Fear responses to safety cues in anxious adolescents: Preliminary evidence for atypical age-associated trajectories of functional neural circuits

Abstract

Adolescent anxiety is common and impairing and often persists into adulthood. There is growing evidence that adult anxiety is characterized by abnormal fear responses to threat and safety cues, along with perturbations in fear-related neural circuits. Although some of this work has been extended to adolescents, with promising results, it is not yet clear whether changes in these circuits across developmental age varies between anxious and non-anxious adolescents. Here we used fMRI to examine how age modulates neural responses as adolescents are exposed to threat and safety cues. Participants were 15 anxious and 11 non-anxious adolescents (age 12-17) who completed a fear conditioning paradigm. The paradigm incorporated a threat cue comprising a neutral face which was paired with a fearful, screaming face, a safety cue comprising a different neutral face, and a control stimulus. Across the whole sample, neural activation to the threat cue (relative to the control cue) correlated positively with age in a number of regions, including the dorsal anterior cingulate and bilateral dorsolateral prefrontal cortex (PFC). However, neural activation to the safety cue (relative to the control cue) was modulated differently by age in the two groups: a more positive association between activation and age was observed in the control group compared to the anxious group in various regions including medial and dorsolateral PFC, anterior insula, and amygdala. These findings suggest that maturation of the neural substrates of fear responses to safety cues may be perturbed in anxious adolescents, potentially contributing to the emergence and maintenance of anxiety disorders in adulthood.

Convergent individual differences in visual cortices, but not the amygdala across standard amygdalar fMRI probe tasks

“…Our main contrast of interest for this task was the comparison between CS+ (unmatched) vs CS−, following previous studies that have reported AMG recruitment, mainly in adolescents, but in adult populations as well (Lau et al, 2011). This contrast has also been reported to engage other brain regions (Haddad et al, 2015). We cannot determine whether this lack of overall recruitment was due to habituation across our imaging session or if it was a task effect.…”

“…We did not test for correlations with the SLp because it did not successfully recruit the AMG, contrary to previous results in the literature (Haddad et al, 2015; Lau et al, 2008). Our main contrast of interest for this task was the comparison between CS+ (unmatched) vs CS−, following previous studies that have reported AMG recruitment, mainly in adolescents, but in adult populations as well (Lau et al, 2011).…”

Annual Research Review: An expanded account of information‐processing mechanisms in risk for child and adolescent anxiety and depression

“…Studies of youth anxiety report greater conditioned fear responses to the CS+ in anxious children and adolescents relative to nonanxious peers, although there are some inconsistencies across measures (skin conductance responses (SCR); verbal fear ratings; Britton et al., ; Craske, Waters, Craske, Bergman, & Treanor, ; Lau et al., ; Waters, Henry, & Neumann, ). Responses to the CS− during acquisition are also higher in anxious compared with nonanxious youth (Britton et al., ; Craske, Waters, et al., ; Haddad, Bilderbeck, James, & Lau, ; Waters et al., ). One study did not find group differences (Pliszka, Hatch, Borcherding, & Rogeness, ) though this investigated anxiety in attention‐deficit hyperactivity disorder children, and another study found that group differences emerged in the absence of fear discrimination to the CS+ versus CS− in anxious children only (Liberman, Lipp, Spence, & March, ).…”

Extinction learning in childhood anxiety disorders, obsessive compulsive disorder and post-traumatic stress disorder: implications for treatment

“…In these studies, differential conditioning is [71,76,77]. Although, some studies suggest that anxious youth show larger SCR and SR fear to both the CS+ and the CS-, a larger differential response is not reported [41,72,74,75]. Consistent with clinical evidence, anxious youth have been found to exhibit greater behavioral avoidance, as evidenced by higher rates of study attrition when confronted with an aversive US [41,73].…”

“…Additionally, anxiety symptom severity was found to be associated with greater SR fear of stimuli [73]. As noted above for unaffected youth, several factors have been found to influence threat conditioning, including gender [78] and age-related neurobiological distinctions [75]. Unfortunately, there has been no examination of threat generalization or context conditioning in anxious youth.…”