A new biomarker that can identify depression patients experiencing a lack of motivation could be used to tailor anti-depressant drugs to patients, depending on the specific symptoms of the disease they display.

Depression is one of the most common psychiatric disorders in the world and affects about 9% of the US population. However, as less than half of patients respond to therapy there is an urgent need for a new class of anti-depressants tailored to different symptoms of the disease.

Three of the most common symptoms for human depression are anxiety, lack of motivation and lack of pleasure. Not all patients display all symptoms of the disease, and the study authors stress the need to ‘move away from considering depression as a single or homogeneous disease.  In this study, researchers attempted to understand the biological mechanisms underpinning the lack of motivation symptom.

In a previous study, depression patients who had been so far resistant to drug treatment experienced improvement in their symptoms after electrical simulation in the lateral habenula (LHb) region of their brains. It was found that mice experiencing chronic stress displayed an increase of neural activity in their LHb cells, which caused changes in the VTA DA neurons. This led to a reduced motivation in the mice, but interestingly no symptoms of anxiety or loss of pleasure; suggesting that the LHb isn’t associated with the other major depression symptoms.

Multiple genes were found to be upregulated in mice experiencing chronic stress, and the researchers are now investigating if knocking them out with CRISPR/cas-9 could improve motivation.

Overactivity in the LHb neurons could therefore prove to be an important biomarker or depression patients who are suffering from a lack of motivation. In the future, the biomarker could be used to identify patients who would respond well to a drug that can interfere in the LHb pathway.