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Post-partum psychosis and its association with bipolar disorder in the UK: a case-control study using polygenic risk scores

Di Florio, Arianna, Yang, Jessica M. K., Crawford, Karen, Bergink, Veerle, Leonenko, Ganna, Pardinas, Antonio, Escott-Price, Valentina, Gordon-Smith, Katherine, Owen, Michael J., Craddock, Nick, Jones, Lisa, O'Donovan, Michael and Jones, Ian 2021. Post-partum psychosis and its association with bipolar disorder in the UK: a case-control study using polygenic risk scores. The Lancet Psychiatry 8 (12) , pp. 1045-1052. 10.1016/S2215-0366(21)00253-4

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Abstract

Background For more than 150 years, controversy over the status of post-partum psychosis has hindered research and caused considerable confusion for clinicians and women, with potentially negative consequences. We aimed to explore the hypothesis that genetic vulnerability differs between women with first-onset post-partum psychosis and those with bipolar disorder more generally. Methods In this case-control study on first-onset post-partum psychosis and bipolar disorder in the UK, we included 203 women with first-onset post-partum psychosis (defined as a manic, mixed, or psychotic depression episode within 6 weeks of delivery without a psychiatric history) and 1225 parous women with a history of bipolar disorder. Information on women with bipolar disorder was obtained from the Bipolar Disorder Research Network database, and participants were recruited through screening community mental health teams across the UK and via the media and patient support organisations. All were assessed using a semistructured face-to-face psychiatric interview and psychiatric case note review. 2809 women from the general population were recruited via the national UK Blood Services and the 1958 Birth Cohort (UK National Child Development Study) as controls and matched to cases according to genetic ancestry. All self-reported their ethnicity as White and were recruited from across the UK. Polygenic risk scores (PRSs) were generated from discovery genome-wide association studies of schizophrenia, bipolar disorder, and major depression. Logistic regression was used to model the effect of each PRS on diagnosis, and the RRs and ORs presented were adjusted for ten principal components of genetic variation to account for population stratification. Findings 203 women with first-onset post-partum psychosis (median age at interview: 46 years [IQR 37–55]) and 1225 women with bipolar disorder (49 years [41–58]) were recruited between September, 1991, and May, 2013, as well as 2809 controls. Women with first-onset post-partum psychosis had similar bipolar disorder and schizophrenia PRSs to women with bipolar disorder, which were significantly higher than those of controls. When compared with controls, women with first-onset post-partum psychosis had an adjusted relative risk ratio (RR) for bipolar disorder PRSs of 1·71 (95% CI 1·56–1·86, p<0·0001) and for schizophrenia PRSs of 1·82 (1·66–1·97, p<0·0001). The effect sizes were similar when comparing women with bipolar disorder to controls (adjusted RR 1·77 [1·69–1·84], p<0·0001 for bipolar disorder PRSs; 2·00 (1·92–2·08), p<0·0001 for schizophrenia PRSs). Although women with bipolar disorder also had higher major depression PRSs than did controls (1·24 [1·17–1·31], p<0·0001), women with first-onset post-partum psychosis did not differ from controls in their polygenic liability to major depression (0·97 (0·82–1·11), p=0·63).

Item Type: Article
Date Type: Publication
Status: Published
Schools: National Centre for Mental Health (PNCMH)
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier
ISSN: 2215-0366
Date of First Compliant Deposit: 12 July 2021
Date of Acceptance: 5 July 2021
Last Modified: 30 May 2022 16:31
URI: https://orca.cardiff.ac.uk/id/eprint/142524

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