2026 ECNP Congress

PS01-1091

White matter microstructure in the postpartum period and perinatal depressive symptoms: a TBSS study

Rosa Decorato — Y. Harrington, E. Melloni, E. Agnoletto, M. Paolini, S. Poletti, F. Benedetti · Vita-Salute San Raffaele University, Division of Neuroscience, Milano, Italy

2026 ECNP Congress

Introduction

Peripartum Depression is considered one of the most frequent complications of pregnancy, with a global prevalence estimated at around 17%[1]. Perinatal period is characterized by deep neurophysiological modifications in the maternal brain, which have been primarily investigated in relation to grey matter alterations [2]. More recently, increasing attention has been directed toward white matter (WM), which supports structural connectivity and neural communication[3]. Converging evidence indicates substantial brain plasticity during this transitional phase [4]; however, the relationship between WM microstructure and depressive symptoms across pregnancy and the postpartum period remains poorly understood. This prospective study aimed to investigate the associations between depressive symptoms measured during the third trimester of pregnancy and 6 weeks postpartum and white matter integrity measured in the postpartum period.

Methods

Fifty-nine women were recruited and assessed during pregnancy and the postpartum period. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) in the third trimester and 6 weeks postpartum. Based on established EPDS cut-off scores (>11 vs ≤11), participants were divided into groups. Diffusion tensor imaging (DTI) data were acquired during the postpartum period and analyzed using Tract-Based Spatial Statistics (TBSS). Group differences in white matter microstructure were examined using fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD), comparing EPDS-defined groups with independent samples t-tests. Age, center, and days from delivery to MRI scan were entered into the analyses as covariates.

Results

When groups were defined based on depressive symptoms in the third trimester, no significant differences were found in postpartum white matter diffusion indices. In contrast, postpartum EPDS-based group comparisons revealed significant microstructural differences. Women with EPDS scores >11 showed higher fractional anisotropy (FA) (p = 0.048) and lower radial diffusivity (RD) (p = 0.0046) compared to controls. These alterations were localized in white matter tracts including the right anterior corona radiata and the internal capsule.

Conclusions

These findings indicate that white matter microstructure in the postpartum period is associated with depressive symptoms assessed at the same time point, but not with those reported during the third trimester of pregnancy. Specifically, increased FA and reduced RD observed in women with clinically significant postpartum depressive symptoms may reflect compensatory mechanisms or microstructural alterations related to neurobiological processes specific to the postnatal period, such as stress-system activation, neuroinflammation, and hormonal fluctuations [5]. The absence of differences when groups are defined based on third-trimester symptoms suggests that postpartum white matter microstructure is not associated with earlier depressive symptoms, but rather with current symptomatology. However, given the cross-sectional nature of the imaging data, no inferences can be made about longitudinal changes or causal relationships. Overall, these findings highlight the postpartum period as a relevant window for identifying neurobiological correlates of perinatal depression and underscore the importance of distinguishing between prenatal and postnatal symptoms in their relationship with brain structure.

References

  1. Wang Z, Liu J, Shuai H, Cai Z, Fu X, Liu Y, Xiao X, Zhang W, Krabbendam E, Liu S, Liu Z, Li Z, Yang BX. Mapping global prevalence of depression among postpartum women. Transl Psychiatry. 2021 Oct 20;11(1):543. doi: 10.1038/s41398-021-01663-6. Erratum in: Transl Psychiatry. 2021 Dec 20;11(1):640. doi: 10.1038/s41398-021-01692-1. PMID: 34671011; PMCID: PMC8528847.
  2. Hoekzema E, Barba-Müller E, Pozzobon C, Picado M, Lucco F, García-García D, Soliva JC, Tobeña A, Desco M, Crone EA, Ballesteros A, Carmona S, Vilarroya O. Pregnancy leads to long-lasting changes in human brain structure. Nat Neurosci. 2017 Feb;20(2):287-296. doi: 10.1038/nn.4458. Epub 2016 Dec 19. PMID: 27991897.
  3. Barha CK, Nagamatsu LS, Liu-Ambrose T. Basics of neuroanatomy and neurophysiology. Handb Clin Neurol. 2016;138:53-68. doi: 10.1016/B978-0-12-802973-2.00004-5. PMID: 27637952.
  4. Kim P. Human Maternal Brain Plasticity: Adaptation to Parenting. New Dir Child Adolesc Dev. 2016 Sep;2016(153):47-58. doi: 10.1002/cad.20168. PMID: 27589497; PMCID: PMC5667351.
  5. Fransson E. Psychoneuroimmunology in the context of perinatal depression - Tools for improved clinical practice. Brain Behav Immun Health. 2021 Aug 25;17:100332. doi: 10.1016/j.bbih.2021.100332. PMID: 34589817; PMCID: PMC8474604.