Cheek cells may provide clues to schizophrenia risk

Sp4 mRNA expression in buccal cells correlates with poorer performance on the recognition portion of the HVLT-R. Credit: Science Advances (2026). DOI: 10.1126/sciadv.aeb0460

A simple cheek swab could one day provide a quick and noninvasive diagnostic test for schizophrenia. A new study published in Science Advances has identified higher levels of two biological markers in the cheek swabs of patients with schizophrenia compared with people who don’t have this mental health disorder. Schizophrenia is a long-term condition with a range of symptoms including hallucinations, delusions, muddled thoughts and loss of interest in everyday activities.

Diagnosis is challenging

There is no single test for the illness, and diagnosis can be challenging because symptoms vary widely between people and typically relies on observing a patient’s behavior. It can, therefore, sometimes take months for a professional to make a diagnosis with any degree of certainty, as they have to rule out other possible causes. That is a lot of time for someone to wait without the right treatment if it is needed.

So researchers led by a team at Rutgers University in New Jersey decided to investigate whether molecular signatures in easy-to-collect buccal (cheek) cells could serve as reliable biomarkers.

They recruited 27 people diagnosed with schizophrenia and 27 healthy control volunteers who were matched by age, race and gender and collected samples from inside each participant’s cheeks.

These samples were analyzed using RT-qPCR (reverse transcription quantitative polymerase chain reaction), which measures the amount of RNA in a sample to assess the activity of specific genes. They focused on three genes previously linked to an increased risk of schizophrenia, then used mass spectrometry to see whether any related proteins differed between patients and controls.

Key findings

Patients with schizophrenia had significantly higher levels of activity in the Sp4 gene compared to the control group. This gene plays a role in how the brain develops. High levels of activity were associated with more severe symptoms, such as hallucinations and delusions.

The researchers also found larger amounts of HSP60, which is thought to be regulated by Sp4.

“Our data suggest that Sp4 mRNA expression and its downstream target HSP60 are potential biomarkers of SCZ,” wrote the scientists. “Our study reports buccal cell biomarkers that correlate with cognitive deficits observed in patients with SCZ.”

According to the researchers, these markers could be effective indicators because the central nervous system and the skin in our mouths both develop from the same embryonic tissue (ectoderm). Therefore, cheek swabs can provide us with clues about what is happening in the brain.

While the results are fascinating, larger studies are needed to confirm if these biomarkers are specific to schizophrenia. If they prove successful, a simple swab could not only help achieve earlier detection but also potentially monitor the progression of the illness.

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