The Heterogeneity of Anxious Phenotypes: Neural Responses to Errors in Treatment-Seeking Anxious and Behaviorally-Inhibited Youth

Objective Although behaviorally inhibited (BI) temperament predicts risk for anxiety, anxiety in BI may involve distinct neural responses to errors. The current study examines the relations between anxiety and neural correlates of error processing both in youths identified as BI in early childhood and in youths seeking treatment for an anxiety disorder. Method All participants underwent functional magnetic resonance imaging using a flanker task to assess responses to errors. A study in healthy subjects assessed test−retest reliability to inform analyses in two other samples. For one sample, a cohort of BI youths (Low BI, n = 28; High BI, n = 27) was followed into adolescence. For the other, participants were recruited based on the presence or absence of an anxiety disorder. Using identical methods in medication-free subjects, analyses compared relations between anxiety and error processing across the two samples. Results Error-processing exhibited acceptable reliability. Within a ventromedial − prefrontal−cortex (vmPFC) cluster, anxiety related to error processing only in youths whose early-life BI status was known. In the high BI group, anxiety related to reduced neural response to errors. No such associations manifested in treatment-seeking youths. Other analyses mapped relations between error-processing and anxiety in each sample on its own. However, only the vmPFC cluster statistically differentiated the neural correlates of anxiety in BI. Conclusion BI temperament may define a unique pathway into anxiety involving perturbed neural responding to errors. Although BI is a risk factor for later anxiety, the neural and associated features of anxiety in BI youths may differ from those in treatment-seeking youths.