Bidirectional associations between perinatal allopregnanolone and depression severity with postpartum gray matter volume in adult women.

Background: Perinatal depression (PND) is a debilitating condition affecting maternal well-being and child development. Allopregnanolone (ALLO) is important to perinatal neuroplasticity, however its relationship with depression severity and postpartum structural brain volume is unknown.

Method: We examined perinatal temporal dynamics and bidirectional associations between ALLO and depression severity and the association between these variables and postpartum gray matter volume, using a random intercept cross-lagged panel model.

Results: We identified a unidirectional predictive relationship between PND severity and ALLO concentration, suggesting greater depression severity early in the perinatal period may contribute to subsequent changes in ALLO concentration (β = 0.26, p = 0.009), while variations in ALLO levels during the perinatal period influences the development and severity of depressive symptoms later in the postpartum period (β = 0.38, p = 0.007). Antepartum depression severity (Visit 2, β = 0.35, p = 0.004), ALLO concentration (Visit 2, β = 0.37, p = 0.001), and postpartum depression severity (Visit 3, β = 0.39, p = 0.031), each predicted the right anterior cingulate volume. Antepartum ALLO concentration (Visit 2, β = 0.29, p = 0.001) predicted left suborbital sulcus volume. Antepartum depression severity (Visit 1, β = 0.39, p = 0.006 and Visit 2, β = 0.48, p < 0.001) predicted the right straight gyrus volume. Postpartum depression severity (Visit 3, β = 0.36, p = 0.001) predicted left middle-posterior cingulate volume.

Conclusion: These results provide the first evidence of bidirectional associations between perinatal ALLO and depression severity with postpartum gray matter volume.