The Salience Network’s Role in the Association Between Intolerance of Uncertainty and Anxiety in Adolescents

Anxiety disorders are highly prevalent in children and adolescents and are they cause of with considerable impairment at home, in school, and with friends. Intolerance of uncertainty (IU), or the inability to tolerate distress resulting from ambiguity, is one factor known to contribute to the development and maintenance of anxiety. The salience network (SN) is one brain pathway thought to underlie IU and anxiety, as dysfunction in this network has been observed in those with high IU and those with anxiety disorders. The current study utilized data collected as part of an NIMH-funded neuroimaging study of adolescents (ages 12-14, n=78) presenting with mild to severe anxiety. During this study, adolescents completed self-report measures of IU (Intolerance of Uncertainty Scale – Child Version), and anxiety (Screen for Anxiety Related Disorders), a clinical interview (Anxiety Disorders Interview Schedule), and a resting state fMRI scan. Fifty-three participants contributed usable clinical and scan data. Scan data were analyzed using CONN-fMRI Functional Connectivity Toolbox v18b. Statistical analyses were completed in SPSS; moderation analyses were completed using PROCESS for SPSS software. Regression analysis was used to relate IU to anxiety symptoms. Brain analyses associating IU with SN iFC and anxiety with SN iFC were completed. SN iFC was extracted and used as a moderator in regression analyses of IU predicting anxiety. Finally, several secondary analyses were completed, including SN whole brain analysis, and moderation analyses using the SN as a moderator on the associations between the two subfactors of IU, inhibitory IU and prospective IU, and children’s anxiety symptoms. Results supported that hypothesis that IU was related to children’s anxiety symptoms; however, no other hypotheses were supported. SN connectivity was not related to children’s IU, anxiety, or on the association between. These null results may have occurred for several reasons. First, an IU-related construct may have been a better predictor of anxiety than IU in this sample. Second, brain regions outside of the SN may contribute more to child IU and anxiety than those in the SN. Third, the study may have been underpowered to detect a moderation effect using brain data in anxious youth

Neurobiological Correlates of Language Deficits and Emotion Dysregulation in Children with Severe Temper Outbursts

The goal of this study was to investigate the relationships among foundational language abilities, social uses of language, emotion regulation, and functional connectivity of language networks in young children (ages 5-9 years old) exhibiting a range of emotion dysregulation. Previous literature suggests that expressive language skills are critical for emotion regulation as they provide a socially appropriate means for communicating needs, regulating actions, and providing an understanding of one’s emotional environment and that these skills may be associated with developmental changes within language networks. Thus, the current study predicted that deficits in emotion regulation ability would be associated with basic and social language deficits and that these deficits would be associated with alterations in functional connectivity in the language networks. Results of the current study indicate that dimensional communication deficits in both basic and social language are related to difficulties in emotion regulation, however, these were not found within the study groups. Further, only deficits in social communication ability were related to neurobiological alterations in Broca’s area in children with STO compared to children with ADHD. This suggests that children with STO are not unique in their social communication difficulties and that social communication accounts for greater differences in neurobiological abnormalities in Broca’s area networks than does emotion regulation

Early life stress, prenatal secondhand smoke exposure, and the development of internalizing symptoms across childhood

