{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:27:17Z","timestamp":1785529637917,"version":"3.56.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R21 MH131873, F31 MH130077"],"award-info":[{"award-number":["R21 MH131873, F31 MH130077"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R03 HD095056"],"award-info":[{"award-number":["R03 HD095056"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 (<jats:italic>never depressed<\/jats:italic>), 2) a history of MDD but no PND (<jats:italic>pre-pregnancy depression<\/jats:italic>), 3) a history of MDD and current PND (<jats:italic>recurrent depression<\/jats:italic>), and 4) no history of MDD but current PND (<jats:italic>perinatal-emergent depression<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpsyt.2025.1557560","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T05:27:13Z","timestamp":1746682033000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Levels of neuroactive steroids are elevated in those who develop first-onset depression early in pregnancy"],"prefix":"10.3389","volume":"16","author":[{"given":"Elizabeth S.","family":"Wenzel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan C.","family":"Barone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tory A.","family":"Eisenlohr-Moul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Alvernaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Pe\u00f1alver Bernab\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Spiro Santovito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim M. 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