A potential interaction between COMT and MTHFR genetic variants in Han Chinese patients with bipolar II disorder

[[abstract]]Bipolar II disorder (BP-II), characterized by recurrent dysregulation of mood, is a serious and chronic psychiatric illness. However, BP-II is commonly under-recognized, even in psychiatric settings. Because dopaminergic disturbance is thought to be involved in the development of bipolar disorder (BPD), it seems essential to investigate dopamine-related genes like the catechol-O-methyltransferase (COMT) gene, which are involved in dopamine metabolism, and the methylenetetrahydrofolate reductase (MTHFR) gene, which may affect COMT methylation and COMT function. The current study examined the association and interaction of the COMT Val158Met and MTHFR C677T variants with BP-II. Nine hundred seventy-eight participants were recruited: 531 with BP-II and 447 healthy controls. The genotypes of the COMT and MTHFR polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism analysis. Logistic regression analysis showed a significant interaction effect of the COMT Val158Met Val/Val genotype and the MTHFR C677T C/T + T/T genotype (P = 0.039) for the protective effect on the odds of developing BP-II. Our findings support preliminary evidence that the COMT and MTHFR genes interact in BP-II, and they imply the connection of both dopaminergic pathways and methylation pathways in the pathogenesis of BP-II

Depression in pregnancy and child development: understanding the mechanisms of transmission

The impact of depression in pregnancy and in the early postpartum period on neonatal and early child development has been well documented. Perinatal depression predicts poorer cognitive function, behavioural development, and emotional regulation in offspring. However, the mechanism through which this occurs requires clarification. This chapter provides a commentary on existing research, particularly that emerging from fetal programming, to consider possible mechanisms for this transmission of risk. This body of literature suggests that the timing of depression across the perinatal period is significant, and should be separated into exposures across each trimester of pregnancy and across the postnatal period with the timing and dose of depressive symptoms being clearly distinguished. Other cofounding exposures are both psychosocial in nature such as anxiety and stress and also teratogenic such as smoking, nutritional deficiencies, and medication exposures. Such confounds need to be carefully considered when interpreting the depression literature. Putative mechanisms through which prenatal depression impacts child development include direct genetic inheritance, shared adverse environments, elevated maternal stress response, alteration in vascular and placental function, and inflammatory pathways. Postnatal pathways have been more substantially investigated and probably involve maternal sensitivity, lower stimulation, and ongoing environmental stressors. The cumulative effect of both prenatal and postnatal factors should be a greater focus of research design in this field. Prevention and intervention models to reduce the deleterious effects of maternal depression in the preconception, antenatal, and postnatal period can be informed by further research on these mechanisms of transmission