Threat-anticipatory psychophysiological response is enhanced in youth with anxiety disorders and correlates with prefrontal cortex neuroanatomy

Background Threat anticipation engages neural circuitry that has evolved to promote defensive behaviours; perturbations in this circuitry could generate excessive threat-anticipation response, a key characteristic of pathological anxiety. Research into such mechanisms in youth faces ethical and practical limitations. Here, we use thermal stimulation to elicit pain-anticipatory psychophysiological response and map its correlates to brain structure among youth with anxiety and healthy youth. Methods Youth with anxiety (n = 25) and healthy youth (n = 25) completed an instructed threat-anticipation task in which cues predicted nonpainful or painful thermal stimulation; we indexed psychophysiological response during the anticipation and experience of pain using skin conductance response. High-resolution brain-structure imaging data collected in another visit were available for 41 participants. Analyses tested whether the 2 groups differed in their psychophysiological cue-based pain-anticipatory and pain-experience responses. Analyses then mapped psychophysiological response magnitude to brain structure. Results Youth with anxiety showed enhanced psychophysiological response specifically during anticipation of painful stimulation (b = 0.52, p = 0.003). Across the sample, the magnitude of psychophysiological anticipatory response correlated negatively with the thickness of the dorsolateral prefrontal cortex (p(FWE) < 0.05); psychophysiological response to the thermal stimulation correlated positively with the thickness of the posterior insula (p(FWE) < 0.05). Limitations Limitations included the modest sample size and the cross-sectional design. Conclusion These findings show that threat-anticipatory psychophysiological response differentiates youth with anxiety from healthy youth, and they link brain structure to psychophysiological response during pain anticipation and experience. A focus on threat anticipation in research on anxiety could delineate relevant neural circuitry.

Automated summary

The study investigates pain-anticipatory psychophysiological response in youth with anxiety and healthy youth using thermal stimulation. The results show that youth with anxiety exhibit enhanced psychophysiological response during the anticipation of painful stimulation, and this response is correlated with specific brain structures. Specifically, thinner dorsolateral prefrontal cortex thickness is associated with stronger anticipatory response, while thicker posterior insula thickness is associated with stronger response to thermal stimulation.