Two Endocannabinoid-Related Genes Were Identified as Potential Biomarkers for Depression | Research

The takeaway

Using machine learning on gene expression data, researchers identified two mitochondrial genes (MRPS11 and SHMT2) — connected to the endocannabinoid system — as significantly reduced in major depression patients, with validated potential as diagnostic biomarkers.

Psychiatry researchers, genomic medicine specialists, and those interested in the molecular basis of the endocannabinoid-depression connection.

What the researchers found

MRPS11 and SHMT2 were identified as significant biomarkers for major depressive disorder, both showing markedly reduced expression in patient samples compared to controls. The findings were validated by RT-qPCR analysis. A biomarker-based nomogram successfully predicted MDD risk. Both genes were co-enriched in the ribosome pathway.

Why it matters

Depression diagnosis currently relies on subjective symptoms. If endocannabinoid system-related gene biomarkers can objectively predict depression risk, it could transform diagnosis and connect the growing understanding of the ECS-mood relationship to clinical practice.

The numbers in context

Two key biomarkers: MRPS11 and SHMT2. Both reduced in MDD. Four differential immune cell types found. Five key miRNAs identified targeting these biomarkers. 31 lncRNAs and 10 transcription factors in regulatory networks. 15 drugs targeting MRPS11, 56 targeting SHMT2.

How the study worked

Analysis of two gene expression datasets (GSE52790 and GSE38206). Weighted gene co-expression network analysis (WGCNA) and machine learning integrated with endocannabinoid system-related genes to identify biomarkers. ROC analysis validated diagnostic performance. RT-qPCR confirmed expression differences. Immune cell analysis, regulatory networks, and drug targeting were also performed.

What this study cannot tell us

Bioinformatics-driven study relying on public datasets. RT-qPCR validation performed but in small samples. MRPS11 and SHMT2 are mitochondrial genes connected to ECS but not core ECS components. No functional validation of the biomarker-disease relationship. Cannot confirm causation.

How to read the evidence

Bioinformatic analysis with RT-qPCR validation, providing hypothesis-generating biomarker candidates but requiring functional and large-scale clinical validation.

When this study was published

Published 2025.

The bigger picture

Linking endocannabinoid system genes to depression biomarkers provides molecular evidence for the ECS-mood connection that clinical observations have long suggested. The drug targeting analysis (71 potential drugs) could accelerate development of ECS-based antidepressant therapies.

Questions still open

How do mitochondrial ribosomal genes connect mechanistically to endocannabinoid signaling? Would these biomarkers perform well in diverse populations? Could cannabinoid-based treatments restore MRPS11 and SHMT2 expression in depression?

Common questions

Does this mean the endocannabinoid system causes depression?

The study found endocannabinoid system-related genes are altered in depression, but this doesn't prove causation. It adds to growing evidence that the ECS plays a role in mood regulation and could be a therapeutic target.

Could a blood test diagnose depression using these biomarkers?

This is an early step. The biomarkers showed good predictive performance in the study datasets, but extensive validation in larger, diverse populations would be needed before any clinical diagnostic test could be developed.

Read the original research

Identification and experimental validation of biomarkers associated with the endocannabinoid system in major depressive disorder.

Hereditas, 162(1), 191

View on PubMed ↗Publisher’s paper ↗

Citation

Wang, Linlin; Chen, Min; Li, Xujuan; Li, Yufeng. (2025). Identification and experimental validation of biomarkers associated with the endocannabinoid system in major depressive disorder.. Hereditas, 162(1), 191. https://doi.org/10.1186/s41065-025-00558-6