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: 13.56). 08/2007; 164(7):1099-104. DOI: 10.1176/appi.ajp.164.7.1099
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5 cM grid with an average genetic coverage of 0.67 cM. Multipoint analyses were conducted across the genome using non-parametric Kong & Cox LOD scores along with Sall statistics for all relative pairs. Suggestive and significant genome-wide thresholds were calculated based on 1000 simulations. Single-marker association tests in the presence of linkage were performed assuming a multiplicative model with a population prevalence of 2%. We identified two genome-wide significant susceptibly loci for BP at 8q24 and 14q32, and a third suggestive locus at 2q13-q14. Within these three linkage regions, the top associated single marker (rs1847694, P = 2.40 × 10−5) is located 195 Kb upstream of DPP10 in Chromosome 2. DPP10 is prominently expressed in brain neuronal populations, where it has been shown to bind and regulate Kv4-mediated A-type potassium channels. Taken together, these results provide additional evidence that 8q24, 14q32, and 2q13-q14 are susceptibly loci for BP and these regions may be involved in the pathogenesis of BP in the Latino population. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 07/2014; 165(6). DOI:10.1002/ajmg.b.32251 · 3.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Major mental disorders including bipolar disorder aggregate in families. There are also non-familial, solitary cases and familial and non-familial cases may differ. Most of the studies regarding familiality in bipolar disorder targeted similar and dissimilar characteristics of the disease within families. There is a lack of studies targeting between subject differences in patients from different families. The aim of this study is to assess and compare clinical characteristics of type I bipolar patients with and without a family history of bipolar disorders. Method: This study was conducted on outpatients of Raşit Tahsin Mood Disorders Centre of Bakırköy Research and Training Hospital. The medical records of 112 participants (69 female, 43 male, mean age: 41.54±11.19, range: 22-75, 64 of which had family history and 48 without family history) with type I Bipolar Disorder were collected. Missing information was obtained by phone interviews from both patients and first degree relatives. Information of the patients without a family history of any psychiatric disorder was checked with a senior family member. Results: Postpartum episode rates, comorbid psychiatric disorders, number of subjects ever had past mixed episodes, and nicotine dependency rates were found to be significantly higher in patients with family history. No significant difference was detected between groups in terms of age, gender, education, age at disease onset, number of episodes, and number of hospitalizations. Conclusions: Comorbidity, postpartum episodes, lifetime mixed episodes, and smoking were found to be higher in patients with family history and thus associated with bipolarity. Postpartum episodes and comorbidities can be expected to be more prevalent in patients with family history. However clinical characteristics should be further investigated in larger samples.
    09/2011; 1(3):110-112. DOI:10.5455/jmood.20110816022359
  • [Show abstract] [Hide abstract]
    ABSTRACT: We sought to determine clinical predictors of postpartum depression (PPD), including the role of medication, in a sample of women followed prospectively during and after pregnancy. Women with a history of mood disorder were recruited and evaluated during each trimester and 1 week, 1 month, and 3 months postpartum. DSM-IV criteria for a major depressive episode were assessed by a psychiatric interview at each time point. Sixty-three women with major depression and 30 women with bipolar disorder entered the study and 75.4 % met DSM-IV criteria for a MDE during pregnancy, postpartum, or both. We modeled depression in a given time period (second trimester, third trimester, or 1 month postpartum) as a function of medication use during the preceding period (first, second, or third trimester). The odds of being depressed for those who did not use medication in the previous period was approximately 2.8 times that of those who used medication (OR 2.79, 95 % CI 1.38-5.66, p = 0.0048). Of 38 subjects who were psychiatrically well during the third trimester, 39.5 % (N = 15) met the criteria for a MDE by 4 weeks postpartum. In women who developed PPD, there was a high rate of a family history of PPD (53.3 %) compared to women who did not develop PPD (11.8 %, p = 0.02). While the use of psychiatric medications during pregnancy reduced the odds of being depressed overall, the use of psychiatric medications during pregnancy may not protect against PPD in women at high risk, particularly those with a family history of PPD.
    Archives of Women s Mental Health 07/2014; 18(1). DOI:10.1007/s00737-014-0432-9 · 1.96 Impact Factor

Full-text (2 Sources)

Available from
May 31, 2014