As reported on MedicalXpress, a new study published in Molecular Psychiatry suggests that a specific circular RNA found in blood, known as CDR1as, may help forecast how patients with major depressive disorder (MDD) respond to certain antidepressants, potentially paving the way toward more personalized treatment strategies.
A Step Toward Precision Psychiatry
MDD affects hundreds of millions of people worldwide, yet clinicians still rely heavily on trial-and-error to identify effective treatments. Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed antidepressants, but many patients must cycle through several medications before finding one that works.
Researchers from Circular Genomics Inc., the University of New Mexico, Fondation FondaMental, and collaborating institutions have identified CDR1as—a stable, brain-enriched circular RNA detectable in blood—as a potential predictor of SSRI treatment outcomes.
CDR1as Linked to Sertraline Response
The team analyzed blood samples collected before treatment from participants in two major clinical studies: EMBARC and ANTARES. They compared baseline CDR1as levels in individuals who later showed significant symptom improvement on sertraline with those who did not benefit from the drug.
Their analyses revealed that patients who eventually responded to sertraline had distinguishable CDR1as levels prior to starting therapy. Additional datasets from naturalistic treatment cohorts supported this association across the broader SSRI drug class.
Changes in CDR1as After Treatment
Beyond baseline patterns, the researchers observed that CDR1as levels shifted after treatment in patients who achieved remission, and the pattern of change aligned with long-term outcomes. Notably, the biomarker did not predict improvement in individuals who received either placebo or the non-SSRI antidepressant bupropion, suggesting its specificity for serotonergic medications.
To explore the underlying biology, the team also conducted animal and neuronal culture experiments. These studies indicated that CDR1as levels are influenced by serotonin receptor signaling and brain-derived neurotrophic factor (BDNF), two pathways deeply involved in antidepressant mechanisms.
Implications for Personalized Depression Care
If validated in larger trials, measuring CDR1as in standard blood samples could significantly reduce the time patients spend cycling through ineffective medications. The study focused on sertraline, but the authors suggest future work may test whether the biomarker predicts response to other commonly used SSRIs such as fluoxetine or escitalopram.
The investigators conclude that CDR1as represents a biologically meaningful and clinically actionable marker that could support more precise treatment selection for individuals with depression—offering hope for more streamlined, effective care.
