Antidepressant use during pregnancy and the neurodevelopmental effects on the offspring

Depressive symptoms frequently occur during pregnancy and can tremendously affect the developing child. The number of women suffering from depression during pregnancy in Norway doubled in the last 15 years. Over the last years, antidepressants have gained acceptance as medication during pregnancy, which resulted in an increase in the prescription rate in pregnant women. However, antidepressants can cross the placenta and thereby affect the development of the fetus and newborn. Moreover, the potential effect of the drugs on the progeny may be mediated also by a change in the dynamic of the mother-infant relationship. Unfortunately, the developmental effects of antidepressant exposure during pregnancy on the fetus and mother-infant interaction are poorly documented. This project aims to investigate the biological mechanisms and behavioral effects of AD treatment on the offspring throughout lifetime: in juvenile ages, adolescent ages, and at adulthood including maternal behavior. We evaluate the effects on depressive-, anxiety-, and social-emotional behavior. In addition, the project aims to study the influences of multiple life-events on the behavioral outcomes in the offspring. The first part of this project uses a seminatural environmental approach in which rats live in groups and can freely express their full repertoire of behavior, thereby mimicking the real-life environment of children. The effects of AD use during pregnancy on the offspring are investigated in a social context, in which the consequences of environmental influences and life-events can be determined. In the second part, more traditional test set-ups are used to study the effects on social behavior in more detail. Additionally, we will monitor the circulating levels of the AD along time in order to evaluate the administration efficacy and calculate the level of AD passively delivered to the offspring. Ultimately, the results of this project will be beneficial for human health by opening up new strategies for biomedical research and therapeutic applications. This project will need a maximum of 1059 Wistar rats (522 males and 537 females, from which 113 mothers, 98 fathers, and 848 offspring), which is carefully calculated with a power analysis. The severity category in this proposal is expected to be moderate. This kind of experiments cannot be replaced by other models. First of all, there are no methods to study brain mechanisms in humans at such a detailed level. Second, computer simulations or in vitro studies are too simplified compared to the reality. Finally, only in living animals it is possible to study these complex behavioral systems.