Researchers at The Scripps Research Institute (TSRI) have discovered a new target for treating major depressive disorder.

The research shows that individuals with high levels of an enigmatic receptor called GPR158 may be more susceptible to depression following chronic stress. "The next step in this process is to come up with a drug that can target this receptor," said senior author of the study Kirill Martemyanov, from The Scripps Research Institute (TSRI) in the US. The researchers zeroed in on GPR158 as a player in depression after discovering that the protein is elevated in people with major depressive disorder.

To better understand GPR158's role, the scientists studied male and female mice with and without GPR158 receptors. Behavioural tests revealed that both male and female mice with elevated GPR158 show signs of depression following chronic stress. On the flip side, suppression of GPR158 protects mice from developing depressive-like behaviours and make them resilient to stress. For the study, published in the journal eLife, the researchers also examined why GPR158 has these effects on depression.

The team demonstrated that GPR158 affects key signaling pathways involved in mood regulation in the region of the brain called prefrontal cortex, though the researchers emphasised that the exact mechanisms remain to be established. The researchers explained that GPR158 is a so-called "orphan receptor" -- which gets its name because its binding partner/partners are unknown -- with a poorly understood biology and mechanism of action. GPR158 appears to work downstream from other important brain systems, such as the GABA, a major player in the brain's inhibitory control and adrenergic system involved in stress effects.