TPH2 and major depressive disorder: Tph2−/− mice, lacking brain 5-HT synthesis and Tph2+/− mice, with up to 30 % reduction of 5-HT concentrations in the raphe nuclei (Gutknecht et al. 2012; Waider et al. 2013), were subjected to unpredictable chronic mild stress (CMS (Willner 2005)) to assess the impact of deficient serotonergic neurotransmission in the brain on anxiety- and depression-like behavior, conditioned fear responses, and aggression as well as hypothalamic-pituitary-adrenal (HPA) axis reactivity and adaptation to CMS.