Third, targeted gene deletion of a repressor of the 5-HT1A receptor gene (Freud-1) in adult 5-HT neurons to up-regulate 5-HT1A autoreceptors, reduces 5-HT neuronal activity and results in a fluoxetine-resistant anxiety and depression phenotype in both male and female mice (Vahid-Ansari et al., 2017). Here, HTR1A is linked to depressive disorder.