Sex-specific difference on anxiety- and depressive-like behavior in neuronal growth regulator 1-knockout mice

This study demonstrates that, in Negr1^-/- mice, both sexes show general behavioral alterations. However, female Negr1^-/- mice exhibit greater vulnerability to fear learning impairments and depression-like behavior, whereas males Negr1^-/- mice show heightened anxiety responses. These behavioral differences were associated with opposing ER stress responses and differential apoptotic signaling between the sexes in peripheral tissues. Our findings highlight the importance of considering sex as a biological variable in depression research and suggest that Negr1 plays a crucial role in the sex-specific pathophysiology of psychiatric disorders through complex mechanisms spanning central and peripheral systems.