A new circular RNA-based blood test could predict depression treatment responses

Written by Emma Hall (Contributing Editor)

Personalized depression treatment is now becoming a reality with Circular Genomics’ (NM, USA) novel circular RNA (circRNA)-based blood test, which could be capable of predicting patients’ responses to selective serotonin reuptake inhibitors (SSRIs).

Circular Genomics have identified a brain-enriched circRNA-based blood biomarker that is regulated by both serotonin 5-HT2A and brain-derived neurotrophic factor receptor activity. The study, known as Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC), identified and validated a circRNA biomarker as an accurate predictor of patient SSRI responses. This new circRNA biomarker was at almost 80% higher baseline levels in patients who failed to respond to sertraline (an SSRI), compared to patients who responded.

Depression is a common mental health disorder affecting 5% of adults globally. Left untreated, depression can severely impact an individual’s psychological and physical wellbeing. Although there are effective treatments for depression, including therapy and medication, most individuals undergo a trial-and-error approach for different medications before finding the most effective antidepressant. Consequently, to optimize treatment selection and therefore depression management, it is important to accurately predict an individual’s response to different antidepressants. This is what Circular Genomics set out to do with SSRIs, as they are the most commonly prescribed class of antidepressants.


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Interestingly, the circRNA-based biomarker exclusively forecasted SSRI outcomes, unrelated to placebos or other antidepressants. Post-treatment, the biomarker levels dynamically changed, potentially enabling continuous monitoring and long-term recovery prediction. Additionally, the expression of the circRNA correlates with crucial molecular pathways implicated in the SSRI response, including serotonin 5-HT2A and brain-derived neurotrophic factor receptor signaling.

“Our data provide evidence that blood levels of a brain-enriched circRNA associated with known mechanisms of antidepressant response can accurately predict response to SSRIs and remission in patients with major depressive disorder,” commented Nikolaos Mellios, Co-founder and CSO of Circular Genomics. “These findings reinforce our belief that the expression of specific circRNAs in the blood can act as an indirect ‘window into the brain’ and provide actionable insights for the better diagnosis and treatment of brain disorders.”

With plans to release the first circRNA-based test later this year, Circular Genomics aims to combat the high therapy failure rates and suboptimal clinical outcomes prevalent in the current depression treatment landscape. The company’s technology holds promise not only for depression but also for a range of psychiatric and neurological disorders, heralding a new era of precision medicine.