D Porta-Casteràs1, M A Fullana2, D Tinoco3, I Martínez-Zalacaín4, J Pujol5, D J Palao1, C Soriano-Mas6, B J Harrison7, E Via8, N Cardoner1. 1. Mental Health Department, Unitat de Neurociència Traslacional. Parc Taulí University Hospital, Institut d'Investigació i Innovació Sanitària Parc Taulí (I3PT), Universitat Autònoma de Barcelona, CIBERSAM, Carlos III Health Institute, Bellaterra, Spain; Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain. 2. Institute of Neurosciences, Hospital Clinic, CIBERSAM, Barcelona, Spain. 3. Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain. 4. Department of Psychiatry, Bellvitge University Hospital -IDIBELL, CIBERSAM, Carlos III Health Institute, Barcelona, Spain; Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain. 5. MRI Research Unit,Hospital del Mar, CIBERSAM G21, Barcelona,Spain. 6. Department of Psychiatry, Bellvitge University Hospital -IDIBELL, CIBERSAM, Carlos III Health Institute, Barcelona, Spain; Department of Psychobiology and Methodology of Health Sciences. Universitat Autònoma de Barcelona, Barcelona, Spain. 7. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Victoria, Australia. 8. Mental Health Department, Unitat de Neurociència Traslacional. Parc Taulí University Hospital, Institut d'Investigació i Innovació Sanitària Parc Taulí (I3PT), Universitat Autònoma de Barcelona, CIBERSAM, Carlos III Health Institute, Bellaterra, Spain; Child and Adolescent Psychiatry and Psychology Department, Hospital Sant Joan de Déu of Barcelona, Barcelona, Spain; Child and Adolescent Mental Health Research Group, Institut de Recerca Sant Joan de Déu, Barcelona, Spain. Electronic address: evia@sjdhospitalbarcelona.org.
Abstract
BACKGROUND: Current brain-based theoretical models of generalized anxiety disorder (GAD) suggest a dysfunction of amygdala-ventromedial prefrontal cortex emotional regulatory mechanisms. These alterations might be reflected by an altered resting state functional connectivity between both areas and could extend to vulnerable non-clinical samples such as high worriers without a GAD diagnosis. However, there is a lack of information in this regard. METHODS: We investigated differences in resting state functional connectivity between the basolateral amygdala and the ventromedial prefrontal cortex (amygdala-vmPFC) in 28 unmedicated participants with GAD, 28 high-worriers and 28 low-worriers. We additionally explored selected clinical variables as predictors of amygdala-vmPFC connectivity, including anxiety sensitivity. RESULTS: GAD participants presented higher left amygdala-vmPFC connectivity compared to both groups of non-GAD participants, and there were no differences between the latter two groups. In our exploratory analyses, concerns about the cognitive consequences of anxiety (the cognitive dimension of anxiety sensitivity) were found to be a significant predictor of the left amygdala-vmPFC connectivity. LIMITATIONS: The cross-sectional nature of our study preclude us from assessing if functional connectivity measures and anxiety sensitivity scores entail an increased risk of GAD. CONCLUSIONS: These results suggest a neurobiological qualitative distinction at the level of the amygdala-vmPFC emotional-regulatory system in GAD compared to non-GAD participants, either high- or low-worriers. At this neural level, they question previous hypotheses of continuity between high worries and GAD development. Instead, other anxiety traits such as anxiety sensitivity might confer a greater proneness to the amygdala-vmPFC connectivity alterations observed in GAD.
