Responding to threat: Associations between neural reactivity to and behavioral avoidance of threat in pediatric anxiety.

BACKGROUND: Despite broad recognition of the central role of avoidance in anxiety, a lack of specificity in its operationalization has hindered progress in understanding this clinically significant construct. The current study uses a multimodal approach to investigate how specific measures of avoidance relate to neural reactivity to threat in youth with anxiety disorders. METHODS: Children with anxiety disorders (ages 6-12 years; n = 65 for primary analyses) completed laboratory task- and clinician-based measures of avoidance, as well as a functional magnetic resonance imaging task probing neural reactivity to threat. Primary analyses examined the ventral anterior insula (vAI), amygdala, and ventromedial prefrontal cortex (vmPFC). RESULTS: Significant but distinct patterns of association with task- versus clinician-based measures of avoidance emerged. Clinician-rated avoidance was negatively associated with right and left vAI reactivity to threat, whereas laboratory-based avoidance was positively associated with right vAI reactivity to threat. Moreover, left vAI-right amygdala and bilateral vmPFC-right amygdala functional connectivity were negatively associated with clinician-rated avoidance but not laboratory-based avoidance. LIMITATIONS: These results should be considered in the context of the restricted range of our treatment-seeking sample, which limits the ability to draw conclusions about these associations across children with a broader range of symptomatology. In addition, the limited racial and ethnic diversity of our sample may limit the generalizability of findings. CONCLUSION: These findings mark an important step towards bridging neural findings and behavioral patterns using a multimodal approach. Advancing understanding of behavioral avoidance in pediatric anxiety may guide future treatment optimization by identifying individual-specific targets for treatment.

Affective language spreads between anxious children and their mothers during a challenging puzzle task.

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-to-mother 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. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Whole-exome DNA sequencing in childhood anxiety disorders identifies rare de novo damaging coding variants.

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.