSTRACT: How satisfied people feel with their social connections and support is related to mental health outcomes for many different types of people. People may feel less socially connected at some times in their life-like when they start college. Feeling disconnected from others could lead to depression or anxiety. The transition to college may be especially difficult for autistic students as they are more likely to have difficulties adjusting socially. In our study, we asked 263 college students to answer questions about their emotions and social satisfaction twice per week during their first semester of college. We found that students who reported being less satisfied with their social connectedness (either at the beginning or throughout the semester) tended to express more symptoms of depression and anxiety. This relationship between social satisfaction and anxiety was even stronger for people who had a strong desire for social interaction (i.e. were more socially motivated). Students with more autistic traits tended to report more mood concerns, and they also reported being less satisfied with friendships at the beginning of the semester. This information may help to support ongoing efforts to better address mental health in autistic college students by encouraging efforts to improve social satisfaction.

Repetitive Negative Thinking As a Transdiagnostic Prospective Predictor of Depression and Anxiety Symptoms in Neurodiverse First-Semester College Students.

Background: Improving the understanding and treatment of mental health concerns, including depression and anxiety, are significant priorities for autistic adults. While several theories have been proposed to explain the high prevalence of internalizing symptoms in autistic populations, little longitudinal research has been done to investigate potential causal mechanisms. Additional research is needed to explore how proposed contributors to depression from general population research predict and/or moderate the development of internalizing symptoms in autistic individuals. In this study, we investigated the relation of one established risk factor, repetitive negative thinking (RNT), to internalizing symptoms over the course of college students' first semester, additionally examining whether this association is moderated by a measure of autistic traits. Methods: Students were recruited from 4 northeastern U.S. universities: 144 participating students included 97 nonautistic students and 47 participants who either reported a formal autism diagnosis (n = 15) or endorsed a history of self and/or others thinking that they may be autistic (n = 32). Participants completed a baseline survey battery within their first 2 weeks of starting college, a brief biweekly survey throughout their first semester (up to 24 times across 12 weeks), and an endpoint packet. Results: Elevated trait-like RNT at baseline was prospectively associated with biweekly ratings of depression and anxiety symptoms across the semester. In addition, greater RNT was synchronously related to elevated sadness, anhedonia, and anxiety throughout the semester. Contrary to hypotheses, a shorter term predictive relationship between RNT at one timepoint and mood symptoms at the next was largely unsupported. While these patterns were observed across neurotypes, students with higher self-reported autistic traits were more likely to experience RNT, as well as depressive and anxiety symptoms. Conclusions: These preliminary findings highlight RNT as a specific mechanism that may be a useful prevention and/or intervention target toward reducing the elevated depression and anxiety rates in the autistic community.

Why was this study done?: Many autistic people have depression and anxiety. However, we know very little about why autistic people are more likely to have these mental health concerns than people who are not autistic. We also do not know what leads to these symptoms over time. One theory is that repetitive negative thinking (RNT; or thinking repeatedly about problems and worries) might cause depression and anxiety. Autistic people might do more RNT than nonautistic people. What was the purpose of this study?: In this study, we wanted to see how RNT might relate to depression and anxiety over the first semester of college. We looked at how this might be related to autistic traits. What did the researchers do?: The researchers gave surveys to 144 students about their experiences with depression, anxiety, and RNT. The participants answered these surveys at the beginning and end of their first semester at their university. They also completed a brief survey 24 times (twice per week for 12 weeks) during the semester. What were the results of the study?: We found that overall RNT levels at the beginning of the semester were related to sadness, anhedonia (lack of pleasure), and anxiety later. In-the-moment RNT reported on the twice-weekly survey was also related to sadness, anhedonia, and anxiety. However, RNT on biweekly surveys did not seem to predict mood symptoms a few days later. Students with higher levels of autistic traits tended to report more depression and anxiety, as well as more RNT. What do these findings add to what was already known?: This study helps us to understand that RNT might be related to depression and anxiety, regardless of whether or not someone is autistic. This might mean that reducing RNT could help prevent or treat depression and anxiety, especially in autistic adults. What are potential weaknesses in the study?: Our study had a low number of participants with formal autism diagnoses (15 people), so it might not represent the broader population of autistic adults with formal diagnoses as well as we would like. Nevertheless, we had a larger group with self-reported or suspected autism (32 people). How will these findings help autistic adults now or in the future?: These findings help us to better understand risk factors for depression and anxiety in autistic adults. Since RNT was related to depression and anxiety in the same way regardless of levels of autistic traits in our study, we hope that clinicians will feel more comfortable providing therapy to people with mood disorders, regardless of whether they are autistic and/or have high autistic traits. This could be a small step toward increasing equity and accessibility of mental health services for autistic adults.

