New Saliva Test May Reveal Early Signs of Depression and Schizophrenia

Researchers have developed a disposable, low-cost biosensor capable of rapidly detecting the neurotrophic factor BDNF, a protein linked to depression, directly in saliva. The device uses a sensitive electrochemical technique, with results in less than three minutes and a cost of less than US$2. This technology could revolutionize the early diagnosis and monitoring of mood disorders and neurological diseases in a non-invasive and accessible way.

Mood disorders, such as depression and bipolar disorder, are among the most common and disabling mental illnesses in the world. Depression alone affects nearly 280 million people, according to the World Health Organization, and can cause loss of productivity, social isolation, and, in severe cases, lead to suicide.

Despite medical advances, much remains to be understood about the biological causes of these disorders and how to diagnose them early.

Recent research suggests that depression is linked to alterations in neurotrophins, proteins that help the brain grow, adapt, and regenerate. Among them, Brain-Derived Neurotrophic Factor (BDNF) is considered one of the main biological markers associated with depression and other neurological diseases, such as Alzheimer's and Parkinson's.

Low levels of BDNF have been observed in people with depressive symptoms and may indicate a reduced capacity of the brain to create new neural connections, contributing to memory loss, apathy, and cognitive slowness. This hypothesis, known as the "neurotrophic hypothesis of depression," proposes that restoring BDNF in the brain may aid in emotional recovery, and indeed, many antidepressants appear to act indirectly by increasing this factor.

The major challenge, however, is measuring BDNF quickly, cheaply, and accessibly. Traditional methods used in laboratories, such as enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence, and high-performance liquid chromatography (HPLC), are highly accurate but require expensive equipment, specialized personnel, and long processing times.

These limitations prevent routine clinical use or direct point-of-care diagnosis (e.g., in clinics or pharmacies).

To overcome these barriers, researchers have developed a new electrochemical method capable of detecting BDNF quickly, non-invasively, and at low cost. This method is based on a disposable biosensor, a small strip that functions as a "rapid test," similar to a blood glucose test, but designed to detect BDNF in human saliva. Saliva was chosen because it is an easy fluid to collect, painless, and representative of the body's biochemical state, as it contains molecules that also circulate in the blood.

The biosensor is made of a screen-printed carbon electrode, that is, a flat, electrically conductive device that is inexpensive and easy to produce on a large scale. On this surface, scientists applied carbon spheres and polyethyleneimine (PEI), a substance that increases the contact area and improves the adhesion of molecules, as well as glutaraldehyde, which helps to stably fix antibodies.

These antibodies are specific for BDNF: when the biomarker is present in saliva, it binds to these antibodies, altering the electrical properties of the sensor. This change is then detected by electrochemical impedance spectroscopy (EIS), a technique that measures how the electrical current is affected by this molecular interaction.

The result is obtained in less than three minutes, with very high sensitivity: the sensor can detect minuscule amounts of BDNF, on the order of 10⁻²⁰ grams per milliliter, making it much more sensitive than conventional methods. Furthermore, it is reusable only once, completely disposable, and costs less than US$2.20 per unit.

The biosensor was tested with saliva samples from healthy volunteers, showing high selectivity (detects only BDNF, without interference from other proteins), reproducibility (consistent results between tests), stability (maintains accuracy over time), and robustness (works even under non-ideal storage conditions).

To assess the environmental impact of the device, the researchers applied sustainability analysis tools such as the Analytical Ecological Scale (AES), the Analytical Sustainability Index (AGREE), and the Blue Index (BAGI), which measures the “ecological practicality” of the method. All analyses indicated that the biosensor is environmentally sustainable and suitable for clinical or home use.

This new device represents a major advance in the area of ​​rapid and personalized mental health diagnosis. It allows for simple and safe monitoring of BDNF, without the need for punctures or specialized laboratories.

With minor adaptations, technologies like this could be used in the future to monitor responses to antidepressants, diagnose neurological disorders early, or even assess stress and well-being levels in real time, directly from the patient's saliva.

READ MORE:

Low-Cost, Disposable Biosensor for Detection of the Brain-Derived  Neurotrophic Factor Biomarker in Noninvasively Collected Saliva toward Diagnosis of Mental Disorders

Nathalia O. Gomes, Marcelo L. Calegaro, Luiz Henrique C. Mattoso, Sergio A. S. Machado, Osvaldo N. Oliveira Jr., and Paulo A. Raymundo-Pereira

ACS Polym. Au 2025, 5, 4, 420–431

https://doi.org/10.1021/acspolymersau.5c00038

Abstract:

The importance of early detection of neurodegenerative disorder biomarkers has grown since these biomarkers are essential for timely diagnosis, treatment, healthcare, and wellness applications. We present a cost-effective and disposable electrochemical immunosensing strip for rapid, decentralized detection of brain-derived neurotrophic factor (BDNF), one of the major neurotrophins (NTs) associated with neurological and psychiatric disorders, in human saliva. The salivary BDNF immunosensor strip is made on a screen-printed carbon electrode functionalized with carbon spherical shells (CSSs), polyethylenimine (PEI), and glutaraldehyde to enhance sensitivity. Through systematic optimization, the sensor achieved excellent analytical performance, with a wide dynamic detection range from 1.0 × 10–20 to 1.0 × 10–10 g mL–1, a rapid response time of under 3 min, and an ultralow detection limit of 1.0 × 10–20 g mL–1 for BDNF in human saliva. The BDNF immunosensor demonstrated high selectivity, reproducibility, robustness, stability, and long-term storage capability. At a cost of less than US$ 2.19 per unit, this disposable sensor also enabled rapid BDNF detection in saliva samples collected from healthy volunteers without interference from other salivary constituents. The environmental impact was assessed using the Analytical Eco-Scale (AES), the Analytical GREEnness Metric Approach (AGREE), and the Blue Applicability Grade Index (BAGI), which evaluates the practicality (“blueness”) of the device. These assessments confirmed the sustainability of the disposable BDNF immunosensor strip. This device provides a rapid, efficient, cost-effective, and reliable method for the decentralized, noninvasive salivary analysis of BDNF, enabling broader applications in healthcare, wellness monitoring, and medical diagnostics related to the neurotrophin family of biomarkers.