Running therapy reorganizes dynamic brain networks linked to symptom improvement in affective disorders

Julian Gaviria Lopez; Guido Van Wingen; Chris Vriend; Laura K M Han; Jennifer Labus; Gitte M Knudsen; Brenda W J H Penninx

doi:10.1016/j.bpsc.2026.05.011

Running therapy reorganizes dynamic brain networks linked to symptom improvement in affective disorders

Biol Psychiatry Cogn Neurosci Neuroimaging. 2026 Jun 4:S2451-9022(26)00156-4. doi: 10.1016/j.bpsc.2026.05.011. Online ahead of print.

Authors

Julian Gaviria Lopez¹, Guido Van Wingen², Chris Vriend³, Laura K M Han², Jennifer Labus⁴, Gitte M Knudsen⁵, Brenda W J H Penninx²

Affiliations

¹ Psychiatry department, Amsterdam UMC Location Vrije Universiteit, Amsterdam, the Netherlands. Electronic address: jualgalo@gmail.com.
² Psychiatry department, Amsterdam UMC Location Vrije Universiteit, Amsterdam, the Netherlands; Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, the Netherlands.
³ Psychiatry department, Amsterdam UMC Location Vrije Universiteit, Amsterdam, the Netherlands; Department of Anatomy & Neurosciences, Amsterdam UMC, Location Vrije Universiteit Amsterdam,; Amsterdam Neuroscience, Brain Imaging, Amsterdam, the Netherlands. Anatomy and Neurosciences, De Boelelaan 1117, Amsterdam, The Netherlands.
⁴ G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche & Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California.
⁵ Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. e; Department of Clinical Medicine, Faculty of Health and Medicine Sciences, University of Copenhagen, Copenhagen, Denmark.

PMID: 42248331
DOI: 10.1016/j.bpsc.2026.05.011

Abstract

Background: Exercise therapy reduces depressive and anxiety symptoms, but its neural mechanisms remain unclear. We examined whether running therapy reorganizes dynamic brain functional connectivity in affective disorders.

Methods: Resting-state fMRI was analyzed at baseline in 66 healthy controls and 50 individuals with affective disorders. Co-activation pattern (CAP) analysis identified recurring whole-brain states and their temporal dynamics. After baseline comparisons, patients received 16 weeks of running therapy or antidepressant treatment. We then examined treatment-related CAP changes and their associations with symptom improvement.

Results: At baseline, individuals with affective disorders showed fewer occurrences and shorter dwell time of the visual-somatosensory-subcortical CAP (VS-SC_CAP) than controls (both p ≤ 0.04, η²p ≈ 0.04 to 0.05). Running therapy induced a treatment-specific reorganization of brain dynamics, with decreased default mode CAP (DM_CAP) occurrences (F = 8.18, p = 0.01, η²p = 0.13) and dwell time (F = 11.51, p < 0.001, η²p= 0.19), and increased VS-SC_CAP occurrences (F = 8.10, p = 0.01, η²p = 0.13) and entries (F = 5.39, p = 0.03, η²p = 0.08). Greater reductions in DM_CAP entries and transitions from DM_CAP to VS-SC_CAP were associated with greater improvement in anxiety- and fear-related symptoms (rho = -0.54 to -0.45, all p_FDR ≤ 0.03).

Conclusions: Running therapy was associated with treatment-specific reorganization of large-scale brain dynamics in affective disorders. Symptom improvement was linked to changes in default mode CAP dynamics and transitions between default mode and visual-somatosensory states.

Keywords: Brain networks; Running therapy; affective disorders; depression, anxiety; dynamic functional connectivity (dFC).