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

Abstract

BackgroundAnxiety 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.MethodsEighty-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.ResultsIn 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.ConclusionsEarly-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.

“Don’t judge me!”: Links between in vivo attention bias toward a potentially critical judge and fronto-amygdala functional connectivity during rejection in adolescent girls

“…Aligning with hypotheses, girls who attended more to a potentially critical judge relative to a positive judge during the AST also showed more positive coupling between the right amygdala and bilateral anterior PFC while receiving social rejection feedback on the Chatroom task. Interestingly, similar prior research has implicated the right amygdala specifically (e.g., Gee et al, 2013 ; Price et al, 2016 ; Abend et al, 2020 ), which could suggest meaningful lateralization. However, lateralized effects could also be related to inadvertent effects from data analysis ( Murphy et al, 2020 ).…”

“…On the other hand, less negative fronto-amygdala connectivity during threat processing may place children and adolescents at risk for anxiety. A substantive literature has linked youth anxiety to altered fronto-amygdala connectivity while viewing negative emotional stimuli (e.g., Monk et al, 2008 ; Strawn et al, 2012 ; Campbell-Sills et al, 2011 ; White et al, 2017 ; Abend et al, 2020 ). Much of this research suggests that youth with anxiety show less negative coupling (or more positive coupling) between the amygdala (particularly the right amygdala) and regions of ventrolateral and medial PFC in response to social threat ( Monk et al, 2008 ; Davis et al, 2019 ) and non-social threat ( Strawn et al, 2012 ).…”

“…Much of this research suggests that youth with anxiety show less negative coupling (or more positive coupling) between the amygdala (particularly the right amygdala) and regions of ventrolateral and medial PFC in response to social threat ( Monk et al, 2008 ; Davis et al, 2019 ) and non-social threat ( Strawn et al, 2012 ). However, some studies have found associations between anxiety risk or anxiety symptoms in youth and greater negative connectivity between the amygdala and dorsolateral PFC when processing threats (e.g., Hardee et al, 2013 ; Abend et al, 2020 ). Many of these studies use the dot-probe task ( MacLeod et al, 1986 ), a widely-used computer paradigm that uses stationary stimuli to assess attention biases towards threatening stimuli, such as fearful faces, relative to more neutral stimuli.…”

Behavioral Inhibition and Dual Mechanisms of Anxiety Risk: Disentangling Neural Correlates of Proactive and Reactive Control

“…Thus, there may be multiple pathways through which a child can develop problems with anxiety, and it could be the case that each pathway/subtype is associated with a different profile of cognitive control dynamics. Previous neuroimaging work has demonstrated that cognitive-control-related neural activity differentiates BI and non-BI anxious youth (Abend et al, 2020; Smith et al, 2019), suggesting that cognitive control could serve as a potential criterion for defining anxious subtypes. However, the present study is the first to characterize how proactive and reactive control each uniquely relate to these pathways/subtypes.…”

Mapping the Specific Pathways to Early-Onset Mental Health Disorders: The “Watch Me Grow for REAL” Study Protocol

“…Evidence for the association between learning and the development of child psychopathology come from three main areas of research. First, it is well-established that an attentional bias towards aversive facial stimuli (e.g., angry and fear faces) have been linked to the development of anxiety disorders in children (37,(84)(85)(86). Second, children with ASD and conduct problems have difficulties with learning from emotional expressions (87).…”