BACKGROUND: Current brain-based theoretical models of generalized anxiety disorder (GAD) suggest a dysfunction of amygdala-ventromedial prefrontal cortex emotional regulatory mechanisms. These alterations might be reflected by an altered resting state functional connectivity between both areas and could extend to vulnerable non-clinical samples such as high worriers without a GAD diagnosis. However, there is a lack of information in this regard. METHODS: We investigated differences in resting state functional connectivity between the basolateral amygdala and the ventromedial prefrontal cortex (amygdala-vmPFC) in 28 unmedicated participants with GAD, 28 high-worriers and 28 low-worriers. We additionally explored selected clinical variables as predictors of amygdala-vmPFC connectivity, including anxiety sensitivity. RESULTS:GADparticipants presented higher left amygdala-vmPFC connectivity compared to both groups of non-GADparticipants, and there were no differences between the latter two groups. In our exploratory analyses, concerns about the cognitive consequences of anxiety (the cognitive dimension of anxiety sensitivity) were found to be a significant predictor of the left amygdala-vmPFC connectivity. LIMITATIONS: The cross-sectional nature of our study preclude us from assessing if functional connectivity measures and anxiety sensitivity scores entail an increased risk of GAD. CONCLUSIONS: These results suggest a neurobiological qualitative distinction at the level of the amygdala-vmPFC emotional-regulatory system in GAD compared to non-GADparticipants, either high- or low-worriers. At this neural level, they question previous hypotheses of continuity between high worries and GAD development. Instead, other anxiety traits such as anxiety sensitivity might confer a greater proneness to the amygdala-vmPFC connectivity alterations observed in GAD.
Authors: Ian H Kratter; Ahmed Jorge; Michael T Feyder; Ashley C Whiteman; Yue-Fang Chang; Luke C Henry; Jordan F Karp; R Mark Richardson Journal: Transl Psychiatry Date: 2022-05-27 Impact factor: 7.989
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Authors: Anderson M Winkler; Daniel S Pine; Anita Harrewijn; Elise M Cardinale; Nynke A Groenewold; Janna Marie Bas-Hoogendam; Moji Aghajani; Kevin Hilbert; Narcis Cardoner; Daniel Porta-Casteràs; Savannah Gosnell; Ramiro Salas; Andrea P Jackowski; Pedro M Pan; Giovanni A Salum; Karina S Blair; James R Blair; Mira Z Hammoud; Mohammed R Milad; Katie L Burkhouse; K Luan Phan; Heidi K Schroeder; Jeffrey R Strawn; Katja Beesdo-Baum; Neda Jahanshad; Sophia I Thomopoulos; Randy Buckner; Jared A Nielsen; Jordan W Smoller; Jair C Soares; Benson Mwangi; Mon-Ju Wu; Giovana B Zunta-Soares; Michal Assaf; Gretchen J Diefenbach; Paolo Brambilla; Eleonora Maggioni; David Hofmann; Thomas Straube; Carmen Andreescu; Rachel Berta; Erica Tamburo; Rebecca B Price; Gisele G Manfro; Federica Agosta; Elisa Canu; Camilla Cividini; Massimo Filippi; Milutin Kostić; Ana Munjiza Jovanovic; Bianca A V Alberton; Brenda Benson; Gabrielle F Freitag; Courtney A Filippi; Andrea L Gold; Ellen Leibenluft; Grace V Ringlein; Kathryn E Werwath; Hannah Zwiebel; André Zugman; Hans J Grabe; Sandra Van der Auwera; Katharina Wittfeld; Henry Völzke; Robin Bülow; Nicholas L Balderston; Monique Ernst; Christian Grillon; Lilianne R Mujica-Parodi; Helena van Nieuwenhuizen; Hugo D Critchley; Elena Makovac; Matteo Mancini; Frances Meeten; Cristina Ottaviani; Tali M Ball; Gregory A Fonzo; Martin P Paulus; Murray B Stein; Raquel E Gur; Ruben C Gur; Antonia N Kaczkurkin; Bart Larsen; Theodore D Satterthwaite; Jennifer Harper; Michael Myers; Michael T Perino; Chad M Sylvester; Qiongru Yu; Ulrike Lueken; Dick J Veltman; Paul M Thompson; Dan J Stein; Nic J A Van der Wee Journal: Transl Psychiatry Date: 2021-10-01 Impact factor: 7.989