depreg · Antidepressants during pregnancy: underlying mechanisms associated with neurodevelopmental outcome

Antidepressants during pregnancy: underlying mechanisms associated with neurodevelopmental outcome

Problem being addressed About 20% of the current pregnant women are depressed or suffer from depressive symptoms during pregnancy. Up to 5% percent of these women suffer from major depression and cannot operate without antidepressant treatment. Both depressive symptoms during pregnancy as well as using antidepressants during pregnancy can negatively impact the behavioral development and health of the child. It is difficult to tell whether taking antidepressants during pregnancy increases the risk for the developing child, and if so whether we can unravel the mechanisms that are involved in these risks and use this information for new therapeutic applications. Therefore the overall aim of this project is to identify molecular mechanisms and behavioral alterations in the offspring due to antenatal depression, antidepressant treatment during pregnancy, and their combination. Importance for society Currently, little information is available about the underlying mechanisms contributing to the critical implications for the health of the child due to depression during pregnancy, antidepressant treatment during pregnancy and their combination. The current project focused especially on the molecular mechanisms (gene expression and epigenetics in the brain) underlying the behavioral alterations in the offspring. So far, genetic studies have not revealed new targets for the treatment of depression. As this project focuses on epigenetic modulations of altered genes due to depression or antidepressant use during pregnancy, new targets for therapeutic applications may be discovered. Overall objectives The objectives of the proposal were to identify the effects of depression during pregnancy, antidepressant treatment use during pregnancy, and their combination on: 1. behavior of the offspring, 2. gene expression patterns of the fetal brain (offspring), and 3. epigenetic profile adult brain and blood plasma (offspring) of candidate genes found in objective 2. Because it is difficult to discern between the effects of the drug and the effects of the depression itself in humans, we used a rat model for depression. These rats were treated with an antidepressant drug or a placebo during pregnancy and the lactation period. This period was chosen to mimic the developmental stages of the human brain. Besides these rats, also healthy rats were treated with antidepressants to find out what the effect of only antidepressant use during pregnancy was on the offspring. We investigated the behavioral alterations and molecular mechanism in the offspring from mothers that were: A) Healthy rats treated with placebo B) Healthy rats treated with antidepressants C) Depressed treated with placebo D) Depressed treated with antidepressants (mimicking the human situation)

Data: CORDIS, © European Union