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Elevated peripheral blood Neuron-specific enolase levels correlate with increased risk of MDD and PSDBlood Protein Levels Linked to Risk of Major Depression

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Key Takeaway
Note that elevated peripheral blood NSE levels are associated with increased risk of MDD and PSD.

This meta-analysis synthesized 18 studies to evaluate the relationship between peripheral blood Neuron-specific enolase (NSE) levels and the risk of Major Depressive Disorder (MDD) and Poststroke Depression (PSD). The analysis found that abnormally elevated levels of NSE are closely related to the risk of occurrence for both MDD and PSD. Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was identified.

The authors note several limitations regarding the current evidence base. Specifically, the clinical translational value of NSE as a biomarker requires further validation, and its applicability to other subtypes of depression is not yet established. There is also a noted need for clinical studies involving larger participant numbers to strengthen the evidence.

Clinically, these findings suggest that NSE levels may serve as a biomarker for monitoring and early warning of depression. However, the association does not establish direct causality, and NSE should not be considered a definitive diagnostic tool at this time.

How this fits prior evidence

This meta-analysis addresses a gap in identifying biological markers for mood disorders. While prior coverage has focused on behavioral interventions like assertive case management to reduce suicidal thoughts and pharmacological options such as intravenous ketamine for acute Major Depressive Episode, this finding explores NSE as a potential biomarker for monitoring and early warning of MDD and PSD.

A review of 18 different studies looked at how certain proteins in the blood relate to mental health. Researchers focused on a specific protein called Neuron-specific enolase, often called NSE. They found that people with Major Depressive Disorder and Poststroke Depression often have abnormally high levels of this protein in their blood.

The study suggests that these elevated levels are closely linked to the risk of developing these types of depression. Because the link is consistent across different studies, it may help doctors identify those at risk earlier. However, the researchers noted that more large-scale clinical studies are needed to confirm how this can be used in everyday medical practice.

It is important to remember that while a link was found, the study does not prove that the protein causes depression. Also, the findings may not apply to every type of depression. This research is currently intended as a potential tool for monitoring and early warning rather than a final diagnostic test.

What this means for you:
Higher levels of the NSE protein in blood are linked to an increased risk of major and poststroke depression.

Common questions

What is the role of NSE in depression?

NSE, or Neuron-specific enolase, is a protein found in the blood. This study found that abnormally high levels of this protein are closely linked to the risk of developing Major Depressive Disorder and Poststroke Depression. It may serve as a way for doctors to monitor patients or provide an early warning sign.

Can NSE be used to diagnose depression?

While the study shows a strong link between high NSE levels and depression, it is not yet a definitive diagnostic tool. More research and larger clinical studies are needed to determine how doctors can use this finding to treat patients with different types of depression.

Does high NSE cause depression?

The study shows a link between elevated NSE levels and the risk of depression, but it does not prove that the protein causes the condition. Because the research is still in the early stages of clinical translation, you should speak with a doctor about your specific symptoms.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedJan 2026
View Original Abstract ↓
PURPOSE: Neuron-specific enolase (NSE) is a type of glycolytic enzyme enolase. As NSE is predominantly localized in endocrine cells and neurons, it is frequently recognized as a specific biomarker for peripheral neuroendocrine cells and neurons. Recently, numerous clinical studies have investigated the correlation between peripheral blood NSE levels and depression; however, the findings remain inconsistent. The objective of this study is to systematically evaluate peripheral blood NSE levels in patients with various types of depression. METHODS: We conducted an extensive literature review using various databases such as PubMed, Embase, Cochrane Library, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI). A random-effects model was utilized to compute the pooled effect size (ES) (Hedges' ). Sensitivity analysis, assessment of publication bias, and subgroup analysis were conducted using Comprehensive Meta-Analysis software version 3.0 (CMA 3.0) software. RESULTS: A total of 1175 records were screened for initial eligibility, and 18 reports reported in 18 studies that met the inclusion criteria were included in the meta-analysis. The primary analysis revealed that abnormally elevated levels of NSE in peripheral blood are closely related to the risk of occurrence of major depressive disorder (MDD) or poststroke depression (PSD). Analysis results from different groups on MDD or PSD showed similar outcomes. Sensitivity analysis confirmed the robustness of our findings. The findings on publication bias suggested that this study did not exhibit any significant publication bias. CONCLUSIONS: The findings of our study suggest that abnormally elevated NSE levels in peripheral blood are closely related to the risk of depression, especially MDD and PSD. These findings offer valuable references for the monitoring and early warning of depression. However, the applicability to other subtypes of depression and the clinical translational value requires further validation. In the future, clinical studies with more participants are necessary.
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