Levels of early-childhood behavioral inhibition predict distinct neurodevelopmental pathways to pediatric anxiety

Abstract

Background: Anxiety symptoms gradually emerge during childhood and adolescence. Individual differences in behavioral inhibition (BI), an early-childhood temperament, may shape developmental paths through which these symptoms arise. Cross-sectional research suggests that level of early-childhood BI moderates associations between later anxiety symptoms and threat-related amygdala-prefrontal cortex (PFC) circuitry function. However, no study has characterized these associations longitudinally. Here, we tested whether level of early-childhood BI predicts distinct evolving associations between amygdala-PFC function and anxiety symptoms across development.

Methods: Eighty-seven children previously assessed for BI level in early childhood provided data at ages 10 and/or 13 years, consisting of assessments of anxiety and an fMRI-based dot-probe task (including threat, happy, and neutral stimuli). Using linear-mixed-effects models, we investigated longitudinal changes in associations between anxiety symptoms and threat-related amygdala-PFC connectivity, as a function of early-childhood BI.

Results: In children with a history of high early-childhood BI, anxiety symptoms became, with age, more negatively associated with right amygdala-left dorsolateral-PFC connectivity when attention was to be maintained on threat. In contrast, with age, low-BI children showed an increasingly positive anxiety-connectivity association during the same task condition. Behaviorally, at age 10, anxiety symptoms did not relate to fluctuations in attention bias (attention bias variability, ABV) in either group; by age 13, low-BI children showed a negative anxiety-ABV association, whereas high-BI children showed a positive anxiety-ABV association.

Conclusions: Early-childhood BI levels predict distinct neurodevelopmental pathways to pediatric anxiety symptoms. These pathways involve distinct relations among brain function, behavior, and anxiety symptoms, which may inform diagnosis and treatment.

Trial registration: ClinicalTrials.gov NCT00018057.

Keywords: Amygdala; anxiety; attention; behavioral inhibition; children; connectivity; developmental; fMRI; prefrontal cortex.

Conflict of interest statement

Conflict of interest. None.

Figures

Fig. 1.

Associations between current anxiety symptoms and right amygdala–left DLPFC functional connectivity at ages 10 and 13 for the AC and AI task conditions and per BI group (Low BI, High BI). Each bar represents the slope estimate between SCARED scores and PPI β estimates for the respective group, task condition, and age. Asterisks within bars indicate slope estimates significantly different from 0; asterisks between bars indicate significant differences between slope estimates. Error bars indicate one standard error of the slope estimate. DLPFC, dorsolateral prefrontal cortex; SCARED, Screen for Child Anxiety Related Disorders; AC, angry-congruent; AI, angry-incongruent; BI, behavioral inhibition; PPI, psychophysiological interaction; *p < 0.05, **p < 0.01, ***p < 0.001.

Fig. 2.

Associations between current anxiety symptom severity and ABV scores at ages 10 and 13, in the low-BI and high-BI groups. Each bar represents the slope estimate between SCARED scores and ABV scores (averaged across angry-neutral and happy-neutral trials) collected at the same age. Asterisks within bars indicate slope estimates significantly different from 0; asterisks between bars indicate significant differences between slope estimates. Error bars indicate one standard error of the slope estimate. ABV, attention bias variability; BI, behavioral inhibition; SCARED, Screen for Child Anxiety Related Disorders; *p < 0.05, +p < 0.10.