Biomarker Discoveries Promise Improved Depression Treatment

Markers of inflammation, brain activity, and other factors could point the way to more effective therapies.

Researchers involved in the battle against major depressive disorder (MDD) are focusing increasingly on identifying metabolic markers that could one day help confirm the diagnosis of the mood disorder, indicate appropriate treatments, track treatment outcomes, and perhaps even prevent its development in the first place. The effort aims at improving on the current trial-and-error approach to diagnosing and treating MDD, which affects as many as seven percent of American adults each year.

“If we can see that a patient’s biomarkers are abnormal, that would help us confirm a diagnosis of depression and perhaps help us find the proper treatment sooner, without having to try a series of possible therapies,” says Dr. David Mischoulon, MD, PhD, director of research at MGH’s Depression Clinical and Research Program. “Biomarkers would also help eliminate the shame some people feel about having depression by showing MDD to be a biological disorder that can be diagnosed by a test, identifying it as a medical illness.”

In a recent example of such research, a study of more than 1,800 teenagers in the United Kingdom revealed that boys who reported symptoms of depression and had elevated morning levels of the stress hormone cortisol in their saliva were as much as 14 times more likely to develop major depression within 12 to 36 months than boys who had low levels of cortisol and no depressive symptoms. The study, which was published on Feb. 17, 2014 in the Proceedings of the National Academy of Sciences, may make it easier for medical care providers to identify individuals at high risk for MDD and intervene at an earlier stage.

WHAT YOU CAN DO

If you or a loved one experiences the following symptoms of depression for two weeks or more, seek a professional assessment:

  • Fatigue
  • Restlessness
  • Feelings of sadness and/or guilt
  • Feelings of hopelessness
  • Loss of pleasure in activities previously enjoyed
  • Sleep and appetite disturbances
  • Problems with concentration
  • Thoughts of suicide

MGH researchers, too, have been studying metabolic biomarkers for MDD—in this case, with an eye to improving treatment response. In a paper presented at the American Psychiatric Association’s annual meeting last year, they reported on a study of folic acid therapy in 75 adults with MDD who had failed to respond to selective serotonin reuptake inhibitor (SSRI) antidepressant medications. Their investigation revealed that obese participants and/or those with elevated blood levels of an inflammatory protein called high-sensitivity C-reactive protein were much more likely to respond to their antidepressant medication when they took a form of folic acid called L-methylfolate along with it.

“This suggests that among people with MDD, there may be individuals with inflammatory activity in their systems that may contribute to their depression,” says Dr. Mischoulon, a co-investigator in the study. “If biomarkers such as these were to allow us to identify beforehand patients more likely to respond to a particular treatment, that could help us avoid weeks, months or even years of failed trials of other types of medications or therapy. Once this work is replicated, I think it will allow clinicians to make prescribing decisions with greater confidence.”

Other markers

Other notable studies among the growing number of research efforts looking for good diagnostic and prognostic MDD markers include:

  • Research that suggests that using brain scans to measure activity patterns in a region of the brain’s cortex called the insula can be used to predict which patients would be more likely to achieve remission from their MDD symptoms through psychotherapy, and which patients would respond better to antidepressant medication. The research was published in the June 12, 2013 issue of JAMA Psychiatry.
  • A review of multiple research studies into MDD biomarkers published in the Jan. 1, 2014 issue of Progress in Neuro-Psychopharmacology and Biological Psychiatrythat suggests that markers of inflammation and oxidative stress offer potential for helping with diagnosis, predicting treatment response, and preventing the onset or relapse of MDD.

Promise for the future

“These new technologies are promising, but more data will be required before the findings can be translated into widespread application in clinical settings,” Dr. Mischoulon cautions. “And they won’t be a cure-all. We still have to develop treatments that work better. The good news is that biomarkers can help us in that process, too, by allowing us to more closely track the efficacy of new medications.”

See What You Can Do for symptoms of major depressive disorder.

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