Background: Genetic factors contribute to the development of anxiety disorders, yet few risk genes have been previously identified. One genomic approach that has achieved success in identifying risk genes in related childhood neuropsychiatric conditions is investigations of de novo variants, which has yet to be leveraged in childhood anxiety disorders.Methods: We performed whole-exome DNA sequencing in 76 parent-child trios (68 trios after quality control) recruited from a childhood anxiety disorder clinic and compared rates of rare and ultra-rare de novo variants with 790 previously sequenced control trios (783 trios after quality control). We then explored overlap with risk genes for other neuropsychiatric conditions and enrichment in biologic pathways.Results: Rare and ultra-rare de novo likely gene disrupting and predicted damaging missense genetic variants are enriched in anxiety disorder probands compared with controls (rare variant rate ratio 1.97, 95% confidence interval [CI]: 1.11-3.34, p = .03; ultra-rare variant rate ratio 2.59, 95% CI: 1.35-4.70, p = .008). These de novo damaging variants occur in individuals with a variety of childhood anxiety disorders and impact genes that have been associated with other neuropsychiatric conditions.Exploratory network analyses reveal enrichment of deleterious variants in canonical biological pathways.Conclusions: These findings provide a path for identifying risk genes and promising biologic pathways in childhood anxiety disorders by de novo genetic variant detection. Our results suggest the discovery potential of applying this approach in larger anxiety disorder cohorts to advance our understanding of the underlying biology of these common and debilitating conditions.

Humans influence each other's emotions. The spread of emotion is well documented across behavioral, psychophysiological, and neuroscientific levels of analysis, but might this influence also be evident in language (e.g., are people more likely to use emotion words after hearing someone else use them)? The current study tests whether mothers and children influence each other's use of affective language. From 2018 to 2020, children aged 6-12 who met diagnostic criteria for anxiety disorders and their mothers (N = 93 dyads) completed a challenging puzzle task while being video recorded. Analyses of transcriptions revealed that mothers and children indeed influenced each other's language. Bidirectional influence was observed for use of negative affect words: Mothers were more likely to use negative affect words if their child had just used negative affect words (over and above mothers' own language on their previous turn), and children were similarly influenced by mother affect word use. A similar bidirectional relation emerged for linguistic distance, a measure related to effective emotion regulation and mental health. However, the significance of the child-tomother direction of influence for these two variables varied depending on correction threshold and should thus be verified in future research. Nonetheless, these findings extend understanding of emotional influence by showing turn-by-turn relations between the use of affective language.

The COVID-19 pandemic has caused pervasive disruptions to family life. In light of the established role of parent-child dynamics in the maintenance of pediatric anxiety, we conducted a multilevel, multimodal study to examine how family-level factors moderate anxious youths’ responses to the COVID-19 pandemic. Prior to the pandemic (“pre-pandemic”), children with anxiety disorders (n = 28; ages 6-12) completed an fMRI task probing parental modulation of amygdala reactivity to fearful faces. During the first peak of the COVID-19 pandemic (“mid-pandemic”), parents completed questionnaires about their family’s exposure to COVID-19-related stress, their child’s COVID-19-related fears and behaviors, and their own (parental) functioning. Pre-pandemic parental modulation of amygdala reactivity moderated the association between children’s exposure to COVID-19-related stress and their COVID-19-related fears and behaviors. Furthermore, greater mid-pandemic parental assistance with their child’s use of venting and with their child’s use of expressive suppression as emotion regulation strategies exacerbated the effects of COVID-19-related stress on children’s COVID-19-related fears and behaviors, respectively. These results provide preliminary insight into the ways in which distinct family-level factors may buffer or exacerbate the effects of COVID-19-related stress on youth with a history of anxiety disorders.

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