Maternal stress and early childhood BMI among US children from the Environmental influences on Child Health Outcomes (ECHO) program.

BACKGROUND: We aimed to understand the association between maternal stress in the first year of life and childhood body mass index (BMI) from 2 to 4 years of age in a large, prospective United States-based consortium of cohorts. METHODS: We used data from the Environmental influences on Child Health Outcomes program. The main exposure was maternal stress in the first year of life measured with the Perceived Stress Scale (PSS). The main outcome was the first childhood BMI percentile after age 2 until age 4 years. We used an adjusted linear mixed effects model to examine associations between BMI and PSS quartile. RESULTS: The mean BMI percentile in children was 59.8 (SD 30) measured at 3.0 years (SD 1) on average. In both crude models and models adjusted for maternal BMI, age, race, ethnicity, infant birthweight, and health insurance status, no linear associations were observed between maternal stress and child BMI. CONCLUSIONS: Among 1694 maternal-infant dyads, we found no statistically significant relationships between maternal perceived stress in the first year of life and child BMI after 2 through 4 years. IMPACT: Although existing literature suggests relationships between parental stress and childhood BMI, we found no linear associations between maternal stress in the first year of life and childhood BMI at 2-4 years of age among participants in ECHO cohorts. Higher maternal stress was significantly associated with Hispanic ethnicity, Black race, and public health insurance. Our analysis of a large, nationally representative sample challenges assumptions that maternal stress in the first year of life, as measured by a widely used scale, is associated with offspring BMI.

Model-estimated impacts of pediatric respiratory syncytial virus prevention programs in Mali on asthma prevalence.

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in young children and is associated with subsequent recurrent wheezing illness and asthma (wheeze/asthma). RSV prevention may therefore reduce wheeze/asthma prevalence. Objectives: We estimated the contribution of RSV LRTI and the impact of RSV prevention on recurrent wheeze/asthma in Mali. Methods: We simulated 12 consecutive monthly birth cohorts in Mali and estimated RSV LRTI cases through 2 years and recurrent wheeze/asthma prevalence at 6 years under different RSV prevention scenarios: status quo, seasonal birth-dose extended half-life mAb, and seasonal birth-dose extended half-life mAb followed by 2 doses of pediatric vaccine (mAb + vaccine). We used World Health Organization (WHO) Preferred Product Characteristics for RSV prevention, demographic and RSV epidemiologic data from Mali, regional recurrent wheeze/asthma prevalence, and relative risk of recurrent wheeze/asthma given early childhood RSV LRTI. Results: Among the simulated cohort of 778,680 live births, 10.0% had RSV LRTI by 2 years and 89.6% survived to 6 years. We estimated that 13.4% of all recurrent wheeze/asthma at 6 years was attributable to RSV LRTI. Recurrent wheeze/asthma prevalence at 6 years was 145.0 per 10,000 persons (RSV LRTI attributable) and 1084.2 per 10,000 persons (total). In mAb and mAb + vaccine scenarios, RSV LRTI cases decreased by 11.8% and 44.4%, respectively, and recurrent wheeze/asthma prevalence decreased by 11.8% and 44.4% (RSV LRTI attributable) and 1.6% and 5.9% (total). Conclusion: In Mali, RSV prevention programs may have a meaningful impact on chronic respiratory disease, strengthening the case for investment in RSV prevention.

