Rany Abend1, Andrea L Gold2, Jennifer C Britton3, Kalina J Michalska4, Tomer Shechner5, Jessica F Sachs6, Anderson M Winkler7, Ellen Leibenluft7, Bruno B Averbeck8, Daniel S Pine7. 1. Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland. Electronic address: rany.abend@nih.gov. 2. Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island; Pediatric Anxiety Research Center, Bradley Hospital, Riverside, Rhode Island. 3. Department of Psychology, University of Miami, Coral Gables, Florida. 4. Department of Psychology, University of California Riverside, Riverside, California. 5. Psychology Department, University of Haifa, Haifa, Israel. 6. Medical College of Wisconsin, Wauwatosa, Wisconsin. 7. Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland. 8. Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
Abstract
BACKGROUND: While translational theories link neurodevelopmental changes in threat learning to pathological anxiety, findings from studies in patients inconsistently support these theories. This inconsistency may reflect difficulties in studying large patient samples with wide age ranges using consistent methods. A dearth of imaging data in patients further limits translational advances. We address these gaps through a psychophysiology and structural brain imaging study in a large sample of patients across the lifespan. METHODS: A total of 351 participants (8-50 years of age; 209 female subjects; 195 healthy participants and 156 medication-free, treatment-seeking patients with anxiety) completed a differential threat conditioning and extinction paradigm that has been validated in pediatric and adult populations. Skin conductance response indexed psychophysiological response to conditioned (CS+, CS-) and unconditioned threat stimuli. Structural magnetic resonance imaging data were available for 250 participants. Analyses tested anxiety and age associations with psychophysiological response in addition to associations between psychophysiology and brain structure. RESULTS: Regardless of age, patients and healthy comparison subjects demonstrated comparable differential threat conditioning and extinction. The magnitude of skin conductance response to both conditioned stimulus types differentiated patients from comparison subjects and covaried with dorsal prefrontal cortical thickness; structure-response associations were moderated by anxiety and age in several regions. Unconditioned responding was unrelated to anxiety and brain structure. CONCLUSIONS: Rather than impaired threat learning, pathological anxiety involves heightened skin conductance response to potential but not immediately present threats; this anxiety-related potentiation of anticipatory responding also relates to variation in brain structure. These findings inform theoretical considerations by highlighting anticipatory response to potential threat in anxiety. Published by Elsevier Inc.
BACKGROUND: While translational theories link neurodevelopmental changes in threat learning to pathological anxiety, findings from studies in patients inconsistently support these theories. This inconsistency may reflect difficulties in studying large patient samples with wide age ranges using consistent methods. A dearth of imaging data in patients further limits translational advances. We address these gaps through a psychophysiology and structural brain imaging study in a large sample of patients across the lifespan. METHODS: A total of 351 participants (8-50 years of age; 209 female subjects; 195 healthy participants and 156 medication-free, treatment-seeking patients with anxiety) completed a differential threat conditioning and extinction paradigm that has been validated in pediatric and adult populations. Skin conductance response indexed psychophysiological response to conditioned (CS+, CS-) and unconditioned threat stimuli. Structural magnetic resonance imaging data were available for 250 participants. Analyses tested anxiety and age associations with psychophysiological response in addition to associations between psychophysiology and brain structure. RESULTS: Regardless of age, patients and healthy comparison subjects demonstrated comparable differential threat conditioning and extinction. The magnitude of skin conductance response to both conditioned stimulus types differentiated patients from comparison subjects and covaried with dorsal prefrontal cortical thickness; structure-response associations were moderated by anxiety and age in several regions. Unconditioned responding was unrelated to anxiety and brain structure. CONCLUSIONS: Rather than impaired threat learning, pathological anxiety involves heightened skin conductance response to potential but not immediately present threats; this anxiety-related potentiation of anticipatory responding also relates to variation in brain structure. These findings inform theoretical considerations by highlighting anticipatory response to potential threat in anxiety. Published by Elsevier Inc.
Authors: M A Fullana; B J Harrison; C Soriano-Mas; B Vervliet; N Cardoner; A Àvila-Parcet; J Radua Journal: Mol Psychiatry Date: 2015-06-30 Impact factor: 15.992
Authors: Rany Abend; Diana Burk; Sonia G Ruiz; Andrea L Gold; Julia L Napoli; Jennifer C Britton; Kalina J Michalska; Tomer Shechner; Anderson M Winkler; Ellen Leibenluft; Daniel S Pine; Bruno B Averbeck Journal: Elife Date: 2022-04-27 Impact factor: 8.713
Authors: Anita Harrewijn; Elizabeth R Kitt; Rany Abend; Chika Matsumoto; Paola Odriozola; Anderson M Winkler; Ellen Leibenluft; Daniel S Pine; Dylan G Gee Journal: Behav Brain Res Date: 2020-11-04 Impact factor: 3.332
Authors: Anaïs F Stenson; Nicole R Nugent; Sanne J H van Rooij; Sean T Minton; Alisha B Compton; Rebecca Hinrichs; Tanja Jovanovic Journal: Dev Sci Date: 2020-07-28
Authors: Daniel M Stout; Susan Powell; Aileen Kangavary; Dean T Acheson; Caroline M Nievergelt; Taylor Kash; Alan N Simmons; Dewleen G Baker; Victoria B Risbrough Journal: Neurobiol Stress Date: 2021-06-26
Authors: Elizabeth R Steuber; Antonia V Seligowski; Alyssa R Roeckner; Mariam Reda; Lauren A M Lebois; Sanne J H van Rooij; Vishnu P Murty; Timothy D Ely; Steven E Bruce; Stacey L House; Francesca L Beaudoin; Xinming An; Donglin Zeng; Thomas C Neylan; Gari D Clifford; Sarah D Linnstaedt; Laura T Germine; Scott L Rauch; Christopher Lewandowski; Sophia Sheikh; Christopher W Jones; Brittany E Punches; Robert A Swor; Meghan E McGrath; Lauren A Hudak; Jose L Pascual; Anna M Chang; Claire Pearson; David A Peak; Robert M Domeier; Brian J O'Neil; Niels K Rathlev; Leon D Sanchez; Robert H Pietrzak; Jutta Joormann; Deanna M Barch; Diego A Pizzagalli; James M Elliott; Ronald C Kessler; Karestan C Koenen; Samuel A McLean; Kerry J Ressler; Tanja Jovanovic; Nathaniel G Harnett; Jennifer S Stevens Journal: J Psychiatr Res Date: 2021-07-14 Impact factor: 5.250