Inflammation Fans Flames of Depressive Symptoms

Megan Brooks

November 20, 2015

A new study supports a link between inflammation and depression and adds to the literature by associating inflammation with specific symptoms of depression, including sleep troubles and lack of energy and appetite.

Individuals with depression are known to have elevated levels of inflammatory markers, such as C-reactive protein (CRP), and it has recently been suggested that this association may be symptom specific, Markus Jokela, PhD, from the University of Helsinki, Finland, and colleagues note in a research letter published online November 18 in JAMA Psychiatry.

"Higher levels of inflammation are particularly likely to underlie depression symptoms that characterize sickness behavior, including fatigue, reduced appetite, withdrawal, and inhibited motivation. From an evolutionary perspective, such symptoms have the beneficial effect of preserving energy resources for use in fighting infection and promoting healing processes," they say

Dr Jokela and colleagues tested the hypothesis that the association between CRP and depression is symptom-specific using data on roughly 15,000 men and women who participated in three US National Health and Nutrition Surveys. The mean age of the participants was 47.5 years, and the median CRP level was 2 mg/L (interquartile range, 0.8 - 4.7 mg/L).

"Inflammation was associated with a range of depression symptoms, particularly with tiredness, lack of energy, sleep problems, and changes in appetite," the investigators report. These symptoms characterize sickness behaviors seen in people who are physically ill.


Symptom Adjusted OR (95% CI)
Sleep problems 1.14 (1.07 - 1.21)
Tiredness, lack of energy 1.22 (1.15 - 1.30)
Changes in appetite 1.17 (1.09 - 1.27)

OR, odds ratio; CI, confidence interval.


When CRP was categorized into quartiles, independent dose-response patterns emerged for sleeping problems (OR, 1.29, 1.33, and 1.51 for the second, third, and fourth CRP quartiles, respectively, compared with the first quartile; P < .001), tiredness or lack of energy (OR, 1.02, 1.32, and 1.68 for the second, third, and fourth quartiles, respectively; P < .001), and appetite changes (OR, 1.18, 1.23, and 1.65 for the second, third, and fourth quartiles, respectively; P < .001).

Inflammation was also associated with cognitive and emotional symptoms of depression, including anhedonia, depressed mood, feelings of self-worth, concentration, and suicidal ideation, although these associations were not independent of the other depression symptoms.

"Further research is needed to determine whether changes in inflammation predict changes in specific symptoms and to identify metabolic pathways that mediate such changes," Dr Jokela and colleagues conclude.

Role for Anti-inflammatory Agents?

Reached for comment, Golam Khandaker, MBBS, MPhil, MRCPsych, PhD, clinical lecturer, Department of Psychiatry, University of Cambridge, United Kingdom, told Medscape Medical News that "while the association between inflammatory markers such as CRP and depression is well known, studies such as this looking at particular symptoms provide important clues for mechanism of illness pathogenesis.

"This work points to a potentially important role for inflammation in the pathogenesis of the so-called somatic symptoms of depression, such as sleep problems, anergia, and loss of appetite, which are, of course, an integral part of the syndrome of depression," Dr Khandaker said.

The findings, he added, "may help to identify patients who would benefit from immunotherapy. It may be tempting to speculate from the results that anti-inflammatory drugs would be helpful for patients with predominantly somatic rather than psychological symptoms of depression. However, there is a need to carry out RCTs [randomized controlled trials] of anti-inflammatory drugs in depression to test this assumption."

As previously reported by Medscape Medical News, a recent meta-analysis of 14 relevant randomized, placebo-controlled studies found that nonsteroidal anti-inflammatory drugs (NSAIDs) may help ease depressive symptoms.

Results showed that the adjunctive use of NSAIDs was associated with improved antidepressant treatment response without an increased risk for adverse effects. In particular, add-on treatment with celecoxib (Celebrex, Pfizer Inc) improved antidepressant effects, remission, and response.

The study had no commercial funding. The authors report no relevant financial relationships.

JAMA Psychiatry. Published online November 18, 2015. Abstract


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