Seeing the impossible: Visualizing latent variable models with flexplavaan.

Latent variable models (LVMs) are incredibly flexible tools that allow users to address research questions they might otherwise never be able to answer (McDonald, 2013). However, one major limitation of LVMs is evaluating model fit. There is no universal consensus about how to evaluate model fit, either globally or locally. Part of the reason evaluating these models is difficult is because fit is typically reduced to a handful of statistics that may or may not reflect the model's adequacy and/or assumptions. In this article we argue that proper evaluation of model fit must include visualizing both the raw data and the model-implied fit. Visuals reveal, at a glance, the fit of the model and whether the model's assumptions have been met. Unfortunately, tools for visualizing LVMs have historically been limited. In this article, we introduce new plots and reframe existing plots that provide necessary resources for evaluating LVMs. These plots are available in a new open-source R package called flexplavaan, which combines the model plotting capabilities of flexplot with the latent variable modeling capabilities of lavaan. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Prospective Relations between Parents' Depressive Symptoms and Children's Attributional Style.

Children of parents with depression are at increased risk for developing psychopathology. The purpose of the current longitudinal study was to examine the dynamic relations between parents' depressive symptoms and children's cognitions, specifically their attributions for the causes of life events. Participants were 227 parent-child dyads with one parent (Mage = 42.19, SD = 6.82; 76% female) and one child (Mage = 12.53, SD = 2.33; 53% female) per family. Parents either were diagnosed with a current major depressive disorder (n= 129; 72.9% female) or were lifetime-free of mood disorders (n= 98; 79.6% female). The Beck Depression Inventory-II was used to obtain a dimensional measure of parents' depressive symptoms, and the Children's Attributional Style Questionnaire-Revised was used to assess children's attributions of negative and positive events. Evaluations were conducted 5 times across 22 months. We used latent difference score (LDS) modeling to examine the relations between changes in parents' depressive symptoms and changes in children's attributional style over time. The final model provided a close fit to the data: χ2(30) = 35.22, p = .24; comparative fit index = .995, root mean square error of approximation = .028, 90% confidence interval (CI) [.000, .060], standardized root mean square residual = .024. Parents' levels of depressive symptoms significantly predicted the worsening of children's attributions (i.e., becoming more pessimistic) over the 22 months, whereas children's attributions did not significantly predict changes in parents' depressive symptoms at the next time point. Preventive interventions should aim to both reduce parents' depression and teach children strategies for examining the accuracy of their beliefs regarding the causes of life events.

Assessing the strength of evidence for a causal effect of respiratory syncytial virus lower respiratory tract infections on subsequent wheezing illness: a systematic review and meta-analysis.

