Bipolar affective disorder, pregnancy and childbirth: clinical characteristics and heredity

Bipolar affective disorder has higher frequency among women of reproductive age and can relapse both during pregnancy and immediately after childbirth. The presence of family history is one of the leading risk factors for bipolar affective disorder. A cross-sectional study was performed as part of a large naturalistic study. It included 81 women with pronounced symptoms of bipolar disorder who required hospitalization. The clinical method included comprehensive assessment of patients in the cohort, assessment of the severity of symptoms and the family history. The results showed that more than 50% of the women were at an average age of 25 years and experienced bipolar affective disorder mostly in the first and third trimester, whereas, in the puerperal period, the risk was highest in the first two weeks after childbirth. There was previous history of bipolar affective disorder in about 50% of the women. In 55.6% of the women, there was family history of bipolar affective disorder. The presence of previous history of bipolar affective disorder, first-degree family history and pregnancy at later age were shown to be risk factors for a new relapse during pregnancy and after childbirth. Clinical expression of manic–psychotic symptoms was more typical of the period of lactation than manic symptoms, which were associated rather with younger age and the period of pregnancy. In the studied cohort of patients, the risk of repeatability of affective episodes was significantly higher with each subsequent pregnancy

Investigation of candidate genes reveals significant statistical epistasis between DISC1 and TPH2 in Bulgarian affective disorder patients

The aim of the present study was to search for joint influence of variants in affective disorder (AD) candidate genes by investigating statistical epistasis. Overall 24 single nucleotide polymorphisms (SNPs) in 9 AD candidate genes were analysed in 304 AD cases (270 bipolar disorder (BD) type I; 29 BD type II; 5 schizoaffective disorder bipolar type, 110 major depressive disorder) and 205 healthy prescreened controls. The results demonstrated statistical epistasis between variants in DISC1, TPH2, CRH, CLOCK, BDNF, ANK3 and SLC6A4. Multiple interactions involving TPH2, both protective and increasing the AD risk, were detected. Protective epistasis surviving Bonferroni correction was observed between DISC1 and TPH2, justifying further analysis, given their role in neurogenesis and synaptic plasticity and serotonin biosynthesis

The First Genomewide Interaction and Locus-Heterogeneity Linkage Scan in Bipolar Affective Disorder: Strong Evidence of Epistatic Effects between Loci on Chromosomes 2q and 6q

We present the first genomewide interaction and locus-heterogeneity linkage scan in bipolar affective disorder (BPAD), using a large linkage data set (52 families of European descent; 448 participants and 259 affected individuals). Our results provide the strongest interaction evidence between BPAD genes on chromosomes 2q22-q24 and 6q23-q24, which was observed symmetrically in both directions (nonparametric LOD [NPL] scores of 7.55 on 2q and 7.63 on 6q; P<.0001 and P=.0001, respectively, after a genomewide permutation procedure). The second-best BPAD interaction evidence was observed between chromosomes 2q22-q24 and 15q26. Here, we also observed a symmetrical interaction (NPL scores of 6.26 on 2q and 4.59 on 15q; P=.0057 and .0022, respectively). We covered the implicated regions by genotyping additional marker sets and performed a detailed interaction linkage analysis, which narrowed the susceptibility intervals. Although the heterogeneity analysis produced less impressive results (highest NPL score of 3.32) and a less consistent picture, we achieved evidence of locus heterogeneity at chromosomes 2q, 6p, 11p, 13q, and 22q, which was supported by adjacent markers within each region and by previously reported BPAD linkage findings. Our results provide systematic insights in the framework of BPAD epistasis and locus heterogeneity, which should facilitate gene identification by the use of more-comprehensive cloning strategies

Genomewide Scan and Fine-Mapping Linkage Studies in Four European Samples with Bipolar Affective Disorder Suggest a New Susceptibility Locus on Chromosome 1p35-p36 and Provides Further Evidence of Loci on Chromosome 4q31 and 6q24

We present the findings of a large linkage study of bipolar affective disorder (BPAD) that involved genomewide analysis of 52 families (448 genotyped individuals) of Spanish, Romany, and Bulgarian descent and further fine mapping of the 1p34-p36, 4q28-q31, and 6q15-q24 regions. An additional sample of 56 German families (280 individuals) was included for this fine-mapping step. The highest nonparametric linkage scores obtained in the fine mapping were 5.49 for 4q31 and 4.87 for 6q24 in the Romany families and 3.97 for 1p35-p36 in the Spanish sample. MOD-score (LOD scores maximized over genetic model parameters) analysis provided significant evidence of linkage to 4q31 and at least borderline significance for the 1p and 6q regions. On the basis of these results and previous positive research findings, 4q31 and 6q24 should now be considered confirmed BPAD susceptibility loci, and 1p35-p36 is proposed as a new putative locus that requires confirmation in replication studies