Blood transcriptomic signatures associated with depression, or the risk for depression, in pregnant women from the Psychiatry Research And Motherhood - Depression (PRAM-D) study

TY - JOUR

T1 - Blood transcriptomic signatures associated with depression, or the risk for depression, in pregnant women from the Psychiatry Research And Motherhood - Depression (PRAM-D) study

AU - Di Benedetto, Maria Grazia

AU - Priestley, Kristi M.S.

AU - Cattane, Nadia

AU - Genini, Patrizia

AU - Saleri, Samantha

AU - Biaggi, Alessandra

AU - Bind, Rebecca H.

AU - Conroy, Susan

AU - Du Preez, Andrea

AU - Hazelgrove, Katie

AU - Osborne, Sarah

AU - Pawlby, Susan

AU - Sethna, Vaheshta

AU - Pariante, Carmine M.

AU - Cattaneo, Annamaria

N1 - Publisher Copyright: © The Author(s) 2025.

PY - 2025/12

Y1 - 2025/12

N2 - During pregnancy multiple biological systems undergo consistent modifications, in particular the hormonal axes and the immune system. Moreover, while it is well known that pregnant women suffering from depression show alterations in these systems, the exact underlying mechanisms are still not clear. For this reason, in this study, we explored the blood transcriptomic profile and related pathways in 41 pregnant women with a current diagnosis of depression, 23 pregnant women, who were not depressed in pregnancy but, because of a history of depressive episodes, were considered at high risk of developing antenatal depression (history-only), and 28 pregnant women who had never experienced depression in their life, including the current pregnancy. Based on resulting differentially expressed genes, we identified 28 molecular pathways modulated in depressed women compared with controls, with a main association with increased B cell activity, while history-only women showed 52 pathways differentially modulated compared with controls, involving lower cytotoxic T cell activity and higher pro-inflammatory pathways activity. Conversely, depressed women showed a differential modulation of 75 pathways, compared with history-only women, associated with increased activity of allo- and auto-immunity and pro-inflammatory pathways. Overall, our results suggest a main role of immunity within the context of perinatal depression, and of a differential modulation of specific immune processes underlying the development of depression and the associated risk.

AB - During pregnancy multiple biological systems undergo consistent modifications, in particular the hormonal axes and the immune system. Moreover, while it is well known that pregnant women suffering from depression show alterations in these systems, the exact underlying mechanisms are still not clear. For this reason, in this study, we explored the blood transcriptomic profile and related pathways in 41 pregnant women with a current diagnosis of depression, 23 pregnant women, who were not depressed in pregnancy but, because of a history of depressive episodes, were considered at high risk of developing antenatal depression (history-only), and 28 pregnant women who had never experienced depression in their life, including the current pregnancy. Based on resulting differentially expressed genes, we identified 28 molecular pathways modulated in depressed women compared with controls, with a main association with increased B cell activity, while history-only women showed 52 pathways differentially modulated compared with controls, involving lower cytotoxic T cell activity and higher pro-inflammatory pathways activity. Conversely, depressed women showed a differential modulation of 75 pathways, compared with history-only women, associated with increased activity of allo- and auto-immunity and pro-inflammatory pathways. Overall, our results suggest a main role of immunity within the context of perinatal depression, and of a differential modulation of specific immune processes underlying the development of depression and the associated risk.

UR - https://www.scopus.com/pages/publications/105001473783

U2 - 10.1038/s41398-025-03309-3

DO - 10.1038/s41398-025-03309-3

M3 - Article

C2 - 40157905

AN - SCOPUS:105001473783

SN - 2158-3188

VL - 15

JO - Translational psychiatry

JF - Translational psychiatry

IS - 1

M1 - 110

ER -