Of mice and men: a translational study investigating depressive-like behavior induced by early life adversities

Depression is a widely spread disorder that has a great cost both in terms of health to the individual and to society. Among the main risk factors for depression are Early Life Adversities (ELA), which occur in a time window of great development for the brain, creating non-linear developmental trajectories that can predispose to psychopathology. The objective of this thesis is to investigate ELA-related depression, splitting ELA into two macro categories: the alteration of the attachment bond and childhood trauma, to understand if these experiences induce differences in the depressive-like phenotype and if these differences are accompanied by different neurobiological alterations. To achieve this objective, we first investigate the presence of ELA in a non-clinical population and carry out a regression analysis to observe any relationships between the type of ELA lived and the presence of depressive symptoms. In addition, we analyze the levels of Oxytocin in plasma. Next, to investigate the neurobiological differences between Trauma and Attachment Bond Alteration, we leverage the preclinical model. Here, we use two mouse models of ELA in male mice of the inbred strain C57BL/6J: the Repeated Cross Fostering (RCF) model, which reproduces the alteration of the attachment bond in humans, and the Scarcity model, which mimics a Neglect condition (therefore of traumatic experience) in humans. In these two models, we first evaluate the quality of maternal care to highlight aspects related to the presence or absence of abuse in pups. Then, we investigate the attachment behavior of pups towards their mothers. We also evaluate the depressive-like behaviors, both in adolescence and adulthood, in these animals. Finally, we analyze the alteration of two different social neuropeptides within the mesocorticolimbic circuit: Oxytocin and Endogenous Opioids. In fact, these two neuropeptides are modulated by ELA and are altered in subjects affected by depression.