Sex Differences in Depression: Adult Cytogenesis as Potential Target for Precision Psychiatry

Sex differences are increasingly recognized as key determinants of vulnerability, clinical presentation, and treatment response in depression. Rather than arising from a single mechanism, these differences emerge from the interplay of multiple biological and non-biological factors. Converging evidence points to the hippocampus as a central region where these processes intersect, with adult neurogenesis and astrogliogenesis representing a potential mechanistic link between sex-specific biological factors and behavioral outcomes in depression. In this review, we integrate findings from human studies and preclinical models to examine how sex impacts depression while considering the multiple origins of sexual differentiation in the central nervous system. We discuss the importance of studying sex as a biological variable and acknowledge current limitations in the field. Finally, we highlight how cytogenic processes in the adult hippocampus are modulated in a sex-dependent manner, how their disruption may contribute to the pathophysiology of depression, and their potential role in precision psychiatry. Adult cytogenesis provides a promising target for developing therapeutic strategies aimed at promoting the integration of these cells in neural circuits, which may counterbalance the cellular impairments observed in stress-induced depression, representing a therapeutic avenue for this disorder.