An elevated neutrophil-to-lymphocyte ratio (NLR) is significantly associated with increased risk of depressive disorder (DD) and may also correlate with suicide risk among individuals with DD, according to a systematic review and meta-analysis published in the November issue of Harvard Review of Psychiatry, part of the Lippincott portfolio from Wolters Kluwer.

“Studies demonstrate altered immune responses in DD, including diminished lymphocyte reactivity and dysregulated neutrophil activity,” explain Yongjun Chen, MD, of Shandong University of Traditional Chinese Medicine in Jinan, China, and colleagues. “NLR, derived from a routine complete blood count, has emerged as a cost-effective and accessible peripheral biomarker of systemic inflammation.” Theirs is the first comprehensive meta-analysis to investigate both the predictive and prognostic implications of NLR in patients with DD.

A broad, methodologically rigorous review of the evidence

Dr. Chen’s group searched PubMed, Embase, the Cochrane Library, and Web of Science from inception to September 4, 2024. Studies were eligible if they involved patients with primary or secondary depression (any subtype of DD) and reported original data on the association of DD with NLR with sufficient methodological detail.

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The researchers included 37 studies, all published in English between 2015 and 2024, that collectively involved 88,019 participants. Three studies reported only categorical NLR data, 27 reported only continuous NLR data, and seven reported both. Twenty-seven studies derived from Asia, seven from Europe, and three from the Americas. Six were cohort studies and 31 had a case–control design. Participants ranged from 13 to 83 years old and sample sizes ranged from 32 to 34,324.

Using the Newcastle–Ottawa Scale, the research group assessed study quality in three domains: participant selection, comparability of study groups, and outcome ascertainment. In this system, the highest possible score is nine stars. All included studies scored seven or eight stars.

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NLR was related to both DD prevalence and suicide risk

The researchers conducted separate analyses of categorical and continuous variables:

Categorical variables

• Based on 10 studies—Individuals with elevated NLR had a 57% higher risk of developing DD than those with lower NLR (odds ratio, 1.57; 95% CI, 1.28–1.93), with substantial heterogeneity of results (I²=85%; P<0.0001)
• Based on 2 studies—Patients with DD who had elevated NLR were at 56% higher risk of suicide than those with lower NLR (odds ratio, 1.56; 95% CI, 1.26–1.94), with no significant heterogeneity (I²=0%; P<0.0001)

Continuous variables

• Based on 33 studies—NLR was significantly elevated in patients with DD compared to individuals without DD (standard mean difference, 0.73; 95% CI, 0.51–0.94), with substantial heterogeneity (I²=96%; P<0.00001)
• Based on 13 studies—Patients with DD who were considered at risk of suicide had significantly higher NLR than their counterparts who were not considered at risk (standard mean difference, 0.42; 95% CI, 0.23–0.61), with moderate heterogeneity (I²=66%; P<0.0001)

A sensitivity analysis demonstrated that no individual study had undue effect on the overall findings.

“These findings underscore the clinical relevance of systemic inflammation in DD pathophysiology,” Dr. Chen’s group concludes, “and highlight NLR as a cost-effective, accessible tool to inform risk stratification and tailored treatment strategies in psychiatric care.”

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