Targeting a stress protein may prevent the effects of early trauma

Early life adversity (ELA), such as childhood trauma, abuse, or neglect, is a major risk factor for developing psychiatric disorders, including depression, anxiety, and post-traumatic stress disorder later in life. However, how these experiences become biologically embedded in the brain has remained unclear. In a new study, the researchers show that pharmacological intervention during a critical developmental period can prevent long-term effects of early stress in a mouse model.

Interrupting social subordination with SAFit2

The study focused on the FKBP5 gene and its encoded protein, FKBP51, a well-established regulator of the body's stress hormone system and heavily implicated in psychiatric vulnerability.

To investigate the effects of early trauma on social dynamics, the researchers used a mouse model of early-life adversity combined with an advanced computer-vision-based tracking system called the Social Box. This semi-naturalistic living environment allowed for high-resolution, continuous analysis of complex social interactions within a group context.

The team discovered that mice exposed to early adversity developed profound, persistent deficits in social behaviour, manifesting as social subordination during both adolescence and adulthood. These stressed mice were disproportionately pushed into the lowest ranks of their social hierarchies. Strikingly, when SAFit2, a highly selective and brain-penetrant FKBP51 inhibitor, was administered during the early adversity period, these behavioural impairments were rescued. The treated mice successfully developed normative social hierarchy dynamics, showing no difference from non-stressed controls.