Novel inflammatory biomarker predicts depression

By Naveed Saleh, MD, MS
Published December 11, 2020

Key Takeaways

Loads of research studies have delved into the causes of depression, with an emerging focus on the role played by inflammation. Either in the absence or presence of comorbid disorders such as diabetes and rheumatoid arthritis, those with depression exhibit higher levels of inflammatory biomarkers.

While previous studies have supported an association between increased levels of high-sensitivity C-reactive protein (hs-CRP) and depression, a recent study published in the Journal of Clinical Psychiatry found a new correlation between depression severity and levels of GlycA, another type of inflammatory biomarker. The researchers suggested the possible clinical utility of GlycA as a novel biomarker for depression. 

“GlycA has a lower intraindividual variability and may serve as a more stable indicator of inflammation compared to hs-CRP,” wrote the authors. “However, to our knowledge, no studies to date have examined the relationship between GlycA and depression.”

Findings

In the current study, researchers mined data from the Dallas Heart Study, a community-based cohort involving 3,033 participants. The team hypothesized that serum GlycA levels would predict scores on the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR). After compensating for various covariates—including age, sex, ethnicity, drinking status, smoking status, antidepressant use, and education level—the researchers found a correlation between GlycA levels and depression symptom severity assessed by QIDS-SR score. They did not, however, find a correlation between hs-CRP levels and depression severity.

A mechanism explaining cause remains to be elucidated, according to the researchers. They noted that previous findings have linked inflammation to biologic and psychologic stressors. Inflammation arises due to proinflammatory cytokines, which facilitate serotonin transport and uptake, thus decreasing the availability of serotonin. No surprise that lower serotonin levels are linked to depression. Those with depression exhibit higher levels of proinflammatory cytokines, possibly due to stress and other psychosocial factors.

Strengths and weaknesses

According to the researchers, the study had a number of strengths. First, the link between GlycA and depressive symptoms was surveyed in a large, multiethnic sample. Second, QIDS-SR is a reliable and valid indicator of depression severity. Third, whereas hs-CRP levels can vary, GlycA levels are more consistent when taken as single readings. Testing for GlycA levels, however, is costlier than testing for hs-CRP levels, which may limit its adoption in clinical settings, according to the authors.

The study also had certain limitations. Its cross-sectional design permitted only the assessment of depressive symptoms at one point in time, without a diagnosis of depression established. In addition, QIDS-SR scores were determined via self-report. Furthermore, cases were drawn from a general population and not those with clinical depression, with average QIDS-SR scores in the sample indicating mild symptoms of depression. Also, blood draws were not taken at a specific time of day, and biomarker values could be subject to diurnal variation. Finally, although the multiethnic nature of the sample could boost generalizability, it could also add variability to the study, thus dialing down the study’s power.

In other findings, the researchers noted that alcohol use was not associated with depression severity, with data gathered on the topic by other researchers mixed. Notably, in the current study, data were based on an evaluation of a general population with limited prevalence of problem drinking. Furthermore, Black participants exhibited fewer depressive symptoms as indicated by QIDS-SR score vs White participants, a finding that is supported by previous research. The researchers also found that the average BMI in the study indicated obesity; obesity is a predictor of depression. Moreover, obesity can heighten GlycA levels, according to findings from previous research on the topic. 

Next steps

The authors viewed their study as a first step. Looking forward, they wrote that “future studies should assess this relationship longitudinally, comparing healthy and depressed populations to determine differences in inflammation levels.” In addition, they noted, studies to determine whether GlycA predicts antidepressant response—as hs-CRP does—are needed. 

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