A new study has possibly found a new target for treating major depressive disorder that is said to affect 16 million American adults.
According to the study individuals with high levels of an enigmatic receptor called GPR158 may be more susceptible to depression following chronic stress. Researchers published their findings in journal eLife wherein they call for urgent requirement for new drug targets in major depressive disorder. Current pharmacological treatments for depression can take a month to start working–and they don’t work in all patients.
Researchers concentrated 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.
Behavioral 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 behaviors and make them resilient to stress.
Next, the researchers 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 emphasized that the exact mechanisms remain to be established.
Researchers explains 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.
The study also offers a potential clue to why some people are more susceptible to mental illness. Because mice without GPR158 don’t alter their behavior after chronic stress, the researchers concluded these mice were naturally more resilient against depression. Their genetics, or gene expression, offer a layer of protection.