BACKGROUND: Although a positive association has been established, it is unclear whether lower respiratory tract infections (LRTIs) with respiratory syncytial virus (RSV) cause chronic wheezing illnesses. If RSV-LRTI were causal, we would expect RSV-LRTI prevention to reduce the incidence of chronic wheezing illnesses in addition to reducing acute disease. We aimed to evaluate the strength of evidence for a causal effect of RSV-LRTI on subsequent chronic wheezing illness to inform public health expectations for RSV vaccines. METHODS: We did a systematic review and meta-analysis of observational studies evaluating the association between RSV-LRTI and subsequent wheezing illness (exposure studies) and studies evaluating the association between RSV immunoprophylaxis and subsequent wheezing illness (immunoprophylaxis studies). Exposure studies were included if the exposure group members had an LRTI with laboratory-confirmed RSV and if the exposure ascertainment period began before 2 years of age and ended before 5 years of age. We required a wash-out period of more than 30 days between the index RSV-LRTI and the outcome measurement to allow for resolution of the acute illness. Comparisons between RSV-LRTI and non-RSV-LRTI were not included. Immunoprophylaxis studies were included if they measured the association with subsequent wheezing illness relative to a control group, either in a randomised controlled trial (RCT) or an observational design. For the immunoprophylaxis drugs in question, we required evidence of efficacy in targeting RSV-LRTI from at least one RCT to ensure biological plausibility. All variations of wheezing illness were combined into a single outcome that refers broadly to asthma or any other respiratory illness with wheezing symptoms. Ovid MEDLINE and Embase databases were searched from inception up to Aug 28, 2018. We evaluated whether data from exposure studies could provide evidence against the most viable non-causal theory that RSV-LRTI is a marker of respiratory illness susceptibility rather than a causal factor. Additionally, we tested whether RSV immunoprophylaxis reduces the odds of subsequent wheezing illnesses. We used a random-effects modelling framework and, to accommodate studies providing multiple correlated estimates, robust variance estimation meta-regressions. Meta-regression coefficients (b) quantify differences between exposure and comparator groups on the loge odds ratio (loge OR) scale. FINDINGS: From 14 235 records we identified 57 eligible articles that described 42 studies and provided 153 effect estimates. 35 studies estimated the direct effect of RSV-LRTI on wheezing illnesses (exposure studies) and eight evaluated the effect of RSV immunoprophylaxis (immunoprophylaxis studies). Exposure studies that adjusted for genetic influences yielded a smaller mean adjusted OR estimate (aOR+ 2·45, 95% CI 1·23-4·88) compared with those that did not (4·17, 2·36-7·37), a significant difference (b 0·53, 95% CI 0·04-1·02). Infants who were not protected with RSV immunoprophylaxis tended to have higher odds of subsequent wheezing illness, as we would expect if RSV-LRTI were causal, but the effect was not significant (OR+ 1·21, 95% CI 0·73-1·99). There was generally a high threat of confounding bias in the observational studies. Additionally, in both the observational studies and immunoprophylaxis RCTs, there was high risk of bias due to missing outcome data. INTERPRETATION: Our findings, limited to exposure and immunoprophylaxis studies, do not support basing policy decisions on an assumption that prevention of RSV-LRTI will reduce recurrent chronic wheezing illnesses. FUNDING: Bill & Melinda Gates Foundation.

Effects of an adolescent depression prevention program on maternal criticisms and positive remarks.

This study examined effects of an adolescent depression prevention program on maternal criticisms and positive remarks, whether the extent of adolescents' depression accounted for effects, and whether effects of the program on maternal criticisms and positive remarks differed by adolescents' gender. Participants were 298 adolescent (Mage = 14.79, SD = 1.36; 59% female) offspring of mothers with histories of depression; youth were randomized to either a cognitive-behavioral prevention (CBP) program or usual care (UC). At baseline and 9-month postintervention evaluations, mothers were administered the Five-Minute Speech Sample to measure number of criticisms and positive remarks made during an open-ended description of their child and their relationship. Adolescents' depression from pre- through postintervention was assessed with interviews. A hierarchical generalized linear model showed a significant condition-by-gender interaction, indicating that, controlling for baseline criticism, at postintervention mothers of girls in CBP made significantly more criticisms than did mothers of girls in UC, whereas mothers of boys in CBP made fewer criticisms than did mothers of boys in UC. The extent of adolescents' depression from pre- through postintervention partially mediated the relation between intervention condition and mothers' criticisms, for boys but not for girls. Second, controlling for preintervention positive remarks, at postintervention, mothers of youth in CBP made significantly more positive remarks about their child than did mothers of youth in UC, regardless of gender; this relation was not mediated by adolescent depression from pre- through postintervention. We suggest possible explanations for the observed effects of CBP on mothers' criticisms and positive remarks. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12-13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies.

Depression and Anxiety Symptoms in Female Adolescents: Relations with Parental Psychopathology and Parenting Behavior.

Parental psychopathology and parenting behavior are known to be related to adolescents depression and anxiety, but unique roles of mothers and fathers are not clear. Our aim was to examine the relation of maternal and paternal psychopathology, emotional support, and respect for autonomy, and their interaction to depression and anxiety symptoms in adolescents. In total, 142 female adolescents participated, together with 138 mothers and 113 fathers. Data were analyzed using latent growth curve modeling. Paternal emotional support was negatively related to adolescent baseline level of depression and anxiety symptoms. Further, we found that there was a positive association between respect for autonomy and depression symptoms in adolescents for higher levels of paternal symptoms of psychological problems.

