Longitudinal structural connectome changes linked to recovery and persistence in women with postpartum depression

Clinical outcomes in postpartum depression (PPD) are highly heterogeneous, yet the neurobiological mechanisms underlying recovery remain unclear. Identifying network-based biomarkers that reflect the brain's capacity for adaptive reorganization may improve prognostic accuracy and support individualized treatment.

We conducted a longitudinal diffusion tensor imaging (DTI) study of 115 PPD patients and 40 healthy postpartum controls. All participants underwent DTI scans and clinical assessments at baseline (Time 1), 3 months (Time 2), and 6 months (Time 3). Based on 6-month outcomes, patients were classified into a recovery group (PPD-R, N = 72) and a non-recovery group (PPD-NR, N = 43). Graph-theoretical analyses assessed network topology across timepoints, focusing on rich-club connections, feeder connections, and local connections, as well as small-world properties. Psychosocial variables including perceived social support were also evaluated.

At baseline, both PPD-R and PPD-NR groups showed reduced local connections (F = 13.034, P < 0.001) and small-world properties (F = 17.219, P < 0.001). During follow-up, only the PPD-R group exhibited significant recovery of rich-club connections (t_time1-time2 = -3.900, P < 0.001; t_time1-time3 = -4.325, P < 0.001), which correlated with initial small-world properties (β_{rich-club connections} = 0.456, P < 0.001; β_{∆rich-club connections} = 0.405, P < 0.001) and predicted final depression severity (OR = 0.713 [95%CI: 0.568-0.832], AUC = 0.819, P < 0.001). Perceived social support significantly moderated the relationship between small-world properties and rich-club recovery (β_{perceived social support-small-world properties} = 0.223, P = 0.002).

Recovery from PPD was associated with selective reorganization of rich-club connections. Efficient small-world topology was related to greater rich-club reorganization, and perceived social support moderated this relationship. These findings suggest that rich-club connections may serve as a potential prognostic marker of recovery in PPD.