Brain activation and connectivity after 2-3 weeks of escitalopram administration in anxiety disorders: A randomised trial.
| Title: | Brain activation and connectivity after 2-3 weeks of escitalopram administration in anxiety disorders: A randomised trial. |
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| Authors: | Lukow PB; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK. Electronic address: p.lukow@ucl.ac.uk.; Lowther M; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK; Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, 15 Chaucer Road, CB2 7EF, UK.; Pike AC; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK; Department of Psychology, Institute of Mental Health Research York & York Biomedical Research Institute, University of York, York, YO10 5DD, UK.; Yamamori Y; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK.; Chavanne AV; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK; Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale, INSERM U1299 'Trajectoires développementales Psychiatrie', Ecole Normale Supérieure Paris-Saclay, CNRS UMR 9010, Centre Borelli, Gif-sur-Yvette, France; Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.; Gormley S; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK.; Aylward J; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK.; Vera CE; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, Mail Code 0433, La Jolla, CA, 92093-0433, United States of America.; McCloud T; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK; UCL Division of Psychiatry, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK.; Goble T; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK.; Rodriguez-Sanchez J; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK; Centre for Medical Image Computing, Department of Computer Science, University College London, London, WC1V 6LJ, UK.; Tuominen EW; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK.; Buehler SK; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK.; Kirk P; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK; Emotion and Development Branch, National Institute of Mental Health, Bldg. 15K, MSC 2670, Bethesda, MD, 20892-2670, United States of America.; Robinson OJ; Institute of Cognitive Neuroscience, Alexandra House, 17-19 Queen Square, WC1N 3AZ, London, UK. |
| Source: | Journal of affective disorders [J Affect Disord] 2026 Feb 01; Vol. 394 (Pt B), pp. 120682. Date of Electronic Publication: 2025 Nov 13. |
| Publication Type: | Journal Article; Randomized Controlled Trial |
| Language: | English |
| Journal Info: | Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7906073 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2517 (Electronic) Linking ISSN: 01650327 NLM ISO Abbreviation: J Affect Disord Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press. |
| MeSH Terms: | Anxiety Disorders*/drug therapy ; Anxiety Disorders*/physiopathology ; Selective Serotonin Reuptake Inhibitors*/administration & dosage ; Selective Serotonin Reuptake Inhibitors*/pharmacology ; Selective Serotonin Reuptake Inhibitors*/therapeutic use ; Escitalopram*/administration & dosage ; Escitalopram*/therapeutic use ; Escitalopram*/pharmacology ; Amygdala*/drug effects ; Amygdala*/physiopathology ; Cerebral Cortex*/drug effects ; Cerebral Cortex*/physiopathology ; Citalopram*/pharmacology; Emotions/drug effects ; Neural Pathways/drug effects ; Neural Pathways/physiopathology ; Humans ; Female ; Double-Blind Method ; Adult ; Magnetic Resonance Imaging ; Male ; Young Adult |
| Abstract: | Despite the extensive use of selective serotonin reuptake inhibitors (SSRIs) for anxiety treatment worldwide, their neural mechanism of action remains poorly understood. Based on a systematic line of experimental medicine studies from our laboratory, we posited that SSRI-mediated anxiolysis may be driven by a sustained reduction in positive coupling between the dorsomedial cortex and amygdala in anxious individuals. We conducted a randomised, double-blind, placebo-controlled study investigating amygdala-dorsomedial cortex activation and connectivity during emotion processing after 2-3-week SSRI administration in anxious individuals (ANX) compared to healthy controls (HC). The baseline analysis included 96 HC and 45 ANX participants. The follow-up analysis included 86 HC (placebo n = 40, 73 % female, SSRI n = 46, 74 % female) and 42 ANX participants (placebo n = 22, 86 % female, SSRI n = 20, 80 % female). Consistent with predictions, 2-3 weeks of escitalopram administration altered bilateral amygdala connectivity with the dorsomedial cortex during emotional face processing in people with anxiety disorders compared to healthy controls. However, the effect was in the opposite direction to predicted - positive coupling increased following SSRI in the patient group (right amygdala: ANX-SSRI vs HC-SSRI t = 2.4, p = 0.02; left amygdala: ANX-SSRI vs HC-SSRI t = 2.6, p = 0.01). A follow-up sensitivity analysis confirmed this to be a bilateral effect. These findings suggest that our simple hypothesis of SSRIs inducing a reduction in amygdala-dorsomedial cortex connectivity is incorrect, and the associated brain connectivity may instead increase in the initial weeks of drug administration. The study is registered as a clinical trial at https://www.clinicaltrials.gov. Its clinical trial name is: 'The Effect of SSRIs on Threat of Shock Potentiated Neural Circuitry', number: NCT07074652, URL: https://www.clinicaltrials.gov/study/NCT07074652.; (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Oliver J Robinson reports financial support was provided by Medical Research Council. Oliver J Robinson reports equipment, drugs, or supplies were provided by Lundbeck LLC. Oliver J Robinson reports a relationship with Medical Research Council and Roche that includes: funding grants. Alexandra C Pike reports a relationship with Medical Research Council and Roche that includes: travel reimbursement. Oliver J Robinson reports a relationship with PEAK that includes: consulting or advisory. Oliver J Robinson reports a relationship with IESO Digital Health that includes: consulting or advisory. Oliver J Robinson reports a relationship with Roche that includes: consulting or advisory. Oliver J Robinson reports a relationship with Blackthorn Therapeutics Inc. that includes: consulting or advisory. Alexandra C Pike reports a relationship with Wellcome Trust that includes: funding grants. Alexandra C Pike reports a relationship with Academy of Medical Sciences that includes: funding grants. Tayla McCloud reports a relationship with Wellcome Trust that includes: employment. OJR sat on the committee of the British Association for Psychopharmacology until 2022. ACP sits on the Council for the British Association for Psychopharmacology. The other authors declare no competing interests. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Activation; Anxiety; Connectivity; Emotion; Escitalopram; Selective serotonin reuptake inhibitor |
| Molecular Sequence: | ClinicalTrials.gov NCT07074652 |
| Substance Nomenclature: | 0 (Selective Serotonin Reuptake Inhibitors); 4O4S742ANY (Escitalopram); 0DHU5B8D6V (Citalopram) |
| Entry Date(s): | Date Created: 20251115 Date Completed: 20251129 Latest Revision: 20251217 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.jad.2025.120682 |
| PMID: | 41241072 |
| Database: | MEDLINE |
Journal Article; Randomized Controlled Trial