The effect of content and tone of maternal evaluative feedback on self-cognitions and affect in young children.

Feedback that young children receive from others can affect their emotions and emerging self-views. The current experiment tested the effect of negative content (criticism) and negative tone (hostile) of the feedback on children's affect, self-evaluations, and attributions. We also explored whether maternal history of depression and children's temperament moderated these relations. Participants were 152 mothers and children (48% girls) aged 4 and 5 years (M = 61.6 months, SD = 6.83). The task involved three scenarios enacted by dolls; a child doll made something (e.g., picture, house, numbers) that had a mistake (e.g., no windows on the house) and proudly showed it to the mother doll, who then gave feedback (standardized, audio recorded) to the child. Children were randomized to one of four maternal feedback conditions: negative or neutral content in either a negative or neutral tone. Negative content (criticism) produced significantly more negative affect and lower self-evaluations than neutral content. When the tone of the feedback was hostile, children of mothers who had been depressed during the children's lifetimes were significantly more likely to make internal attributions for mistakes than children of nondepressed mothers. In addition, among children with low temperamental negative affectivity, in the presence of negative tone, negative content significantly predicted more internal attributions for the errors. Findings are discussed in terms of understanding the role of evaluative feedback in children's emerging social cognitions and affect.

Practical and Conceptual Considerations for the Primary Prevention of Asthma.

Asthma is among the most common chronic diseases worldwide and is a significant contributor to the global health burden, highlighting the urgent need for primary prevention. This article outlines several practical and conceptual challenges that accompany primary prevention efforts. It advocates for improved predictive modeling to identify those at high-risk of developing asthma using automated algorithms within electronic medical records systems and explanatory modeling to refine understanding of causal pathways. Understanding the many issues that are likely to affect the success of primary prevention efforts helps the community of individuals invested in asthma prevention organize efforts and maximize their impact.

Sex-specific association between prenatal life stress exposure and infant pro-inflammatory cytokine levels during acute respiratory infection.

BACKGROUND: Prenatal life stress exposure is linked to dysregulated immune function and chronic inflammatory disease in offspring, but we know little about its effects on infant immune response during viral infection. METHOD: To address this issue, we examined associations between prenatal life stress exposure and infant upper-airway inflammatory markers during acute respiratory infection (ARI) using data from a prospective, population-based birth-cohort study (N = 180). Infant inflammation was measured as a continuous latent factor within a structural equation modeling framework using nasal wash concentrations of interleukin-1ß, interleukin-6, and tumor necrosis factor-α. We hypothesized that infants exposed to prenatal life stress would have greater levels of nasal inflammation during ARI and increased risk for ARI-related morbidity in early childhood. RESULTS: Our findings contradicted these hypotheses and provided evidence of sexually dimorphic effects of prenatal stress exposure on infant immune functioning during ARI. Among boys, but not girls, prenatal stress was negatively associated with nasal inflammation and indirectly associated with both lower ARI severity and reduced likelihood of subsequent ARI-related hospitalization in the 2nd and 3rd years of life. CONCLUSION: These data suggest that prenatal stress exposure may be beneficial for infant boys in the context of respiratory viral infections; however, it will be critical to determine if these benefits are offset by increased risk for chronic inflammatory diseases in later childhood. As the participants in this cohort are being followed longitudinally through age 8, we will be able to evaluate long-term health outcomes in future studies.

Delineation of the Individual Effects of Vitamin E Isoforms on Early Life Incident Wheezing.

