Disentangling the Genetic Landscape of Peripartum Depression: A Multi-Polygenic Machine Learning Approach on an Italian Sample

Published: 3 December 2025| Version 1 | DOI: 10.17632/3ynpdxkr4p.1
Contributors:
Yasmin Harrington, Lidia Fortaner Uya, Marco Paolini,
, Cristina Lorenzi, Sara Spadini, Elisa Maria Teresa Melloni, Elena Agnoletto, Raffaella Zanardi, Cristina Colombo, Francesco Benedetti

Description

Using a multi-polygenic score approach, we characterized the relationship between genome-wide information and the history of PPD in patients with mood disorders, with the hypothesis that multiple polygenic risk scores (PRSs) could potentially influence the development of PPD. The PLS linear regression in the whole sample defined a model explaining 27.12% of the variance in the presence of PPD history, 56.73% of variance among MDD, and 42.96% of variance in BD. Our findings highlight that multiple genetic factors related to circadian rhythms, inflammation, and psychiatric diagnoses are top contributors to the prediction of PPD. Specifically, in MDD, the top contributing PRS was monocyte count, while in BD, it was chronotype, with PRSs for inflammation and psychiatric diagnoses significantly contributing to both groups.

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Institutions

Ospedale San Raffaele

Categories

Psychiatry, Machine Learning, Mood Disorder, Postpartum Depression, Polygenic Score

Funders

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