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Diagnosis of depression can be boosted by the discovery of new biomarkers

 


Having a simple biochemical marker of depression is essential for diagnosing the disease and for tracking the effectiveness of drug therapy in the treatment of the neurochemical aspects of the disorder. Therefore, researchers at the University of Illinois at Chicago (UIC) have released data from a new study that identifies biomarkers for human platelets that track the degree of depression.

Some studies have shown in human and animal models that depression is consistent with a decrease in adenylate cyclase, a small intracellular molecule produced in response to neurotransmitters such as serotonin and epinephrine. Based on previous research by researchers in.

“When you are depressed, adenylate cyclase is low. The reason that adenylate cyclase is attenuated is because of the intermediate protein Gs alpha (Gsα) that allows neurotransmitters to make adenylate cyclase. Well, because the lipid raft membrane cholesterol is packed in a rich matrix, ”explained Dr. Mark Lasenic, senior researcher and professor of physiology, biophysics, and psychiatry at UIC. ..

Discoveries from new research — recently published Molecular psychiatryNew peripheral biomarkers for depression and antidepressant responses— Identified cellular biomarkers of Gsα translocations from lipid rafts. Biomarkers can be identified by a blood test.

“We have developed a test that can not only show the presence of depression, but also a therapeutic response with a single biomarker, which has never existed before,” he said. Researcher Rasenick said. Career Scientist at Jesse Brown VA Medical Center.

The researchers hypothesized that perhaps one week after the start of treatment, this blood test could be used to determine if antidepressant therapy was working. Previous studies have shown that Gsalpha was out of the lipid raft when patients showed improvement in their symptoms of depression. However, in patients who took antidepressants but did not improve their symptoms, Gsalpha was still clogged in the raft, so adding antidepressants to the bloodstream was not enough to improve their symptoms. was.

“This small proof-of-concept study tested the hypothesis that the translocation of Gsα from lipid rafts to easier activation of adenylate cyclase is a biomarker of the clinical response to antidepressants,” the authors said. I am writing. “At the time of the screening visit, there were 49 subjects with MDD (HamD17 score of 15 or higher) and 59 healthy subjects. The AlphaScreen assay was used to assess the degree of coupling between Gsα and adenylyl cyclase. Both basal activity of adenylyl cyclase and prostaglandin E1 (PGE1) stimulation were measured. On the screen, platelet samples obtained from MDD subjects had significantly more PGE1 activation of adenylate cyclase activity than controls. It was revealed to be low (p = 0.02).

The authors went on to say, “Since then, 19 consented MDD subjects completed a 6-week open-label antidepressant treatment trial. 11 antidepressant responders (more than 50% improvement in HamD17 from the screen) , PGE1-stimulated adenylate cyclase showed a significant increase compared to non-responders (p = 0.05), and the effect of PGE1 / Gsα lipid raft biomarker was 0.83. PGE1 stimulation was 8 responders (72.7). %) And 2 non-responders (25.0%) increased by more than 30% from the screen rating. [Fisher exact = 0.07] With a positive prediction of 80.0% response. In this small pilot study, PGE1-stimulated increases in adenylate cyclase were associated with antidepressant responses in MDD subjects.

A blood test may show if Gs alpha has left the lipid raft after a week.

“Platelets turn over in a week, so there are changes in people who get better, so we can see biomarkers that predict successful treatment,” says Rasenick.

Currently, patients and their doctors have to wait weeks, sometimes months, to determine if antidepressants are working, and if so, try different treatments. Will be done.

“About 30% of people don’t get better — their depression doesn’t go away. Perhaps failure causes failure, assuming that both the doctor and the patient do nothing,” Rasenick concludes. rice field. “Most depression is diagnosed in the clinic of an unscreened family doctor. With this test, the doctor can say, so this may need to be revisited. Hmm.”

Sources

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2/ https://www.genengnews.com/topics/translational-medicine/biomarkers/depression-diagnostics-could-get-boost-with-discovery-of-new-biomarker/

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