Precision Psychiatry: A Paradigm Shift for Mental Healthcare
While medicine has traditionally aimed to be personalized, it has rarely been precise.
As a resident doctor, I have seen firsthand how many of the first-line medications we use to treat some of the most common diseases in the hospital often prove ineffective and come with significant side effects. When first-line treatments fail, we trial second-line therapies until something works. In this approach, we treat the disease rather than the patient.
Medicine today often feels like a process of trial and error because individual responses to treatment can vary widely. Historically, diseases were assumed to affect all patients similarly, but in reality, patient variability can lead to vastly different health outcomes even within the same diagnostic category. The increasing emphasis on precision medicine has greatly improved our capacity to customize treatments based on an individual’s genetics, environment, lifestyle, and specific disease type. While precision medicine has achieved notable advancements in various fields, including oncology, immunotherapy, and cardiology, it has received comparatively little attention and investment in psychiatry.
Yet psychiatry is the field where precision medicine is needed most. Nearly half of all people in the United States will be diagnosed with a mental health disorder in their lifetime. For these patients, three main barriers hinder meaningful improvement: limited access to mental healthcare providers, ineffective medications, and high rates of misdiagnosis.
The first barrier, inadequate access to care, is one many digital startups are tackling — unsuccessfully. With roughly 340 individuals for every mental healthcare provider in the country, no matter how many apps are developed to facilitate mental healthcare, the fundamental problem persists: there simply aren’t enough quality providers.
The second barrier, ineffective medications, is one that many are unaware of. Taking a pill for a mental health diagnosis does not guarantee improvement of symptoms. Selective Serotonin Reuptake Inhibitors (SSRIs), for example, the first-line class of medications for depression, anxiety, and PTSD, fail a majority of patients. The trial-and-error approach in psychiatry means finding the right drug for a patient can take years and comes with significant costs, to the patient and society.
The third barrier, high misdiagnosis rates, is alarming but unsurprising, with rates for some common mental health disorders exceeding 80%. Psychiatry, like other medical fields, uses classification systems such as the DSM-5 and ICD-11, but it stands apart in having undergone multiple overhauls of its foundational knowledge. Within each DSM-5 and ICD-11 category, there is immense variability. One study found 636,120 ways to present with PTSD. Diagnosis also relies on subjective clinician-led interviews and surveys, inviting human error. With such heterogeneity and subjectivity, it’s clear the diagnostic and treatment processes need improvement.
In the next decade, precision medicine in psychiatry promises to address the second and third barriers. At its core, precision medicine focuses on biomarkers — measurable characteristics that indicate biological processes, disease states, or treatment responses, enabling more tailored and effective interventions. Biomarkers will supplant subjectivity with objectivity in mental healthcare. Today, pioneers in Precision Psychiatry are exploring biomarkers to help clinicians better categorize diseases and guide treatment.
Circular Genomics
In the ever-evolving landscape of healthcare, Circular Genomics, a private company that just closed a $8.3MM Series A round earlier this year, stands out as a trailblazer in the pursuit of precision medicine in psychiatry. Co-founded by Dr. Nikoloas Mellios, a neuroscientist and former physician, the company is leveraging innovative biomarkers to transform the diagnosis and treatment of psychiatric disorders.
“The currently available biomarker approaches do not address the unique challenges of psychiatry,” Dr. Mellios explains. To accurately diagnose and treat psychiatric conditions, “we need robust biomarkers derived from the brain itself and accurate and reproducible laboratory assays that are readily accessible and easy to deploy in everyday clinical practice.”
Circular RNA (circRNA) represents a novel class of non-coding RNA predominantly found in brain tissue. Unlike its linear counterparts, circRNA is resistant to degradation, allowing for prolonged detection in the bloodstream. Its sensitivity to neuronal receptor activation and blood-brain barrier permeability makes it invaluable for monitoring brain changes. Dr. Mellios describes these biomarkers as “a molecular window into the processes of the brain.”
Circular Genomics’ circular RNA biomarker, CircRNAx, has shown remarkable stability, largely unaffected by external factors like time of day or lifestyle. Its expression significantly alters only when treatment begins, establishing it as a reliable predictor of psychiatric treatment responses.
The implications of CircRNAx are profound. This single circular RNA has demonstrated an impressive close to 80% accuracy in predicting treatment outcomes of SSRIs in depression — a remarkable feat in the realm of mental healthcare. Moreover, ongoing studies aim to diagnose Alzheimer’s disease with an accuracy exceeding 95%, indicating the far-reaching potential of circRNA biomarkers.
With the September release of their flagship product, Mindlight, Dr. Mellios reflects on the potential of existing medications like SSRIs. While these antidepressants are effective only for a subset of patients, he notes that “we can use all these available drugs effectively by matching them to the proper patients,” underscoring the importance of identifying those who would benefit most. Mindlight’s circRNA biomarker enables more precise selection of patients likely to respond to SSRI treatment. The goal is to establish a new paradigm in psychiatry where treatment responses are accurately predicted across various medications, creating a more efficient pathway to care and potentially reducing costs for both patients and the healthcare system.
Psychiatry is a field ripe for disruption, having historically been stigmatized, overlooked, and undervalued. Many still fail to recognize that psychiatric disorders have biological underpinnings. This misunderstanding leads to reduced funding for mental health research at institutions, resulting in fewer breakthroughs. As Dr. Mellios states, “We need a Manhattan Project for mental health.”
The future of psychiatry lies in precision medicine, where treatments are tailored to the unique biology of each patient, moving beyond the limitations of trial-and-error. With innovative biomarkers like circRNA, companies such as Circular Genomics are redefining mental healthcare, offering the potential for accurate diagnoses and targeted treatments that reduce suffering, improve outcomes, and lower costs. As we push toward this paradigm shift, investing in psychiatric research and embracing biologically grounded approaches will be essential to creating a new era of personalized, effective mental healthcare.
