2026 ECNP Congress

PS01-1093

Longitudinal endocrinological correlates of white matter integrity loss during the postpartum period

Hannah Klute — S. Meinert, S. Nehls, H. Schuch, M. Auchter, K. Maike, N. Chechko · University of Münster, Institute of Translational Psychiatry, Münster, Germany

2026 ECNP Congress

Introduction

The postpartum phase (including the following subphases [1]) constitutes a sensitive neurobiological window, associated with biological alterations and heightened vulnerability to depressive symptoms. While the acute postpartum phase (6-12 hours up until the first 10 days after birth) is characterized by the sudden withdrawal of previously stored hormones (e.g., progesterone, oestradiol), often accompanied by depressive symptoms termed ‘baby blues’ [2], hemodynamic recovery processes related to the urogenital system, metabolism and emotional status take [1] place during the subacute postpartum phase (lasts 2-6 weeks) while oestradiol levels gradually return to normal and progesterone levels rise slowly until, finally, ovarian function and therefore progesterone levels recover [3], muscle tone, connective tissue and the female overall physiology return to pre-pregnancy levels [1] during the delayed postpartum period (lasts up to 6 months). Despite substantial impairments on maternal well-being and child development, the underlying biological mechanisms of postpartal depression remain insufficiently understood. Hence, this study investigates longitudinal white matter remodelling in relation to endocrine withdrawal and the emergence of postpartum depressive symptoms, aiming to identify early neurobiological markers of risk, based on the hypothesis that during the first six weeks postpartum, alterations in white matter would be greatest in depression-related tracts and associated with shifts in oestradiol and progesterone.

Methods

Longitudinal diffusion tensor imaging (DTI) data were collected from N=25 healthy postpartum mothers with five follow-up measurements (starting at <10 days postpartum with repeated measures every 3 weeks up until week 12 postpartum and again at 24 weeks postpartum) and analysed using tract-based spatial statistics (TBSS). The effect of time on fractional anisotropy (FA) was estimated with linear mixed-effect models with random intercepts. To correct for multiple comparisons, threshold free cluster enhancement (TFCE) was used to correct α-values at the family-wise error rate (FWE; ptfce-FWE). In addition, oestradiol and progesterone levels were acquired.

Results

A significant decline in FA over time was found (ptfce-FWE<.001, ktotal=11.433 in 59 cluster, largest cluster: k=4.926, x=-36, y=-29, z=0) in the postpartum period in the corpus callosum, corona radiata, and superior longitudinal fasciculus. Post-hoc t-contrasts showed that this effect was driven by a sharp drop in FA values between the first and second measurement (>10 days to 3-4 weeks, ptfce-FWE=.003) with the onset of the subacute postpartum phase and again between the second and third measurement (3-4 to 6-7 weeks, ptfce-FWE=.004) up until the start of the delayed postpartum phase. The initial drop in FA values was associated with the decrease in oestradiol (ptfce-FWE=.048) and progesterone (ptfce-FWE=.003) levels that occurs after delivery, from the heightened values during pregnancy.

Conclusions

These findings successfully corroborate that the subacute postpartum phase (3-6 weeks post-delivery) constitutes a crucial transitional period marked by significant hormonal fluctuations that align with neurobiological changes. The sensitivity to these hormonal shifts, rather than absolute hormone levels, is considered pivotal in the development of postpartum depression. Given that the neurobiological alterations in the corpus callosum, corona radiata, and superior longitudinal fasciculus mirror those associated with Major Depressive Disorders, further investigation warrant to enhance our understanding of mood disorders.

References

  1. Romano, M., Cacciatore, A., Giordano, R., La Rosa, B., 2010. Postpartum period: Three distinct but continuous phases. Journal of Prenatal Medicine 4 (2), 22–25.
  2. Kennerley, H., Gath, D., 1989. Maternity blues. I. Detection and measurement by questionnaire. The British Journal of Psychiatry 155 (3), 356–362.
  3. Campbell, O. M. R., Gray, R. H., 1993. Characteristics and determinants of postpartum ovarian function in women in the United States. American Journal of Obstetrics and Gynecology 169 (1), 55–60.