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Biomarkers – a revolutionary approach to diagnosing and treating depression 

What is a “biomarker?” Generally speaking, these are biological characteristics that can be measured in the human body. When measured in the clinic or lab, biomarkers can signal the presence of a disease or the risk of developing one. They can help health care professionals assess the likelihood that an illness will respond to a specific treatment, monitor disease progression or treatment success, or predict long-term outcomes.

Common examples of biomarkers include:

  • blood pressure readings, which can assess how well heart disease is being controlled
  • gene variations that can indicate an individual’s risk of developing certain cancers
  • A1C, a form of hemoglobin that can be used to help diagnose diabetes

Biomarkers can be used alone or together in a “panel,” “fingerprint,” or “biosignature.” Biomarkers can help classify disease into more meaningful categories, and they can allow more rapid and accurate diagnosis and appropriate treatment of various conditions.

While hundreds of biomarkers for various chronic diseases have been identified and are being used to guide clinical decisions, very few have been validated for mental illnesses. As a result, people living with depression and bipolar disorder must often “try out” several treatments before finding one that’s right for them, and, sadly, far too many feel little to no improvement after enduring years of this trial-and-error approach.

With the aim of finding new tools that can help improve decision-making about diagnosis and treatment to better meet each patient’s unique characteristics, several studies at the U-M Depression Center are examining numerous potential biomarkers that offer the greatest promise for improving the detection, evaluation, and treatment of depression and related illnesses.

Srijan Sen, M.D., Ph.D., is leading a study observing newly minted physicians across 10 different academic medical institutions during the course of their internship year, a time when rates of stress and depression have been shown to increase dramatically.

Dr. Sen’s analysis will assess whether various biomarkers change with chronic stress (in the case of medical internship, stress brought about by long work hours, sleep deprivation, extreme pressure, etc.), and whether these biomarkers may be used to predict the onset of depressive symptoms.  One aim is to identify potential biomarkers that might predict differences in outcomes and suggest opportunities for intervention.

Biomarkers of particular interest in Dr. Sen’s study include cortisol (a stress hormone) as measured through hair samples, a unique measure of cumulative stress, and various inflammatory and cardiovascular factors assessed through blood samples. The hair cortisol component is funded through the Oscar Stern Award at the Depression Center.

Another major part of this project involves continuing to build a bank of DNA samples contributed by the interns that can be analyzed for genetic factors potentially related to depression; in the long term, combining this genetic information with data available on various biomarkers could provide powerful biological profiles of depression risk for individuals.

Julie Kaplow, Ph.D., conducts research to better understand how kids cope after the loss of a parent. One of her studies, the CIRCLE (Coping In Response to Childhood Loss Experiences) Project, is attempting to identify various biological, psychological, and environmental factors that may put these children at greater risk for “maladaptive” grief and future mental health problems, as well as factors that may help promote resilience in the aftermath of parental loss. Maladaptive grief can involve intense feelings of separation distress (really missing the person), identity-related distress (feeling like a part of you died with the person), and preoccupation with the circumstances of the death (upsetting thoughts or images of the way the person died).

Over the course of a year, the study follows children ages 3-12 who have recently lost a parent. As part of this research, Dr. Kaplow will look at various potential biomarkers, including cortisol from saliva and hair samples, measures of inflammation, and heart rate variability, to determine whether these or a host of other measures may help predict a grieving child’s risk of maladaptive grief, post-traumatic stress, depression, anxiety, or other related outcomes.

This could potentially help target interventions toward bereaved children more precisely by helping to identify those at greatest risk at the outset of the grieving process.  This research is also timely in that the DSM-V (the newly revised Diagnostic and Statistical Manual of Mental Disorders) will contain a Persistent Complex Bereavement Disorder, and Dr. Kaplow’s work will shed light on biomarkers that may serve as risk factors or mediating mechanisms for the development of this disorder.

This work has been funded in part by the Todd Ouida Clinical Scholars Award, the Rachel Upjohn Scholars Award, and the Lynn Wilson Memorial Fund. For more information about the study, contact Amanda Burnside at

Rich Dopp, M.D., investigates exercise and its impact on adolescents with depression. In 2008, he began The READY Project (Research on Exercise And Depression in Youth) to see if it would be possible to get adolescents with depression to exercise and stick with a routine. The study required teens to exercise three times per week for 12 weeks. All participants who took on the “assignment” successfully completed it, and their depression levels dropped significantly.

Based on the success of this first study, Dr. Dopp launched a randomized controlled trial (RCT) to help understand how exercise apparently reduces depression in teens. He examined blood samples from participants to examine biomarkers that could indicate changes that exercise might bring about, including measures of brain function, inflammation, insulin resistance, cholesterol, and appetite regulation. As with many early studies, support came from many generous sources;  Depression Center funding included the Rachel Upjohn Clinical Scholars Award, the Todd Ouida Clinical Scholars Award, and even a Depression Center Community Volunteer Committee Mini-Grant.

The GREAT Project (Groups Receiving Exercise As Treatment), Dr. Dopp’s latest study, is a group exercise intervention for teens with either unipolar or bipolar depression. GREAT will study some of the same biomarkers in the blood as the RCT, as well as cortisol as measured in hair samples. One of the objectives of this research is to examine which biomarkers are involved with depression severity levels, how those levels change with exercise, and whether certain biomarkers are predictive of the course of depression. Understanding the interaction of depression with physiological and neurological functioning could help improve how this illness is diagnosed and treated. The Depression Center has continued to help fund Dr. Dopp’s research program with the Feldman Award, a new Rachel Upjohn Clinical Scholars Award, and a gift from Julie Sander.

These are just some examples of the growing body of research intent on pursuing depression biomarkers. Although each of the three projects described here is examining different populations and outcomes, the investigators plan to confer with each other as their studies progress to compare notes on common findings and help improve their analyses. While depression “biosignatures” remain a work in progress, they represent a revolutionary approach for personalized depression diagnosis and treatment.