{"doi":"10.1503/jpn.200110","title":"Threat-anticipatory psychophysiological response is enhanced in youth with anxiety disorders and correlates with prefrontal cortex neuroanatomy","abstract":"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 (pFWE < 0.05); psychophysiological response to the thermal stimulation correlated positively with the thickness of the posterior insula (pFWE < 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.","journal":"Journal of Psychiatry and Neuroscience","year":2021,"id":173214,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":398596,"name":"Mira Bajaj","orcid":null,"position":1,"is_corresponding":false},{"id":295776,"name":"Anita Harrewijn","orcid":"0000-0001-9938-4048","position":2,"is_corresponding":false},{"id":398597,"name":"Chika Matsumoto","orcid":null,"position":3,"is_corresponding":false},{"id":79177,"name":"Kalina J. Michalska","orcid":"0000-0002-4830-5036","position":4,"is_corresponding":false},{"id":487144,"name":"Elizabeth A. Necka","orcid":"0000-0002-9749-5710","position":5,"is_corresponding":false},{"id":710382,"name":"Esther E. Palacios‐Barrios","orcid":"0000-0002-6988-652X","position":6,"is_corresponding":false},{"id":37376,"name":"Ellen Leibenluft","orcid":"0000-0001-8971-2087","position":7,"is_corresponding":false},{"id":304288,"name":"Lauren Y. Atlas","orcid":"0000-0001-5693-4169","position":8,"is_corresponding":false},{"id":72962,"name":"Daniel S. Pine","orcid":"0000-0002-4301-9516","position":9,"is_corresponding":false},{"id":298724,"name":"Rany Abend","orcid":"0000-0003-0022-3418","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-18T23:46:45.768135Z","pmid":"33703868","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}