Brain functional dynamics linked to major depression and anxiety: cross-sectional and longitudinal associations over 9 years.
- 1Amsterdam UMC
Abstract
BackgroundResting-state fMRI (rs-fMRI) co-activation patterns (CAPs) capture recurrent whole-brain states that may index neurobiological substrates of affective psychopathology, but whether their temporal dynamics co-evolve with symptom severity over the naturalistic long-term course of depression and anxiety remains unknown.
MethodsWe examined rs-fMRI and clinical data from 340 participants of the NESDA neuroimaging cohort [228 with major depression (MDD) and/or an anxiety disorder (AFF), 112 controls (CTR)] collected at baseline (Y0), 2-year (Y2), and 9-year (Y9) follow-up. Four CAPs were identified, internally validated, externally replicated against an independent dataset, and quantified by dwell time (time spent of each brain CAP) and entries (initiation of each CAP). These metrics were related to depression symptomatology (IDS score), anxiety (BAI), and fear (FQ) severity at two levels: cross-sectionally, between subjects and groups, and longitudinally, through within-person associations between changes in CAP expression and changes in symptoms severity.
ResultsAt baseline, attention-somatomotor (AT-SMCAP) dwell time was negatively associated with depression severity in controls (rho = -0.29, q < 0.05), an association absent in individuals with AFF ( rho = 0.09, q = 0.79;). Longitudinally, group-level CAP trajectories did not differ between AFF and CTR, but within-person changes in frontoparietal-default-mode (FP-DMCAP) dwell time tracked changes in depression severity exclusively in AFF (Y2[->]Y9: rho = 0.47, q = 0.04). Patients whose FP-DMCAP dwell time increased were those whose depression failed to improve.
ConclusionsCAP dwell time carried clinical meaning at two levels: AT-SMCAP distinguished health from illness at baseline, while FP-DMCAP dwell time indexed within-person illness course over nine years. Because FP-DMCAP co-activates frontoparietal control with default-mode regions implicated in rumination, its rebound in dwell time may reflect a shift toward perseverative self-referential processing in patients who fail to remit. These findings position CAP dwell-time-symptom coupling as a neurobiologically grounded, individually resolved marker of naturalistic illness course relevant to precision psychiatry.
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BibTeX
@misc{gaviria2026brain,
title = {{Brain functional dynamics linked to major depression and anxiety: cross-sectional and longitudinal associations over 9 years.}},
author = {J. Gaviria and G. van Wingen and R. Jansen and J. S. Labus and B. Penninx},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.08.26362586},
url = {https://www.medrxiv.org/content/10.64898/2026.09.08.26362586v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Brain functional dynamics linked to major depression and anxiety: cross-sectional and longitudinal associations over 9 years.
AU - J. Gaviria
AU - G. van Wingen
AU - R. Jansen
AU - J. S. Labus
AU - B. Penninx
PY - 2026
DA - 2026/09/08
PB - medRxiv
DO - 10.64898/2026.09.08.26362586
UR - https://www.medrxiv.org/content/10.64898/2026.09.08.26362586v1
AB - BackgroundResting-state fMRI (rs-fMRI) co-activation patterns (CAPs) capture recurrent whole-brain states that may index neurobiological substrates of affective psychopathology, but whether their temporal dynamics co-evolve with symptom severity over the naturalistic long-term course of depression and anxiety remains unknown. MethodsWe examined rs-fMRI and clinical data from 340 participants of the NESDA neuroimaging cohort [228 with major depression (MDD) and/or an anxiety disorder (AFF), 112 controls (CTR)] collected at baseline (Y0), 2-year (Y2), and 9-year (Y9) follow-up. Four CAPs were identified, internally validated, externally replicated against an independent dataset, and quantified by dwell time (time spent of each brain CAP) and entries (initiation of each CAP). These metrics were related to depression symptomatology (IDS score), anxiety (BAI), and fear (FQ) severity at two levels: cross-sectionally, between subjects and groups, and longitudinally, through within-person associations between changes in CAP expression and changes in symptoms severity. ResultsAt baseline, attention-somatomotor (AT-SMCAP) dwell time was negatively associated with depression severity in controls (rho = -0.29, q < 0.05), an association absent in individuals with AFF ( rho = 0.09, q = 0.79;). Longitudinally, group-level CAP trajectories did not differ between AFF and CTR, but within-person changes in frontoparietal-default-mode (FP-DMCAP) dwell time tracked changes in depression severity exclusively in AFF (Y2[->]Y9: rho = 0.47, q = 0.04). Patients whose FP-DMCAP dwell time increased were those whose depression failed to improve. ConclusionsCAP dwell time carried clinical meaning at two levels: AT-SMCAP distinguished health from illness at baseline, while FP-DMCAP dwell time indexed within-person illness course over nine years. Because FP-DMCAP co-activates frontoparietal control with default-mode regions implicated in rumination, its rebound in dwell time may reflect a shift toward perseverative self-referential processing in patients who fail to remit. These findings position CAP dwell-time-symptom coupling as a neurobiologically grounded, individually resolved marker of naturalistic illness course relevant to precision psychiatry.
ER -