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Biomarker found that can track depression and antidepressant response

In a new proof of concept study, researchers have identified a biomarker in human platelets that can track depression and reveal the efficacy of antidepressants.


According to the World Health Organization, major depressive disorder (MDD) is the most common cause of disability worldwide. It affects as many as one in ten individuals at any given time. In addition, in the United States, it costs nearly $300 billion per year. While antidepressants provide some benefit, most treatment is not always effective. Approximately one-third of treated individuals do not achieve remission. There are also several adverse events associated with antidepressants that affect compliance. Due to the substantial costs associated with MDD, there is an urgent need to optimise treatment options.

Several previous studies have shown that chronic antidepressant treatment increases physical coupling between the heterotrimeric G protein, Gs-alpha (Gsα), and adenylyl cyclase. Depression is associated with decreased adenylyl cyclase, which is made in response to neurotransmitters such as serotonin and epinephrine.

Mark Rasenick, research lead, explained:

“When you are depressed, adenylyl cyclase is low. The reason adenylyl cyclase is attenuated is that the intermediary protein that allows the neurotransmitter to make the adenylyl cyclase, Gs-alpha, is stuck in a cholesterol-rich matrix of the membrane – a lipid raft - where they don’t work very well.”

A cellular biomarker for depression

In a new study, published in Molecular Psychiatry, researchers assessed the hypothesis that antidepressant treatment changes Gsα enabling it to translocate from the lipid raft to the non-raft region. This translocation was suspected to enable the completion of neurotransmitter action and thereby stimulate adenylyl cyclase.

In total, there were 49 individuals with MDD and 59 healthy controls. The team measured the basal and prostaglandin E1 (PGE1) stimulation of Gsα-adenylyl cyclase to calculate the extent of coupling. MDD subjects had significantly lower PGE1 activation of adenylyl cyclase activity compared to controls.

After this, they investigated 19 MDD individuals who completed a 6-week antidepressant treatment trial. The 11 antidepressant responders were found to have a significant increase in PGE1-stimulated adenylyl cyclase compared to non-responders.

Overall, this study has shown that increased PGE1 stimulated adenylyl cyclase was associated with antidepressant response in MDD subjects. The researchers hypothesise that they will be able to use this blood test to determine if antidepressant therapies are working. A blood test may be able to show whether Gsα was out of the lipid raft as soon as one week after beginning treatment. 

“What we have developed is a test that can not only indicate the presence of depression, but it can also indicate therapeutic response with a single biomarker, and that is something that has not existed to date,” said Rasenick.

Image credit: canva

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Biomarkers / Depression