MicroRNA “Fingerprints” in the Blood May Offer Clues to Bipolar Disorder Biology


By Joao L. de Quevedo, MD, PhD, Director, UTHealth Houston Center for Interventional Psychiatry
November 17, 2025

A New Window into the Bipolar Brain

Bipolar disorder (BD) affects more than 40 million people worldwide, yet its biological underpinnings remain incompletely understood. A new study led by researchers at UTHealth Houston and published in Epigenomics identifies distinctive microRNA (miRNA) patterns in the blood that may reflect molecular changes occurring in the brain.

These tiny RNA molecules regulate gene activity—turning genes “on” or “off”—and have emerged as promising biomarkers for neuropsychiatric disorders. The study focused on extracellular vesicles (EVs), microscopic particles released by cells that can be detected in blood.

Some EVs carry proteins like L1CAM, which is thought to originate from neurons, offering a non-invasive glimpse into the brain’s molecular landscape.

What the Study Found

Researchers analyzed two independent samples of individuals with bipolar disorder and healthy controls:

  • L1CAM-enriched EVs (from presumed neuronal origin)
  • Bulk EVs (from all cell types)

Using RNA sequencing, they identified:

  • 34 miRNAs differentially expressed in L1CAM EVs, including miR-486-5p, miR-128-3p, and miR-301a-3p.
  • 10 miRNAs differentially expressed in bulk EVs.
    Only one miRNA (miR-1-3p) showed consistent changes across both groups.

Notably, several neuron-linked miRNAs were associated with genes such as PTEN and BDNF, both of which are crucial for neural plasticity and have been previously implicated in mood regulation and the pathology of bipolar disorder.

Why It Matters

The study supports the idea that blood-based vesicles may carry molecular “fingerprints” of brain function, potentially serving as biomarkers for bipolar disorder.

Findings from the L1CAM vesicles—those enriched in neuronal material—showed stronger links to clinical features, such as the number of manic episodes and age at treatment onset, suggesting that these signals could help track disease severity or progression.

The team also noted intriguing connections between bipolar disorder and metabolic pathways, including insulin signaling—adding to growing evidence that mood and metabolism share overlapping biology.

The Road Ahead

While preliminary, this work opens the door to liquid biopsy approaches in psychiatry—using blood tests to study brain biology. Future studies with larger, well-characterized cohorts will be crucial to confirm these findings and explore how miRNAs might guide diagnosis or personalized treatment strategies.

Reference
Fries GR, Mirza S, Wang J, Lima CNC, Zhang W, Carbajal Tamez M, Scaini G, Soares JC, Quevedo J. Differential microRNA profiling of blood L1CAM and bulk extracellular vesicles in bipolar disorder. Epigenomics. 2025; 17(1):1-15. doi:10.1080/17501911.2025.2583894

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Disclaimer
This article was created with the help of artificial intelligence (AI) to enhance clarity and readability. All medical and scientific content has been reviewed and approved by Joao L. de Quevedo, MD, PhD, Director of the UTHealth Houston Center for Interventional Psychiatry. This information is intended for educational purposes only and should not be used as a substitute for professional medical advice.