Major depressive disorder (MDD) is considered a major global health burden, being the single largest contributor to global disability and suicides. Because of its complex multifactorial nature and the variety of symptoms observed in this disorder, still around 50% of MDD patients show no or incomplete response to pharmacological therapies. In this regard, studying the molecular interactions and risk factors of MDD is a key step to improve our knowledge of the etiology and the differences in the treatment response between patients. This thesis aimed to investigate the contribution of several underlying biological processes on the development of depressive behavior in animal models, such as steroidal hormone and monoamine signaling and neuroinflammation. We found that PET imaging is a useful tool to study the effects of sex hormones in the brain in a menopausal animal model, but that chronic stress was not a strong risk factor for developing depressive symptoms in this model. In addition, we showed in a stress model of depression that repeated social defeat induced neuroinflammation, but that this effect was not counteracted by the fast antidepressant ketamine or caffeine. In this animal model, we also showed that social stress caused delayed changes in dopaminergic and serotonergic transmission when depressive symptoms had already resolved. Finally, we observed that antidepressant therapy during pregnancy had a detrimental effect on cognition in the offspring. In conclusion, this thesis provides insight in different interactions between systems and risk factors, contributing to the general knowledge of MDD.
|Kwalificatie||Doctor of Philosophy|
|Datum van toekenning||19-apr-2021|
|Plaats van publicatie||[Groningen]|
|Status||Published - 2021|