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Related Experiment Video

Updated: May 5, 2026

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Intron Retention as a Homeostatic State Variable for Drug Response and Recovery: Lessons from Depression for Broader

Norihiro Okada1, Kenshiro Oshima1, Akiko Maruko1

  • 1School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan.

International Journal of Molecular Sciences
|May 4, 2026
PubMed
Summary
This summary is machine-generated.

Intron retention (IR) offers a promising molecular biomarker for depression, reflecting stress adaptation and treatment response. This upstream regulatory mechanism can outperform gene expression markers for monitoring patient recovery and drug efficacy.

Keywords:
depressiondrug responsehomeostasisinflammationintron retentionmild cognitive impairmentpharmacodynamic biomarker

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Area of Science:

  • Genomics
  • Molecular Biology
  • Psychiatry

Background:

  • Molecular biomarkers for depression are lacking, hindering objective patient stratification and recovery monitoring.
  • Transcriptomic research has yet to yield clinically robust biomarkers for depression.
  • Intron retention (IR) is proposed as a potential biomarker reflecting homeostatic adaptation to stress.

Purpose of the Study:

  • To review evidence supporting intron retention (IR) as a sensitive biomarker for stress adaptation and recovery in depression.
  • To explore the mechanistic role of IR in fine-tuning gene output and its potential as a disease marker.
  • To evaluate the clinical utility of IR signatures as pharmacodynamic metrics for monitoring treatment response.

Main Methods:

  • Review of existing evidence on intron retention (IR) in the context of depression.
  • Analysis of IR patterns in response to interventions like hangekobokuto (HKT) and ketamine.
  • Exploration of IR as a biomarker for early cognitive decline (mild cognitive impairment).

Main Results:

  • Intron retention (IR) signatures can precede or outperform differential gene expression (DEG) readouts in reflecting disease state.
  • Increased IR (IncIR) throttles gene output under stress, while decreased IR (DecIR) restores it, indicating a homeostatic regulatory role.
  • IR normalization was observed with hangekobokuto (HKT) treatment, correlating with reduced inflammation; distinct IR patterns in ketamine non-responders suggest higher inflammatory load.

Conclusions:

  • Intron retention (IR) shows potential as a sensitive, upstream biomarker for depression, reflecting stress adaptation and treatment response.
  • IR signatures are reversible and treatment-responsive, making them suitable for blood-based monitoring of drug efficacy and recovery.
  • The transdiagnostic applicability of IR biomarkers warrants further investigation in conditions like mild cognitive impairment (MCI).