Abstract Background Prior findings relating secondhand tobacco smoke (SHS) exposure and internalizing problems, characterized by heightened anxiety and depression symptoms, have been equivocal; effects of SHS on neurodevelopment may depend on the presence of other neurotoxicants. Early life stress (ELS) is a known risk factor for internalizing symptoms and is also often concurrent with SHS exposure. To date the interactive effects of ELS and SHS on children’s internalizing symptoms are unknown. We hypothesize that children with higher exposure to both prenatal SHS and ELS will have the most internalizing symptoms during the preschool period and the slowest reductions in symptoms over time. Methods The present study leveraged a prospective, longitudinal birth cohort of 564 Black and Latinx mothers and their children, recruited between 1998 and 2006. Cotinine extracted from cord and maternal blood at birth served as a biomarker of prenatal SHS exposure. Parent-reported Child Behavior Checklist (CBCL) scores were examined at four timepoints between preschool and eleven years-old. ELS exposure was measured as a composite of six domains of maternal stress reported at child age five. Latent growth models examined associations between SHS, ELS, and their interaction term with trajectories of children’s internalizing symptoms. In follow-up analyses, weighted quintile sum regression examined contributions of components of the ELS mixture to children’s internalizing symptoms at each time point. Results ELS interacted with SHS exposure such that higher levels of ELS and SHS exposure were associated with more internalizing symptoms during the preschool period (β = 0.14, p = 0.03). The interaction between ELS and SHS was also associated with a less negative rate of change in internalizing symptoms over time (β=-0.02, p = 0.01). Weighted quintile sum regression revealed significant contributions of maternal demoralization and other components of the stress mixture to children’s internalizing problems at each age point (e.g., age 11 WQS β = 0.26, p < 0.01). Conclusions Our results suggest that prior inconsistencies in studies of SHS on behavior may derive from unmeasured factors that also influence behavior and co-occur with exposure, specifically maternal stress during children’s early life. Findings point to modifiable targets for personalized prevention

Assessing harmonized intelligence measures in a multinational study

Studies examining the neurocognitive and circuit-based etiology of psychiatric illness are moving toward inclusive, global designs. A potential confounding effect of these associations is general intelligence; however, an internationally validated, harmonized intelligence quotient (IQ) measure is not available. We describe the procedures used to measure IQ across a five-site, multinational study and demonstrate the harmonized measure’s cross-site validity. Culturally appropriate intelligence measures were selected: four short-form Wechsler intelligence tests (Brazil, Netherlands, South Africa, United States) and the Binet Kamat (India). Analyses included IQ scores from 255 healthy participants (age 18–50; 42% male). Regression analyses tested between-site differences in IQ scores, as well as expected associations with sociodemographic factors (sex, socioeconomic status, education) to assess validity. Harmonization (e.g., a priori selection of tests) yielded the compatibility of IQ measures. Higher IQ was associated with higher socioeconomic status, suggesting good convergent validity. No association was found between sex and IQ at any site, suggesting good discriminant validity. Associations between higher IQ and higher years of education were found at all sites except the United States. Harmonized IQ scores provide a measure of IQ with evidence of good validity that can be used in neurocognitive and circuit-based studies to control for intelligence across global sites

Convergent neural correlates of prenatal exposure to air pollution and behavioral phenotypes of risk for internalizing and externalizing problems: potential biological and cognitive pathways

© 2022 Elsevier Ltd. All rights reserved.Humans are ubiquitously exposed to neurotoxicants in air pollution, causing increased risk for psychiatric outcomes. Effects of prenatal exposure to air pollution on early emerging behavioral phenotypes that increase risk of psychopathology remain understudied. We review animal models that represent analogues of human behavioral phenotypes that are risk markers for internalizing and externalizing problems (behavioral inhibition, behavioral exuberance, irritability), and identify commonalities among the neural mechanisms underlying these behavioral phenotypes and the neural targets of three types of air pollutants (polycyclic aromatic hydrocarbons, traffic-related air pollutants, fine particulate matter < 2.5 µm). We conclude that prenatal exposure to air pollutants increases risk for behavioral inhibition and irritability through distinct mechanisms, including altered dopaminergic signaling and hippocampal morphology, neuroinflammation, and decreased brain-derived neurotrophic factor expression. Future studies should investigate these effects in human longitudinal studies incorporating complex exposure measurement methods, neuroimaging, and behavioral characterization of temperament phenotypes and neurocognitive processing to facilitate efforts aimed at improving long-lasting developmental benefits for children, particularly those living in areas with high levels of exposure.This work was supported by the National Institutes of Environmental Health Sciences R01ES030950, R01ES032296 and K23026239 to A.E.M. and Whole Communities Whole Health, a University of Texas at Austin Grand Challenge Initiative (OVPR) to F.A.C.info:eu-repo/semantics/publishedVersio