Brain functional dynamics linked to major depression and anxiety: cross-sectional and longitudinal associations over 9 years.

Background. Resting-state fMRI (rs-fMRI) co-activation patterns (CAPs) capture recurrent whole-brain states that may index neurobiological substrates of affective psychopathology, yet whether their dynamics co-evolve with symptom severity over the long-term course of depression and anxiety remains unknown. Methods. We analyzed rs-fMRI and clinical data from 340 participants in the NESDA cohort (228 with a depressive and/or anxiety disorder, AFF) at baseline (Y0), 2-year (Y2), and 9-year (Y9) follow-up. Four CAPs were identified and validated. CAP dwell time and entries were related to depression (IDS), anxiety (BAI), and fear (FQ) severity between subjects and within individuals. Results. At baseline, attention-somatomotor (AT-SMCAP) dwell time was inversely associated with depression severity in CTR (rho = -0.29, q < 0.05) but not AFF (rho = 0.09, q = 0.79). Longitudinally, group-level trajectories showed no CAP-symptom coupling; it emerged only within individuals, where increases in frontoparietal-default-mode (FP-DMCAP) dwell time tracked worsening depression in AFF only (Y2 to Y9: rho = 0.47, q < 0.01). Conclusions. AT-SMCAP distinguished health from illness cross-sectionally, whereas FP-DMCAP indexed illness course within individuals, effects not captured by group-averaged analyses. These findings highlight individual-level CAP dynamics as relevant to longitudinal brain-symptom coupling, with implications for precision psychiatry.