Bipolar Affective Puerperal Psychosis: Genome-Wide Significant Evidence for Linkage to Chromosome 16

Department of Psychological Medicine and Neurology, Cardiff University, Cardiff, Wales, United Kingdom
American Journal of Psychiatry (Impact Factor: 12.3). 08/2007; 164(7):1099-104. DOI: 10.1176/appi.ajp.164.7.1099
Source: PubMed


Vulnerability to the triggering of bipolar episodes by childbirth aggregates in families and may define a genetically relevant subtype of bipolar disorder. The authors conducted a search by systematic whole genome linkage scan for loci influencing vulnerability to bipolar affective puerperal psychosis.
The authors selected families with bipolar disorder from their previous bipolar disorder genome scan, in which there was at least one family member with a manic or psychotic episode with an onset within 6 weeks of delivery. Individuals were coded as affected if they had been diagnosed with bipolar I disorder; bipolar II disorder; or schizoaffective disorder, bipolar type, according to DSM-IV. A total of 36 pedigrees contributed 54 affected sibling pairs to the cohort. A genome scan with 494 microsatellite markers was analyzed using GENEHUNTER and MAPMAKER/SIBS.
A genome-wide significant linkage signal was observed on chromosome 16p13, and a genome-wide suggestive linkage was observed on chromosome 8q24. No significant or suggestive linkage was observed in these regions in our original bipolar scan.
This study identifies chromosomal regions that are likely to harbor genes that predispose individuals to bipolar affective puerperal psychosis. The identification of susceptibility genes would enhance understanding of pathogenesis and offer the possibility of improvements in treatment and risk prediction.

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    • "Accordingly, there is evidence for the familiarity of postpartum episodes but specific genes have not yet been identified (Jones et al. 2007; Byrne et al. 2014). Despite extensive efforts, a definitive pathophysiology for postpartum psychiatric disorders has remained elusive . "
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    ABSTRACT: Recent evidence suggests that postpartum psychiatric episodes may share similar etiological mechanisms with immune-related disorders. Pre-eclampsia is one of the most prevalent immune-related disorders of pregnancy. Multiple clinical features are shared between pre-eclampsia and postpartum psychiatric disorders, most prominently a strong link to first pregnancies. Therefore, we aimed to study if pre-eclampsia is a risk factor for first-onset postpartum psychiatric episodes. We conducted a cohort study using the Danish population registry, with a total of 400 717 primiparous women with a singleton delivery between 1995 and 2011. First-lifetime childbirth was the main exposure variable and the outcome of interest was first-onset postpartum psychiatric episodes. The main outcome measures were monthly incidence rate ratios (IRRs), with the period 11-12 months after birth as the reference category. Adjustments were made for age, calendar period, reproductive history, and perinatal maternal health including somatic and obstetric co-morbidity. Primiparous women were at particularly high risk of first-onset psychiatric episodes during the first month postpartum [IRR 2.93, 95% confidence interval (CI) 2.53-3.40] and pre-eclampsia added to that risk (IRR 4.21, 95% CI 2.89-6.13). Having both pre-eclampsia and a somatic co-morbidity resulted in the highest risk of psychiatric episodes during the 3-month period after childbirth (IRR 4.81, 95% CI 2.72-8.50). We confirmed an association between pre-eclampsia and postpartum psychiatric episodes. The possible explanations for this association, which are not mutually exclusive, include the psychological impact of a serious medical condition such as pre-eclampsia and the neurobiological impact of pre-eclampsia-related vascular pathology and inflammation.
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    • "In addition to symptoms of mania and depression, some patients with BD I may express psychotic features during mood episodes, suggesting possible overlap between psychotic and affective disorder phenotypes. Further, the distinction between schizoaffective disorder and BD with psychotic features is not always clear, and it is possible that BD I and SZ represent two ends of a spectrum of disease with shared underlying genetic and cognitive traits, with BD I on the affective side and SZ on the psychotic side, and schizoaffective disorder and BD I with psychotic episodes in the intermediate zone (Ghaemi, Wingo, Fikowski, & Baldessarini, 2008; Jones et al., 2007). Given this possible overlap, there may be unique neurocognitive markers that distinguish BD I with psychosis (BD+) from BD I without psychosis (BD-) and indeed, there is a growing body of research that BD+ has been associated with greater neurocognitive impairment (Albus et al., 1996; Kravariti, Dixon, Frith, Murry, & McGuire, 2005). "

    Full-text · Chapter · Jan 2013
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    • "was associated with an almost four times risk of puerperal psychosis (OR=3.9), an effect that increased when the phenotype was restricted to women who had experienced multiple episodes (Coyle et al, 2000); recent work has shown linkage with chromosomes 16p13 and 8q24 (Jones et al, 2007). "

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