OBJECTIVES: To test the hypothesis that maternal plasma alpha-tocopherol levels are associated with protection from childhood wheeze and that this protection is modified by gamma-tocopherol. STUDY DESIGN: We conducted a prospective nested study in the Infant Susceptibility to Pulmonary Infections and Asthma Following Respiratory Syncytial Virus Exposure birth cohort of 652 children with postpartum maternal plasma vitamin E isoforms used as a surrogate for pregnancy concentrations. Our outcomes were wheezing and recurrent wheezing over a 2-year period, ascertained using validated questionnaires. We assessed the association of alpha- and gamma-tocopherol with wheezing outcomes using multivariable adjusted logistic regression, and tested for interaction between the isoforms with respect to the risk for wheezing outcomes. RESULTS: Children with wheezing (n = 547, n = 167; 31%) and recurrent wheezing (n = 545, n = 55; 10.1%) over a 2-year period were born to mothers with significantly lower postpartum maternal plasma concentrations of alpha-tocopherol, P = .016 and P = .007, respectively. In analyses of IQR increases, alpha-tocopherol was associated with decreased risk of wheezing (aOR 0.70 [95% CI 0.53,0.92]) and recurrent wheezing (aOR 0.63 [95% CI 0.42,0.95]). For gamma-tocopherol, the aOR for wheezing was 0.79 (95% CI 0.56-1.10) and the aOR for recurrent wheezing was 0.56 (95% CI 0.33-0.94, with nonmonotonic association). The association of alpha-tocopherol with wheezing was modified by gamma-tocopherol (P interaction = .05). CONCLUSIONS: Increases in postpartum maternal plasma alpha-tocopherol isoform concentrations were associated with decreased likelihood of wheezing over a 2-year period. Gamma-tocopherol modified this association.

Sex Differences in Vulnerability to Prenatal Stress: a Review of the Recent Literature.

PURPOSE OF REVIEW: To evaluate the degree to which recent studies provide evidence that the effects of prenatal maternal stress (PNMS) on child health outcomes vary depending on the child's biological sex. In this review, we used a broad definition of stress, including negative life events, psychological stress, and established stress biomarkers. We identified 50 peer-reviewed articles (published January 2015-December 2017) meeting the inclusion criteria. RECENT FINDINGS: Most articles (k = 35) found evidence of either sex-specific associations (significant in one sex but not the other) or significant PNMSxstress interactions for at least one child health outcome. Evidence for sex-dependent effects was strongest in the group of studies evaluating child neural/nervous system development and temperament as outcomes. There is sufficient evidence of sex-dependent associations to recommend that researchers always consider the potential role of child sex in PNMS programming studies and report descriptive statistics for study outcomes stratified by child biological sex.

Youth Cognitive-Behavioral Depression Prevention: Testing Theory in a Randomized Controlled Trial.

This study tested the plausibility of a theoretical model of change for the Penn Resiliency Program (PRP), a cognitive-behavioral (CB) depression prevention program for adolescents. Middle school students (N = 697) were randomized to PRP, an assessment-only control condition (CON), or a placebo-control condition (PLA). Explanatory style and depressive symptoms were evaluated over 24 months of follow-up. Relative to both CON and PLA, there were significant indirect effects of PRP on 12-month levels of depressive symptoms through improvements in explanatory style in two of three participating schools. Within a third school, where PRP was not effective in targeting depressive symptoms (Gillham et al., 2007), there was no evidence of group differences in growth in explanatory style or indirect effects. When effective, PRP's CB training provides incremental value over non-specific components and there are indirect effects on depressive symptoms through improvements in explanatory style.

Infant Viral Respiratory Infection Nasal Immune-Response Patterns and Their Association with Subsequent Childhood Recurrent Wheeze.

RATIONALE: Recurrent wheeze and asthma are thought to result from alterations in early life immune development following respiratory syncytial virus (RSV) infection. However, prior studies of the nasal immune response to infection have assessed only individual cytokines, which does not capture the whole spectrum of response to infection. OBJECTIVES: To identify nasal immune phenotypes in response to RSV infection and their association with recurrent wheeze. METHODS: A birth cohort of term healthy infants born June to December were recruited and followed to capture the first infant RSV infection. Nasal wash samples were collected during acute respiratory infection, viruses were identified by RT-PCR, and immune-response analytes were assayed using a multianalyte bead-based panel. Immune-response clusters were identified using machine learning, and association with recurrent wheeze at age 1 and 2 years was assessed using logistic regression. MEASUREMENTS AND MAIN RESULTS: We identified two novel and distinct immune-response clusters to RSV and human rhinovirus. In RSV-infected infants, a nasal immune-response cluster characterized by lower non-IFN antiviral immune-response mediators, and higher type-2 and type-17 cytokines was significantly associated with first and second year recurrent wheeze. In comparison, we did not observe this in infants with human rhinovirus acute respiratory infection. Based on network analysis, type-2 and type-17 cytokines were central to the immune response to RSV, whereas growth factors and chemokines were central to the immune response to human rhinovirus. CONCLUSIONS: Distinct immune-response clusters during infant RSV infection and their association with risk of recurrent wheeze provide insights into the risk factors for and mechanisms of asthma development.

