The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring

Epigenetic mechanisms are important for regulating gene expression and differentiation during early life. Recent studies have highlighted the possible impact of environmental factors on epigenetic characteristics during development. In utero exposure to chemicals, nutrition, or social factors may change the methylation status at CpG-rich regions of gene promoter regions, causing permanent modification of gene expression patterns [1-3]. Such alterations may lead to increased risk of chronic diseases, including mental disorders, diabetes, cardiovascular diseases and cancer [4-6].Maternal depression, and associated drug use are common exposures to the developing fetus. The prevalence of depression in pregnant women is greater than ten percent [7], and the rate of prescriptions for mood regulators reported among pregnant women in the U.S. has increased threefold, from 1998 to 2005 [8]. Co-occuring adverse factors include: inadequate nutrition intake or insufficient weight gain, and cigarette smoking [9]. It has been shown that in utero exposure to maternal depression adversely affect fetal growth [10,11], fetal neurobehavioral development, or childhood behavior [12-15]. Exposure to SSRIs (Selective Serotonin Reuptake Inhibitors) has been associated with congenital malformations [16-20], respiratory distress, or neurobehavioral symptoms in newborns [21,22]. As a consequence, treatment of psychiatric disorders during pregnancy is controversial; the fetus is either exposed to the psychotropic drugs or to the disease itself.The biological mechanisms behind the adverse fetal developmental consequences of antidepressant use of the mother or exposure to maternal depression are unclear. Evidence suggests that mood disorders or antidepressant medicines are associated with modulation of epigenetic regulation [23]. Adverse social environments can induce altered DNA methylation at the promoter of the glucocorticoid receptor gene in the rat hippocampus [24,25,2]. Aberrant methylatio