Resting-state functional connectivity in anxiety disorders: a multicenter fMRI study

Till Langhammer; Kevin Hilbert; Dirk Adolph; Volker Arolt; Sophie Bischoff; Joscha Böhnlein; Jan C Cwik; Udo Dannlowski; Jürgen Deckert; Katharina Domschke; Ricarda Evens; Thomas Fydrich; Bettina Gathmann; Alfons O Hamm; Ingmar Heinig; Martin J Herrmann; Maike Hollandt; Markus Junghoefer; Tilo Kircher; Katja Koelkebeck; Elisabeth J Leehr; Martin Lotze; Jürgen Margraf; Jennifer L M Mumm; Andre Pittig; Jens Plag; Jan Richter; Kati Roesmann; Isabelle C Ridderbusch; Silvia Schneider; Hanna Schwarzmeier; Fabian Seeger; Niklas Siminski; Thomas Straube; Andreas Ströhle; Christoph Szeska; Hans-Ulrich Wittchen; Adrian Wroblewski; Yunbo Yang; Benjamin Straube; Ulrike Lueken

doi:10.1038/s41380-024-02768-2

Resting-state functional connectivity in anxiety disorders: a multicenter fMRI study

Mol Psychiatry. 2024 Oct 4. doi: 10.1038/s41380-024-02768-2. Online ahead of print.

Authors

Till Langhammer¹, Kevin Hilbert^{2

3}, Dirk Adolph⁴, Volker Arolt⁵, Sophie Bischoff⁶, Joscha Böhnlein⁵, Jan C Cwik^{7

8}, Udo Dannlowski⁵, Jürgen Deckert⁹, Katharina Domschke¹⁰, Ricarda Evens², Thomas Fydrich², Bettina Gathmann¹¹, Alfons O Hamm¹², Ingmar Heinig¹³, Martin J Herrmann⁹, Maike Hollandt^{12

14}, Markus Junghoefer^{15

16}, Tilo Kircher¹⁷, Katja Koelkebeck¹⁸, Elisabeth J Leehr⁵, Martin Lotze¹⁹, Jürgen Margraf⁵, Jennifer L M Mumm⁶, Andre Pittig²⁰, Jens Plag²¹, Jan Richter²², Kati Roesmann^{15

23}, Isabelle C Ridderbusch¹⁷, Silvia Schneider²⁴, Hanna Schwarzmeier¹¹, Fabian Seeger¹¹, Niklas Siminski²⁵, Thomas Straube^{11

16}, Andreas Ströhle⁶, Christoph Szeska^{12

26}, Hans-Ulrich Wittchen^{13

27}, Adrian Wroblewski¹⁷, Yunbo Yang^{17

22}, Benjamin Straube¹⁷, Ulrike Lueken^{2

28}

Affiliations

¹ Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany. till.langhammer@hu-berlin.de.
² Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
³ Department of Psychology, HMU Health and Medical University Erfurt, Erfurt, Germany.
⁴ Mental Health Research and Treatment Center, Faculty of Psychology, Ruhr-Universität Bochum, Bochum, Germany.
⁵ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
⁶ Department of Psychiatry and Psychotherapy, Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁷ Department of Clinical Psychology and Psychotherapy, University of Cologne, Cologne, Germany.
⁸ Department of Psychology and Psychotherapy, Witten/Herdecke University, Witten, Germany.
⁹ Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University of Würzburg, Würzburg, Germany.
¹⁰ Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
¹¹ Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany.
¹² Department of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany.
¹³ Institute for Clinical Psychology and Psychotherapy, Technical University of Dresden, Dresden, Germany.
¹⁴ Department of Clinical Psychology and Psychotherapy, University of Greifswald, Greifswald, Germany.
¹⁵ Institute for Biomagnetism and Biosignalanalysis, University of Münster, Münster, Germany.
¹⁶ Otto Creutzfeldt Center for Cognitive and Behavioral Neuroscience, University of Münster, Münster, Germany.
¹⁷ Department of Psychiatry and Psychotherapy and Center for Mind, Brain and Behavior - CMBB, Philipps-Universität Marburg, Marburg, Germany.
¹⁸ LVR-University Hospital Essen, Department of Psychiatry and Psychotherapy, University of Duisburg-Essen, Duisburg, Germany.
¹⁹ Functional Imaging Unit, Diagnostic Radiology, University Medicine Greifswald, Greifswald, Germany.
²⁰ Translational Psychotherapy, Institute of Psychology, University of Goettingen, Göttingen, Germany.
²¹ Department of Medicine, Institute for Mental Health and Behavioral Medicine, HMU Health and Medical University, Potsdam, Germany.
²² Department of Experimental Psychopathology, University of Hildesheim, Hildesheim, Germany.
²³ Institute for Psychology, Clinical Psychology and Psychotherapy in Childhood and Adolescence, University of Osnabrueck, Osnabruck, Germany.
²⁴ Department of Clinical Child and Adolescent Psychology, Ruhr-University Bochum, Bochum, Germany.
²⁵ Center for Mental Health, Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
²⁶ Department of Biological Psychology and Affective Science, University of Potsdam, Potsdam, Germany.
²⁷ Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University (LMU) Muenchen, Munich, Germany.
²⁸ German Center for Mental Health (DZPG), partner site Berlin/Potsdam, Berlin, Germany.

PMID: 39367057
DOI: 10.1038/s41380-024-02768-2

Abstract

Anxiety disorders (AD) are associated with altered connectivity in large-scale intrinsic brain networks. It remains uncertain how much these signatures overlap across different phenotypes due to a lack of well-powered cross-disorder comparisons. We used resting-state functional magnetic resonance imaging (rsfMRI) to investigate differences in functional connectivity (FC) in a cross-disorder sample of AD patients and healthy controls (HC). Before treatment, 439 patients from two German multicenter clinical trials at eight different sites fulfilling a primary diagnosis of panic disorder and/or agoraphobia (PD/AG, N = 154), social anxiety disorder (SAD, N = 95), or specific phobia (SP, N = 190) and 105 HC underwent an 8 min rsfMRI assessment. We performed categorical and dimensional regions of interest (ROI)-to-ROI analyses focusing on connectivity between regions of the defensive system and prefrontal regulation areas. AD patients showed increased connectivity between the insula and the thalamus compared to controls. This was mainly driven by PD/AG patients who showed increased (insula/hippocampus/amygdala-thalamus) and decreased (dorsomedial prefrontal cortex/periaqueductal gray-anterior cingulate cortex) positive connectivity between subcortical and cortical areas. In contrast, SAD patients showed decreased negative connectivity exclusively in cortical areas (insula-orbitofrontal cortex), whereas no differences were found in SP patients. State anxiety associated with the scanner environment did not explain the FC between these regions. Only PD/AG patients showed pronounced connectivity changes along a widespread subcortical-cortical network, including the midbrain. Dimensional analyses yielded no significant results. The results highlighting categorical differences between ADs at a systems neuroscience level are discussed within the context of personalized neuroscience-informed treatments. PROTECT-AD's registration at NIMH Protocol Registration System: 01EE1402A and German Register of Clinical Studies: DRKS00008743. SpiderVR's registration at ClinicalTrials.gov: NCT03208400.

Associated data

ClinicalTrials.gov/NCT03208400

Abstract

Associated data

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