A new model of wheezing severity in young children using the validated ISAAC wheezing module: A latent variable approach with validation in independent cohorts.

BACKGROUND: The International Study of Asthma and Allergies in Children (ISAAC) Wheezing Module is commonly used to characterize pediatric asthma in epidemiological studies, including nearly all airway cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) consortium. However, there is no consensus model for operationalizing wheezing severity with this instrument in explanatory research studies. Severity is typically measured using coarsely-defined categorical variables, reducing power and potentially underestimating etiological associations. More precise measurement approaches could improve testing of etiological theories of wheezing illness. METHODS: We evaluated a continuous latent variable model of pediatric wheezing severity based on four ISAAC Wheezing Module items. Analyses included subgroups of children from three independent cohorts whose parents reported past wheezing: infants ages 0-2 in the INSPIRE birth cohort study (Cohort 1; n = 657), 6-7-year-old North American children from Phase One of the ISAAC study (Cohort 2; n = 2,765), and 5-6-year-old children in the EHAAS birth cohort study (Cohort 3; n = 102). Models were estimated using structural equation modeling. RESULTS: In all cohorts, covariance patterns implied by the latent variable model were consistent with the observed data, as indicated by non-significant χ2 goodness of fit tests (no evidence of model misspecification). Cohort 1 analyses showed that the latent factor structure was stable across time points and child sexes. In both cohorts 1 and 3, the latent wheezing severity variable was prospectively associated with wheeze-related clinical outcomes, including physician asthma diagnosis, acute corticosteroid use, and wheeze-related outpatient medical visits when adjusting for confounders. CONCLUSION: We developed an easily applicable continuous latent variable model of pediatric wheezing severity based on items from the well-validated ISAAC Wheezing Module. This model prospectively associates with asthma morbidity, as demonstrated in two ECHO birth cohort studies, and provides a more statistically powerful method of testing etiologic hypotheses of childhood wheezing illness and asthma.

Identifying Moderators of Response to the Penn Resiliency Program: A Synthesis Study.

To identify moderators of a cognitive-behavioral depression prevention program's effect on depressive symptoms among youth in early adolescence, data from three randomized controlled trials of the Penn Resiliency Program (PRP) were aggregated to maximize statistical power and sample diversity (N = 1145). Depressive symptoms, measured with the Children's Depression Inventory (CDI; Kovacs 1992), were assessed at six common time points over two-years of follow-up. Latent growth curve models evaluated whether PRP and control conditions differed in the rate of change in CDI and whether youth- and family-level characteristics moderated intervention effects. Model-based recursive partitioning was used as a supplementary analysis for identifying moderators. There was a three-way interaction of PRP, initial symptom severity, and intervention site on growth in depressive symptoms. There was considerable variability in PRP's effects, with the nature of the interaction between PRP and initial symptom levels differing considerably across sites. PRP reduced depressive symptoms among youth with unmarried parents, but not among those with married parents. Finally, PRP's effects differed across school grade levels. Although initial symptom severity moderated PRP's effect on depressive symptoms, it was not a reliable indicator of how well the intervention performed, limiting its utility as a prescriptive variable. Our primary analyses suggest that PRP's effects are limited to youth whose parents are unmarried. The small number of fifth grade students (n = 25; 2 %) showed a delayed and sustained intervention response. Our findings underscore the importance of evaluating site, family, and contextual characteristics as moderators in future studies.