Levels of Neuroactive Steroids are Elevated in those who Develop First-Onset Depression Early in Pregnancy

Elizabeth S Wenzel^1,2*Jordan C Barone³Tory Anne Eisenlohr-Moul³Suzanne Alvernaz⁴Beatriz Peñalver Bernabé⁴Luca Spiro Santovito³Ibrahim M M Gdyana³Graziano Pinna³Pauline M. Maki³

• ¹Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, United States
• ²Psychology, University of Illinois Chicago, Chicago, Illinois, United States
• ³Psychiatry, University of Illinois Chicago, Chicago, Illinois, United States
• ⁴Biomedical Engineering, University of Illinois Chicago, Chicago, Illinois, United States

Background: Allopregnanolone (ALLO) plays a key role in the pathogenesis of postpartum depression. However, ALLO levels have been variably associated with depression during pregnancy. It is unknown if a pre-pregnancy history of major depressive disorder (MDD), which is associated with blunted neurosteroidogenesis, and timing of perinatal depression (PND) may influence the association between neuroactive steroids (NAS) and PND.Objective: To investigate differences in ALLO and other NAS levels during the first (T1) and second (T2) trimesters based on pre-pregnancy history of MDD and current PND.Methods: Participants completed a diagnostic test of depression, blood samples and mental health history. Ninety-eight participants contributed data in T1 and 93 in T2. Levels of ALLO, pregnanolone (PA), isoallopregnanolone (ISO), epipregnanolone (EPI), and progesterone (P4) were quantified using gas chromatography-mass spectrometry. Analyses of covariance with pairwise comparisons predicted NAS levels from categorized groups of those with: 1) no history of MDD and no PND (never depressed), 2) a history of MDD but no PND (pre-pregnancy depression), 3) a history of MDD and current PND (recurrent depression), and 4) no history of MDD but current PND (perinatal-emergent depression).Results: Across groups, there were marginally significant differences in T1 ALLO (p=.05) and ISO levels (p=.05). T1 ALLO levels were higher in the perinatal-emergent versus never depressed (p=.007) and recurrent depression (p=.05) groups. ISO levels were higher in the perinatal-emergent versus recurrent depression (p=.02) and never depressed (p=.03) groups. In T2, there were significant differences in PA levels (p=.04) and marginally significant differences in ALLO (p=.07) and ISO levels (p=.09). ALLO levels were higher in the perinatal-emergent versus recurrent depression group (p=.05), and in the never depressed (p=.05) and pre-pregnancy depression groups (p=.04) compared to recurrent depression. PA levels were higher in the perinatal-emergent depression versus never depressed (p=.02) and recurrent depression (p=.01) groups, and ISO levels were higher in the perinatal-emergent depression versus never depressed (p=.03) and recurrent depression (p=.07) groups.Conclusions: These results suggest differing NAS-related mechanisms of pathogenesis across clinical phenotypes based on pre-pregnancy history of MDD and timing of PND onset. Future research should account for these factors when investigating NAS and PND.