Study: People With Depression May Not Adapt as Well to Stress

Man under stress illustration.

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Key Takeways

  • A new study found that people with major depressive disorder may experience difficulty responding to stress.
  • Participants with depression lacked a biomarker that indicates resilience to chronic stress.
  • Different medications and therapies can help people with the condition better develop their response to stress.

Depression can affect how people respond to and interpret curveballs sent their way. Now scientists at Emory University found that, due to a mechanism in the brain, people with major depressive disorder may not have the tools to be resilient in the face of chronic stress.

The researchers identified a biomarker, or a medical sign, that indicates resilience to chronic stress in the brain. People with major depressive disorder were lacking that marker—which only led to further pessimism in daily life.

Participants were asked to partake in repeated stressors. In people without depression, the marker glutamate spiked in response to stress. People with major depressive disorder lacked a response entirely.

"Despite repeated stressors that suggests to us that perhaps the individual's ability to respond to those stressors, is going to be lower if they are depressed, than if they are not depressed," Melissa Shepard, MD, a psychiatrist based in Baltimore who was not involved in the study, tells Verywell.

The study was published in the Nature Communications journal in late May.

People With Depression Responded Differently to Stress

The study included 88 participants, some of whom had no history of psychiatric disorder and others who were diagnosed with major depressive disorder but were unmedicated.

What Is Major Depressive Disorder?

Major depressive disorder is a common form of depression that causes a persistent feeling of sadness and loss of interest. This mental health disorder does not have one universal cause, but biological differences, brain chemistry, and inherited traits can all play a role.

Participants had to complete tasks that acted as acute stressors, intended to be immediate and intense. They were asked to put one of their hands in ice-cold water and count down from 2,043 by steps of 17.

Before and after these stressors, participants underwent MRIs and had their saliva sampled to measure their levels of glutamate, a neurotransmitter that served as this marker for resiliency.

Participants in the control group put their hands in warm water and could count consecutively, which should be less stressful.

The researchers found that healthy people with lower levels of stress had increased levels of glutamate in response to the stressful situation.

In comparison, healthy people with higher levels of stress experienced reduced levels of glutamate. A glutamate adaptive stress response was largely absent for people with major depressive disorder.

The absence of an adaptive response to stress could also, according to the researchers, lead to "stress-induced anhedonia," which is an inability to enjoy normally pleasurable activities. It's a core clinical feature of depression and other mental conditions.

"In this case, what they were talking about was the ability to feel pleasure and the willingness to seek pleasurable experiences," Aimee Daramus, PsyD, a licensed psychologist based in Chicago, tells Verywell. "So we're talking about these chemicals, mainly affecting the reward pathways, the things that make you feel good when you do something enjoyable."

How Inflammation Can Affect People With Depression

In addition to the near absence of a glutamate adaptive stress response, inflammation can also affect the worldview of people with depression.

While the relationship between depression and inflammation is still being explored, there are some factors associated with depression that increase inflammation.

These include stress, metabolic factors such as obesity and metabolic syndrome, and medical illness and their treatments.

"We know that there are inflammatory markers are increased in people with depression, so it may be that people who are depressed are less able to learn or think about their experiences in a way that is healthy," Shepard says.

How People With Depression Can Better Manage Stress

There are different steps that people can take to better manage their depression. These include medications, therapies, and finding different activities in one's life that bring people joy.


Antidepressants can play a role in helping people with major depressive disorder better manage stress.

A January 2019 systematic review published in the Progress in Neuro-Psychopharmacology and Biological Psychiatry journal evaluated 17 studies on antidepressants to see their effectiveness in managing anhedonia.

The researchers found that most antidepressants were effective in treating symptoms of an inability to feel pleasure in people who live with depression.

"The anti-inflammatory mechanism and some of the neural connectivity that [antidepressants] promote seems like it can help us almost find those more positive things, you know, see things with a little bit less severe of a response to stress," Shepard adds.

However, Shepard notes that it can be a challenge for some patients to find out which antidepressant or combination of antidepressants works best for them.


Therapy can also effective in helping people with depression better manage their stress and other challenges they face that can exacerbate their condition.

Daramus says that cognitive-behavioral therapy (CBT) and dialectical behavior therapy, for example, could help people with mental illness address stressors. Problem-solving is an important part of CBT.

"One part of CBT is learning to see that, 'Yes, it is absolutely 100% true, things are pretty bad for you right now,' but that will not always [be true]," she says. "Trying to find a healthy activity will stimulate your reward pathways...and might not just leave you feeling better at the moment but give you a chance to kind of argue with those thoughts, 'Okay I know I feel bad right now, but I also know that everything isn't bad and won't be bad forever.'"

Daramus also notes that just like medication, people may find different types of therapies and exercises to be more helpful for them than others. For people who live with major depressive disorder, reaching out for help and continuing treatment can be a very difficult but crucial step.

"In therapy, we sometimes have to experiment or create a little bit of a custom mix for exactly what's going to work with somebody," she says. "Depression makes it easy for the person to be just too tired or discouraged to even show up."

What This Means For You

If you live with major depressive disorder or another mental illness, it may be difficult to cope with stress on top of existing mental health issues. It may be helpful to work with a mental health professional to find new ways to better cope with stress. Physical exercise, meditation, and engaging in mindfulness are all steps you can take to cope at home.

3 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Cooper JA, Nuutinen MR, Lawlor VM, et al. Reduced adaptation of glutamatergic stress response is associated with pessimistic expectations in depressionNat Commun. 2021;12(1):3166. doi:10.1038/s41467-021-23284-9

  2. Miller AH. Beyond depression: the expanding role of inflammation in psychiatric disordersWorld Psychiatry. 2020;19(1):108-109. doi:10.1002/wps.20723

  3. Cao B, Zhu J, Zuckerman H, et al. Pharmacological interventions targeting anhedonia in patients with major depressive disorder: a systematic reviewProg Neuropsychopharmacol Biol Psychiatry. 2019;92:109-117. doi:10.1016/j.pnpbp.2019.01.002

By Julia Métraux
Julia Métraux is a health and culture writer specializing in disability.