Post-partum psychosis: birth of a new disorder?

Women who experience abrupt onset of affective and psychotic symptoms within 2 weeks of childbirth are considered to have post-partum psychosis but anyone seeking advice on the clinical management of this condition will encounter a problem—neither ICD nor the DSM recognises post-partum psychosis as a distinct disorder. Cases are assigned as general mania or psychotic depression with a perinatal onset specifier. This makes targeted treatment difficult. Patrick McGorry has been fascinated by post-partum psychosis since treating several women with this disorder early in his career. “The clinical picture and its aftershocks were very dramatic and qualitatively different from textbook schizophrenia and manic psychosis. Apart from nosological introspections, the most obvious aspect to strike me, which seems to have been neglected over the decades, was the tight temporal relationship of the onset of the mental changes to birth, and the dramatic biological changes that occur around that time. This aetiological clue remains one of the gold nuggets that is yet to be picked up and minted.” In The Lancet Psychiatry, Arianna DiFlorio and colleagues pursue this aetiological clue by exploring whether women with first-onset post-partum psychosis could be distinguished genetically from women with bipolar disorder who had an episode of post-partum psychosis in the context of their pre-existing illness. They recruited women from the UK and calculated polygenic risk scores using data from genome-wide association studies of schizophrenia, bipolar disorder, and major depression. Compared with controls, women with first-onset post partum psychosis and women with bipolar disorder both had greater genetic risk for schizophrenia and for bipolar disorder, but only the women with bipolar disorder had greater risk for depression.

This study has implications for clinical practice and research. In terms of prognosis and treatment, previous clinical studies suggested that women with first-onset post-partum psychosis had more favourable long-term outcomes than women with post-partum psychosis in the context of pre-existing bipolar disorder and that women whose illness is confined to the post-partum period do not need prophylaxis during subsequent pregnancies. DiFlorio and colleagues’ study corroborates these findings with biological evidence. For further progress in being able to properly identify and treat women at risk

of postnatal psychosis, researchers need to start asking women about their experiences of post-partum psychosis. The absence of such data precluded replication of these findings in existing cohorts, such as UK Biobank. In particular, replication is needed in more ethnically diverse populations. Only 2·2% of women in the Bipolar Disorder Research Network used in this study identified themselves as non-White vs about 85% in the general population, so DiFlorio and colleagues restricted genotyping to those who identified as White. Similarly, non-White populations are underrepresented in GWAS databases. More balanced representation will require outreach and education, which needs to be considered in planning and funding. Additionally, treatment response is not well covered in genomics databases. One good example is the work by the International Consortium on Lithium Genetics which has examined the effect of schizophrenia polygenic risk scores on lithium response, but not of those of major depression.

In terms of diagnosis, the findings of DiFlorio and colleagues have both specific and general implications. Building on evidence from clinical, epidemiological, and family studies, the authors hypothesise that first-onset post-partum psychosis identifies a group of women with a genetic vulnerability that differs from that of women with bipolar disorder more generally. This suggests that postpartum psychosis should be included as a separate disease entity in the DSM and ICD. Of wider interest is the demonstration that the creation of diagnostic subtypes, for example by the addition of a perinatal onset specifier, is misleading. Many psychiatric disorders are poorly defined using broad and optional criteria. So far, genomic association studies have been similarly imprecise, showing considerable overlap among genes and disorders. Rather than looking to genomics for leads, DiFlorio and colleagues used polygenic risk scores to explore differences between groups suspected to differ clinically and were able to identify a distinct subgroup.

As Samantha Meltzer-Brody says, “This study provides a critical piece of biologic evidence in support of post partum psychosis being characterized as a distinct entity that differs from both bipolar disorder and major depression. This has important implications for diagnosis and treatment that will improve the care of patients who suffer with this devastating condition.“