Biological Markers for Stress and Depression?

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Biological Markers for Stress and Depression?

Jim Windell

           There’s enough evidence to show that the pandemic caused most of us to feel isolated, often lonely. 

           That alone was a reason for increased stress and anxiety. But if you factor in such things as worry about contracting COVID-19, financial distress, and concerns about the health of loved ones, many people experienced severe stressors. And that combination put a great many people at risk for depression.

            Before the pandemic, between 16 and 20 percent of the U.S. population met the criteria for a major depressive disorder during their lifetimes. Those rates undoubtedly climbed since 2019. According to the Kaiser Family Foundation, during the COVID-19 pandemic about four in 10 adults in the U.S. have reported symptoms of anxiety or depressive disorder – a 400 percent increase since 2019.

           We’ve known for a long time that stress is a major risk factor for depression.

           Michael Treadway, a professor in Emory University's Department of Psychology and Department of Psychiatry and Behavioral Science, says that in many ways depression is a stress-linked disorder. “It's estimated that 80 percent of first-time depressive episodes are preceded by significant, chronic life stress,” Treadway says.

           Treadway is the senior author of a new study that looks at how acute stress and chronic stress affect the brain in depression. Although the link between stress and depression is clearly established, the mechanisms underlying this relationship are not. Previous experiments with rodents have shown an association between the response of glutamate -- the major excitatory neurotransmitter in the mammalian brain – and stress. The role of glutamate in humans with depression, however, has been less clear.

           In this new study, recently published in Nature Communications, the researchers at Emory University used brain imaging to identify differences in the neurotransmitter glutamate within the medial prefrontal cortex before and after study participants underwent stressful tasks. The researchers then followed the participants for four weeks, using a survey protocol to regularly assess how participants rated their expected and experienced outcomes for daily activities.

           The 88 participants in the study included people without a mental health disorder as well as unmedicated patients diagnosed with a major depressive disorder. Participants were surveyed about perceived recent stress in their lives before they underwent experiments using a brain scanning technique known as magnetic resonance spectroscopy. While in the scanner, participants were required to alternate between performing two tasks that served as acute stressors: Putting their hand up to the wrist in ice water and counting down from the number 2,043 by steps of 17 while someone evaluated their accuracy.

           Brain scans before and after the acute stressor measured glutamate in the medial prefrontal cortex, an area of the brain involved with thinking about one's state and forming expectations. Previous research has also found that this brain area is involved in regulating adaptive responses to stress. Participants submitted saliva samples while in the scanner, allowing the researchers to confirm that the tasks elicited a stress response by measuring the amount of the stress hormone cortisol in the sample.

           The results of the study found that in healthy individuals the brain scans revealed that glutamate change in response to stress in the medial prefrontal cortex was predicted by individual levels of recent perceived stress. Healthy participants with lower levels of stress showed increased glutamate in response to acute stress, while healthy participants with higher levels of stress showed a reduced glutamate response to acute stress. This adaptive response was comparatively absent in the patients diagnosed with depression.

           “To our knowledge, this is the first work to show that glutamate in the human medial prefrontal cortex shows an adaptive habituation to a new stressful experience if someone has recently experienced a lot of stress,” commented Treadway. “Importantly, this habituation is significantly altered in patients with depression. We believe this may be one of the first biological signals of its kind to be identified in relation to stress and people who are clinically depressed.”

           The decrease in the glutamate response over time appears to be a signal, or a marker, of a healthy adaptation to stress, according to Treadway. “And if the levels remain high that appears to be a signal for maladaptive responses to stress.”

           “Learning more about how acute stress and chronic stress affect the brain may help in the identification of treatment targets for depression,” adds Jessica Cooper, first author of the study and a post-doctoral fellow in Treadway's Translational Research in Affective Disorders Laboratory. “We were able to show how a neural response to stress is meaningfully related to what people experience in their daily lives,” Cooper says. “We now have a large, rich data set that gives us a tangible lead to build upon as we further investigate how stress contributes to depression.”

           To read the original article, find it with this reference:

Jessica A. Cooper, Makiah R. Nuutinen, Victoria M. Lawlor, Brittany A. M. DeVries, Elyssa M. Barrick, Shabnam Hossein, Daniel J. Cole, Chelsea V. Leonard, Emma C. Hahn, Andrew P. Teer, Grant S. Shields, George M. Slavich, Dost Ongur, J. Eric Jensen, Fei Du, Diego A. Pizzagalli, Michael T. Treadway. Reduced adaptation of glutamatergic stress response is associated with pessimistic expectations in depression. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-23284-9



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