Abstract
Postpartum Psychosis (PP) is a severe and understudied perinatal mental illness which disproportionately affects women with bipolar disorder (BD). A relationship between sleep disturbance and PP is often assumed, but is poorly understood. From a cohort of 2099 individuals with BD, 343 parous women were identified and screened for perinatal psychiatric complications. We compared 117 women who developed PP with 226 who did not. Polygenic Risk Scores (PRS) for BD, schizophrenia, insomnia, short sleep, long sleep, sleep efficiency and sleep duration were computed using PRS-CS. Logistic regression was used to model the effect of each PRS on PP. Higher PRS for insomnia and short sleep were associated with reduced risk of PP. Individuals in the lowest decile for insomnia PRS (RR 1.96, 95% CI 1.25-3.07, p = 3.50 × 10⁻³) and short sleep PRS (RR 2.23, 95% CI 1.40-3.54, p = 7.94 × 10⁻⁴) had approximately double the risk of PP than individuals in the highest decile. The other PRS were not associated with PP. Mendelian Randomisation analyses did not support a causal relationship between sleep traits and PP. However, we demonstrate that the integration of PRS with bipolar subtype can improve prediction accuracy. Individuals with genetic vulnerability to insomnia or short sleep may develop a heightened tolerance to sleep disruption earlier in life, mitigating the impact of childbirth on mood. These findings suggest that genetic susceptibility to sleep disturbance may be important in the aetiology of PP, offering a new potential avenue for risk stratification and targeted prevention.
Data availability
The GWAS summary statistics used for these analyses is publicly available through the original publications for the different phenotypes of interest: bipolar disorder [17], schizophrenia [64], insomnia [53], short and long sleep [54], sleep efficiency and sleep duration [55]. The participant data set used for this study as well as the code for the analyses conducted is available upon request.
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Acknowledgements
The authors would like to gratefully acknowledge all DNA Polymorphisms In Mental illness (DPIM) study participants for their contribution to this work. Participant recruitment was funded by the Medical Research Council (MRC grant code G1000708), the Neuroscience Research Charitable Trust, the Camden and Islington NHS Foundation Trust, a research lectureship from the Priory Hospitals and the National Institute for Health and Care Research (NIHR) Mental Health Research Network (MHRN). The study also received support from Bipolar UK (formerly the UK Manic Depression Fellowship). Genotyping was funded by the Stanley Center for Psychiatric Research at the Broad Institute. Parts of the analyses were supported by a project that has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant agreement No. 948561). CP is supported by the Rosetrees Trust and the Elizabeth Garrett Anderson Hospital Charity. DS is supported by the NIHR. AM, NB and SE are supported by the NIHR University College London Hospitals Biomedical Research Centre funding scheme.
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CP led on study design and data analysis in partnership with AM, who is the chief investigator of the DPIM Study. All other authors supported data analysis and provided guidance based on their individual areas of specialist expertise. SHE and NM contributed specialist input in sleep medicine; OP and NB contributed clinical psychiatry expertise; KK provided guidance on data analysis and Mendelian Randomisation; DS contributed expertise in obstetrics and perinatal complications. CP instigated and wrote this manuscript. All authors reviewed this, provided feedback and approved the final submission.
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NM has received speaker fees from Idorsia pharmaceuticals. SE has received honoraria for educational activities from Eisai, Fidia, Lincoln, and UCB pharma. CP, OP, KK, NB, DS and AM have no conflicts of interest to declare.
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Petrosellini, C., Eriksson, S.H., Meyer, N. et al. Postpartum Psychosis: could genetic vulnerability to insomnia or short sleep duration be protective?. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-03856-3
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DOI: https://doi.org/10.1038/s41398-026-03856-3