- A new study zeroes in on a quick, objective way to diagnose depression and measure the effectiveness of antidepressants for individuals.
- It involves the identification of a biomarker that corresponds to the presence or absence of depression.
- The discovery has to do with the trapping of a key protein inside lipid rafts that typically occurs when a person has depression.
A biomarker, short for “biological marker,” is an objectively measurable biological characteristic that can be associated with a medical condition. A reliable biomarker can be invaluable when a disease presents with no externally measurable objective symptoms.
A new study has identified a biomarker for depression that could help physicians diagnose the condition and assess the effectiveness of antidepressants.
The study’s authors write:
“Given the substantial medical, economic, and social costs involved with MDD [major depressive disorder], there is a clear need for a practical and quantitative method to differentiate and optimize treatment options as early as possible.”
Dr. Mark Rasenick, a distinguished professor of physiology, biophysics, and psychiatry at the University of Illinois Chicago, led the research. Dr. Rasenick told Micro B Life:
“The important thing is that our preliminary results have identified a ‘fellow traveler’ for depression and antidepressant response that is adaptable to high throughput screening.” He noted: “A biomarker need not be part of the disease mechanism of etiology. In fact, in the case of depression, there may be more than one.”
Dr. Dean Frederick MacKinnon, who is an associate professor of psychiatry and behavioral sciences at Johns Hopkins and was not involved in this study, described to MBL his reaction to the study:
“I thought, that’s the holy grail: to find some biological mechanism for depression. Ultimately, the important thing is if they can find anything that helps to explain depression at a biological level because right now, we have very little to go with.”
The study appears in the journal
The value of a depression biomarker
The biomarker might allow a physician to diagnose depression. However, “If somebody comes in the office,” said Dr. MacKinnon, “they have depression, they’re suffering, or they’re struggling to function, and they need treatment,” regardless of what the biomarker indicates.
The biomarker’s main value is its promise of a simple, objective, fast, and accurate test for the diagnosis of MDD and the prediction of treatment response.
For approximately 30% of people who receive a prescription for antidepressants, this treatment proves ineffective. In addition, in successful cases, it may be months before the individual perceives any benefits.
Say the study authors, “the adverse events associated with antidepressants may occur early in the treatment course and contribute to medication noncompliance before the drugs have had a chance to achieve clinical efficacy.”
Dr. Rasenick’s company, Pax Neuroscience, is developing a biomarker test for its MoodMark test suite. Dr. Rasenick described it as “a simple, inexpensive tool that can help diagnose depression and predict — perhaps, given the 7-day life cycle of a platelet, within a week — antidepressant response far before the 2 months required currently.”
The depression biomarker
Previous research has demonstrated that when a person has depression, the activated amount of an enzyme called adenylyl cyclase is lower than usual. This causes a reduction in
Usually, adenylyl cyclase produces cAMP through its interaction with a heterotrimeric protein known as Gs alpha. However, if Gs alpha becomes trapped inside a “lipid raft,” it is unable to interact adequately with adenylyl cyclase. A lipid raft is a cholesterol-rich microdomain within platelets.
“Several studies,” said Dr. Rasenick, “have shown that cAMP is reduced in depressed humans and that antidepressant treatment results in a sustained increase in cAMP production through adenylyl cyclase.”
This suggests that when an antidepressant is successful, it releases Gs alpha from lipid rafts so that it can interact effectively with adenylyl cyclase. When an antidepressant does not work, some amount of Gs alpha remains trapped.
When a person’s blood test reveals that cAMP — the biomarker — has returned to normal levels, it is likely that their treatment is successfully addressing their depression.
Dr. Rasenick noted:
“Our preclinical data show that a large number of antidepressants (about 20) in all classes, as well as some atypical compounds, increase mobility of Gs alpha.”
“Cause and effect?” asked Dr. Rasenick. “We need a lot more data in order to answer that.”
Nonetheless, a more immediate means of assessing the value of an antidepressant for an individual is welcome. Said Dr. MacKinnon, “If this proves to be useful in helping us to refine better drugs that have fewer side effects because they go right to this system, that would be a real plus.”