Can depression cause lasting changes in immune cells?

• Researchers have established a link between depression and alterations in immune cells’ shapes and function for the first time.
• Depression can cause negative physiological changes in the body, including low-grade inflammation and an increased output of certain stress-related hormones.
• A new study has found that raised stress hormones and chronic inflammation observed in long-term depressive conditions can cause cell membranes to bend and become deformed.
• These physiological responses to depression can cause the immune cell membrane to lose its ability to maintain its shape and internal organization, affecting its function and possibly leading to other diseases.

For the first time in history, a new study has established a connection between long-term persistent depressive disorders and mechanical changes in blood cells, and changes in immune cell shape and function.

The study, reported in the journal Translational Psychiatry, was carried out by researchers from the University of Zurich in Switzerland, the Technische Universität Dresden (TU Dresden), the Max Planck Institutes for the Science of Light, and the Max-Planck-Zentrum für Physik und Medizin Erlangen in Germany.

The researchers performed a cross-sectional case-control study using a test that could determine a cell’s ability to change its shape using healthy blood samples based on changes in blood cell images.

Dual focus: biological and psychological therapies  

The lead author of the study Dr. Andreas Walther conducted the research while working as a postdoc to Clemens Kirschbaum, the chair of biopsychology at TU Dresden. Dr. Walther feels it is essential to advance biological and psychological therapies to treat depressive conditions more efficiently and sustainably in the long term.

He explains:

“We are working in parallel on research into pharmacological therapies to improve dysfunctional biology as well as psychological therapies to improve dysfunctional cognitive and emotional processes. Indeed, in my opinion, only a holistic approach can understand and efficiently treat this complex disorder and hopefully prevent much suffering in the future.”

How the study was conducted

The study included 69 pre-screened individuals at high risk for depressive disorders and 70 matched healthy controls. The participants underwent clinical evaluation using a globally recognized clinical interview process for diagnosing mental health conditions, called the Composite International Diagnostic Interview.

An artificial intelligence (AI) method of deep learning scanned over 16 million blood cell images. These images were then classified into main blood cell types and measured using parameters such as cell size, in addition to their ability to change shape and exhibit cell membrane deformability.

The scientists discovered that immune system cells known as monocytes, lymphocytes, and neutrophils were most deformable in patients with a persistent depressive disorder over their lifetime than in control subjects.

Two depression subtypes

A major depressive disorder (MDD) requires a two-week phase to be diagnosed and select specified criteria. Similarly diagnosed, a persistent depressive disorder (PDD) lasts for more than two years and can affect an individual for a lifetime. Depressive disorders are the leading causes of disability worldwide.

Depression causes chronic low-grade inflammation and increases stress hormone production. Both of these effects can potentially interfere with the structure of immune cells by deforming their shape.

It is unclear whether the increase in immune cell deformability that occurs with PDD confers over-or under-activity of the immune system, both states being bad for health outcomes.

Medical News Today spoke to Dr. Jean Kim, a clinical assistant professor of psychiatry at George Washington University, about the study’s findings.

“[The results] postulate that blood cell deformability is a marker of altered immune cell states, although it seems somewhat unclear and variable in which direction (higher or lower) it correlates with immune hyperactivity versus hypoactivity from what they described,” she said.

“Stress hormones like glucocorticoids are thought to increase some white blood cells and indicate inflammation when the [hypothalamus-pituitary-adrenal] axis is activated during anxiety or depression,” she added.

Additional effects on the body

MNT also spoke with Dr. Sheldon Zablow, a child, adolescent, and adult psychiatrist and a voluntary assistant professor of child psychiatry at the UC San Diego School of Medicine.

“Chronic inflammation as well as chronic depression produces a wide variety of chemicals, such as cortisol, which deforms the structure of the white blood cells of immunity,” said Dr. Zablow.

“This [depression-induced] deformability of white blood cells reduces their capacity to fight infection or repair damage and increases the risk of a wide variety of illnesses besides depression…chronic inflammation causes or worsens obesity, heart disease, dementia, diabetes, and autoimmune illnesses.”
— Dr. Sheldon Zablow

A blood test for depression?

Dr. Zablow said that in the future, testing the deformability of blood cells could become standard for people with chronic inflammation or those at increased risk of long-term depression.

Dr. Kim called the findings interesting but said more research was needed to understand the wider implications.

“Although the full clinical meaning and implications of this proxy for immune cell ‘deformability’ remain unclear, [and] what the various results mean, in terms of what stage/severity of depression can do to the immune system and why/how, [has yet to be determined],” she said.

“If further studies continue to replicate these trends and findings, potentially one could even one day develop a blood test to ‘detect’ depression which would be very useful, or at least a way to note risk for inflammation-related conditions and treat patients accordingly.”
— Dr. Jean Kim

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