Bipolar disorder in pregnancy and the postpartum

In the first part of my PhD I explored the link between childbirth and mood disorders in a retrospective sample of over 1500 parous women with mood disorders, recruited as part of ongoing molecular generic studies. Around two thirds of participants reported at least one episode of illness during pregnancy or the postpartum. Women with bipolar I disorder reported an approximately 50% risk of a perinatal major affective episode. Risks were lower in recurrent major depression and bipolar II disorder at around 40%. The majority of perinatal episodes occurred within 4 weeks of childbirth. Episodes of mania or psychosis had an earlier onset than those of depression. For bipolar II disorder, onsets of psychiatric episodes were more spread out over the perinatal period with more onsets in pregnancy and later in the postpartum. Moreover, childbirth did not seem to be a specific trigger for the majority of perinatal episodes of bipolar II disorder. Primiparity was associated with postpartum mania/psychosis and unipolar postpartum depression in women who experienced their first lifetime episode within 6 weeks postpartum. My findings raise the possibility of a relationship between postpartum mood disorders and other disorders influenced by parity, such as pre-eclampsia. In the second part of my PhD I designed and piloted a prospective study aimed i) to replicate and ii) to extend the findings on the retrospective sample, exploring the influence of a range of variables on the vulnerability to develop an episode of severe illness in pregnancy or the postpartum. Over 14 months of recruitment 19 women completed the follow-up assessment. To capture the clinical complexity of bipolar disorder in pregnancy and the postpartum period very large scale longitudinal studies are needed. These studies must be based on a strong collaboration with the NHS

The birth of a psychiatric orphan disorder: postpartum psychosis [Correspondence]

Feb 29 is officially marked as Rare Disease Day. Hitherto, more than 5800 rare diseases have been officially recognised, but none of these is an adult psychiatric disorder. In this leap year (2016), postpartum psychosis is included, for the first time, in the list curated by Orphanet, the reference portal for information on rare diseases

Genetic risk for bipolar disorder and psychopathology from childhood to early adulthood

Background: Studying the phenotypic manifestations of increased genetic liability for Bipolar Disorder (BD) can increase understanding of this disorder. Aims: We assessed whether genetic risk for BD was associated with childhood psychopathology and features of hypomania in young adulthood within a large population-based birth cohort. Methods: We used data from the second Psychiatric Genetics Consortium Genome Wide Association Study (GWAS) for Bipolar Disorder to construct a polygenic risk score (PRS) for each individual in the Avon Longitudinal Study of Parents and Children (ALSPAC). Linear and logistic regression models were used to assess associations between the BD-PRS and emotional/behavioural difficulties, attention deficit hyperactivity disorder (ADHD) and borderline personality disorder (BPD) traits in childhood, as well as hypomania in early adulthood (sample sizes from 2654 to 6111). Results: The BD-PRS was not associated with total hypomania score, but was weakly associated with a binary measure of hypomania (OR = 1.13, 95%CI 0.98,1.32; p = 0.097), and particularly at higher hypomania symptom thresholds (strongest evidence OR = 1.33, 95%CI 1.07, 1.65; p = 0.01). The BD-PRS was also associated with ADHD (OR = 1.31, 95%CI 1.10, 1.57; p = 0.018), but not with other childhood psychopathology. Limitations: The PRS only captures common genetic variation and currently explains a relatively small proportion of the variance for BD. Conclusions: The BD-PRS was associated with ADHD in childhood, and weakly with adult hypomania, but not with other psychopathology examined. Our findings suggest that genetic risk for BD does not appear to manifest in childhood to the same extent as schizophrenia genetic risk has been reported to do

Progesterone and plasma metabolites in women with and in those without premenstrual dysphoric disorder

Background The molecular mechanisms underpinning the progesterone‐triggering mood symptoms in women with premenstrual dysphoric disorder (PMDD) are unknown. Cell metabolism is a potential source of variability. Very little is known about the effect of progesterone sensitivity on the metabolome. In this study, we aimed to characterize the effects of progesterone on the global metabolic profile and explore the differences between women with PMDD and controls. Methods Plasma was obtained from 12 women with prospectively confirmed PMDD and 25 controls under two hormone conditions: (1) gonadal suppression induced by leuprolide acetate (3.75 mg IM monthly) and (2) add‐back phase with leuprolide and progesterone (200 mg twice daily by vaginal suppository). The global metabolic profile was obtained using liquid and gas chromatography followed by mass spectrometry. Differences between groups and time points were tested using repeated measures analysis of variance. The false discovery rate was calculated to account for multiple testing. Results Amino acids and their derivatives represented 78% (28/36) of the known compounds that were found in significantly lower plasma concentrations after progesterone administration than during gonadal suppression. The concentration of tyrosine was nominally significantly decreased after progesterone add‐back in controls, but not in cases (P = 0.02). Conclusion Plasma levels of some amino acids are decreased in response to progesterone. Albeit preliminary, evidence further suggests that progesterone has a different effect on the metabolic profiles of women with PMDD compared to controls. Further research is needed to replicate our findings in a larger sample and to identify the unknown compounds, especially those differentially expressed

HPA axis reactivity to pharmacologic and psychological stressors in euthymic women with histories of postpartum versus major depression

It is unclear whether women with a history of postpartum depression (PPD) have residual, abnormal hypothalamic-pituitary-adrenal (HPA) axis reactivity, as has been reported in major depression (MDD). Further unclear is whether the abnormalities in HPA axis reactivity associated with MDD represent a stable, underlying predisposition or a state-dependent phenomenon. This study sought the following: (1) to determine if euthymic postpartum women with a history of depression have an abnormal HPA axis reactivity to pharmacologic and psychological challenges and (2) to compare HPA reactivity in women with histories of PPD versus MDD. As a secondary objective, we wanted to determine the influence of trauma history on HPA axis function. Forty-five parous (12–24 months postpartum), euthymic women with history of MDD (n = 15), PPD (n = 15), and controls (n = 15) completed pharmacologic (dexamethasone/corticotropin-releasing hormone (CRH) test [DEX/CRH]) and psychological (Trier social stress test [TSST]) challenges during the luteal phase. Outcome measures were cortisol and adrenocorticotropic hormone (ACTH) response after DEX/CRH, and blood pressure, heart rate, epinephrine, norepinephrine, and cortisol response during the TSST. All groups had robust cortisol and ACTH response to DEX/CRH and cortisol response to TSST. Groups did not differ significantly in cortisol or ACTH response to DEX/CRH or in blood pressure, heart rate, epinephrine, norepinephrine, or cortisol response to TSST. Cortisol/ACTH ratio did not differ significantly between groups. Trauma history was associated with decreased cortisol response to DEX/CRH in women with histories of MDD, which was not significant after correction (F8,125, p = 0.02, Greenhouse-Geisser corrected p = 0.11). Currently euthymic women with histories of MDD or PPD did not demonstrate residual abnormal stress responsivity following administration of either a pharmacologic or psychological stressor