Adult hippocampal neurogenesis (AHN) regulates hippocampal-dependent functions and is targeted by physiological aging and neurodegenerative conditions. Patients with neuropsychiatric disorders show hippocampal abnormalities that might be related to changes in AHN. Here, we sought to determine whether major depression, schizophrenia, and bipolar disorder threaten the integrity of human AHN and the homeostasis of the dentate gyrus (DG) neurogenic niche-a specialized microenvironment in which new neurons grow. Our results show that the initial and intermediate stages of AHN, as well as distinct components of the niche, are selectively affected in these disorders. Demographics and various lifestyle-related factors (such as the consumption of alcohol and drugs of abuse) modulate both AHN and the cells that compose the niche, not only in patients with these disorders but also in neurologically healthy control individuals. These data might be relevant for the design of future strategies to treat and prevent mental health conditions.

The mammalian hippocampus generates new dentate granule cells (DGCs) throughout life. This process, named adult hippocampal neurogenesis (AHN), participates in hippocampal functions such as memory and mood regulation. Moreover, AHN is impaired in mouse models and patients with neurodegenerative and psychiatric disorders. Additionally, physiological aging targets AHN and the integrity of the hippocampal neurogenic niche. This perspective review aims to discuss the regulation of human AHN in patients with neurodegenerative and psychistric conditions. Moreover, we will address key adaptations of human AHN and the neurogenic niche in response to physiological aging.