Impaired sleep quality may help explain the long-term effects of depressive symptoms on inflammation

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New research published in PLOS One suggests that depressive symptoms are longitudinally associated with increased inflammation. Furthermore, the new study provides evidence that sleep quality plays a significant role in the link between depressive symptoms and later inflammation.

“I became interested in the long-term health impact of depressive symptoms from my personal experiences in mild depressive symptoms,” explained study author Sunmi Song, a research professor at the Department of Health Sciences of Korea University. “I felt that I have lost my usual high energy and motivation after the symptom relief. I had wondered how far the lingering impact may last, and luckily, I had the chance to study this using the Midlife in the United States (MIDUS) cohort data, in which my colleagues and I examined the impact of depressive symptoms on systemic inflammation in the body at 11-year follow-up.”

The MIDUS study assessed the depressive symptoms of 7,108 midlife adults in 1995. Eleven years later, 968 of these participants stayed overnight at a research center. In the morning, they completed an assessment of sleep quality and provided fasting blood samples, which were used to measure interleukin-6 (IL-6) and C-reactive protein (CRP).

IL-6 and CRP are inflammatory biomarkers that have been associated with a variety of inflammatory diseases. IL-6 is a cytokine that is produced by various cell types, including monocytes, macrophages, and T cells. CRP is a protein that is produced in the liver in response to inflammation. Both IL-6 and CRP are involved in the inflammatory response and have been linked to diseases such as arthritis, inflammatory bowel disease, and psoriasis.

The researchers found that greater depressive symptoms were associated with higher levels of CRP in both men and women, and higher levels of IL-6 in women (but not men). “In the present sample, for the main effect of depressive symptoms on CRP, each additional depressive symptom was associated with a 1.25 mg/L higher levels in CRP for both genders and a 1.40 pg/mL higher levels in IL-6 for women,” the authors explained. “This indicates that the experience of even mild depressive symptoms has the potential to be associated with higher systemic inflammation a decade later.”

The findings held even after controlling for concurrent depressive symptoms, age, socio-economic status, race, BMI, smoking, chronic health conditions, and medication use.

“The study findings suggest that the depressive symptoms of you or your loved ones may require a long-term care plan to promote both physical health and psychological well-being. In other words, seeking out psychiatric treatments for the acute depressive symptoms may not be enough for your full recovery,” Song told PsyPost.

In addition, the researchers found evidence that subjective sleep quality mediated the association between depressive symptoms and CRP. Greater depressive symptoms in 1995 were associated with worse overall sleep quality during the clinical stay, which in turn was associated with higher levels of CRP for both men and women.

“Our study also suggests that monitoring your sleep quality may be particularly useful to notice the lingering harmful effect of previous depression on the body as sleep quality explains the longitudinal association between depressive symptoms and inflammation,” Song explained.

“I personally found it helpful to practice physical exercise and expressive writing as a part of a daily routine to maintain good sleep and overall recovery from depressive symptoms,” Song explained. “(There are robust research findings to back up the efficacy of the two methods on depressive symptoms and clinical depression.) If you’d like to know more about how to do expressive writing, I recommend a book ‘Expressive Writing: Words that Heal’ by James Pennebaker and John Evan.”

The findings are in line with a 2020 meta-analysis of 107 cross-sectional studies, which found that inflammatory markers tended to be elevated among depressed patients. But as with any study, the new research includes some limitations.

“The major caveats of the study findings are that those people with depressive symptoms may show elevated inflammation 11 years later because they already had elevated inflammation in the first place,” Song said. “The MIDUS study did not measure the levels of inflammation at baseline (when the study started) but measured it only at 11 years later.”

“Inflammation in the body is known to be associated with current experiences of depressive symptoms. Although we tried to account for that by controlling for those with inflammatory chronic disease conditions such as cardiovascular disease and arthritis at baseline and depressive symptoms at the time of inflammation assessments, future studies are needed to verify if the long-term lingering impact of mild depressive symptoms remain to be present after controlling for baseline levels of inflammation.”

“I’d like to add that depressive symptoms are usually triggered by very difficult and painful life events such as loss of your loved ones, major failure of your life goals, or unresolved social conflicts with important others,” Song said. “We should allow yourself or your loved ones with depression enough time and resources to heal and grow from the experience.”

“My study shows that the healing process may take longer than people usually expect it to take. I hope that people with current or history of depression take this as a chance to grow by digesting the personal meaning of pain and suffering in your life and rebuilding your daily routine healthier. I would like to send lots of love and empathy to those who suffer from lingering negative impacts of depression.”

The study, “The longitudinal connection between depressive symptoms and inflammation: Mediation by sleep quality“, was authored by Sunmi Song, Natasha N. DeMeo, David M. Almeida, Marzieh Majd, Christopher G. Engeland, and Jennifer E. Graham-Engeland.