Blood Protein Golga3 Found at Lower Levels in Schizophrenia Patients

A small but intriguing case-control study from Türkiye has added a new molecular suspect to the long list of biological players implicated in schizophrenia. Researchers report that patients with schizophrenia carry significantly reduced levels of a protein called Golga3 in their blood plasma, hinting that a previously underappreciated cellular pathway involving the Golgi apparatus and the neurotransmitter modulator D-serine may be disrupted in the illness. The findings, published in BMC Psychiatry, offer a fresh angle on one of psychiatry’s most stubborn puzzles: the biological basis of a disorder that affects roughly one in every hundred people worldwide.

The protein at the center of the study, Golga3, is better known to cell biologists as a structural component of the Golgi apparatus, the membrane-bound organelle that packages and ships proteins inside cells. But Golga3 has a second, more surprising job. It helps regulate the stability of an enzyme called serine racemase, which converts the amino acid L-serine into its mirror-image form, D-serine. D-serine is no molecular footnote: it binds to the glycine site of the N-methyl-D-aspartate receptor, a glutamate-sensitive receptor that is essential for learning, memory, and synaptic plasticity. By inhibiting the ubiquitin-tagged, proteasome-driven degradation of serine racemase, Golga3 effectively keeps D-serine production running. Less Golga3, the reasoning goes, could mean less serine racemase, and ultimately less D-serine available to support NMDA receptor function.

That chain of logic matters because the NMDA hypofunction hypothesis has become one of the leading neurobiological accounts of schizophrenia. Decades of evidence, from the psychotomimetic effects of ketamine and phencyclidine, which block the NMDA receptor, to postmortem and genetic studies, suggest that weakened signaling through this receptor contributes to the positive symptoms of psychosis, the negative symptoms such as social withdrawal and blunted affect, and the cognitive difficulties that so often define the long-term course of the illness. D-serine itself has been tested as an add-on treatment in clinical trials, with mixed but sometimes encouraging results. If Golga3 sits upstream of D-serine availability, its reduction could represent a measurable molecular signature of the same pathway.

To test that idea, a team led by Eda Uzun Uysal and Bahri İnce of the Bakirkoy Prof. Dr. Mazhar Osman Training and Research Hospital for Psychiatry, Neurology and Neurosurgery in Istanbul, together with Ömer Alper Uysal of Eyüpsultan State Hospital, recruited three carefully matched groups. The first comprised 24 patients with schizophrenia who responded to standard antipsychotic monotherapy, a category researchers call non-treatment-resistant schizophrenia. The second comprised 24 patients whose illness had proved resistant to conventional treatment and who were being managed with clozapine, the gold-standard medication for treatment-resistant schizophrenia. The third group consisted of 26 healthy controls. Critically, the groups were matched for age, sex, education, and smoking status, factors that can otherwise confound comparisons of blood-based biomarkers.

The measurement protocol was deliberately standardized. Venous blood samples were drawn in the morning after an overnight fast, reducing the chance that circadian rhythms or recent meals would skew protein levels. Plasma concentrations of Golga3 were then quantified using an enzyme-linked immunosorbent assay, or ELISA, a technique that uses antibodies to capture and quantify a specific protein in a biological sample. Alongside the blood work, the clinicians assessed symptom severity using the Positive and Negative Syndrome Scale, the standard instrument for rating psychotic symptoms, and the Global Assessment Scale, which captures overall functional impairment. This dual approach allowed the researchers to ask not only whether Golga3 differed between groups, but whether its levels tracked with the clinical picture.

The answer to the first question was a clear yes. Plasma Golga3 levels varied significantly across the three groups, with an overall statistical significance of p less than 0.001. Post-hoc comparisons showed that both patient groups differed from the healthy controls: patients on standard antipsychotic monotherapy had significantly lower Golga3 than controls, with a p value of 0.001, and so did the clozapine-treated, treatment-resistant patients, with a p value of 0.002. Strikingly, however, the two patient groups were statistically indistinguishable from each other, with a p value of 0.722. Whatever is driving the reduction in Golga3, it appears to be shared across the illness rather than tied specifically to treatment resistance or to clozapine exposure.

The answer to the second question was more sobering. The researchers found no significant correlations between plasma Golga3 levels and any of the clinical variables they measured, including symptom scores on the PANSS and functional ratings on the GAS. In other words, patients with lower Golga3 were not reliably more symptomatic or more impaired than patients whose levels were closer to the control range. That absence of a dose-response relationship is a common feature of early biomarker studies and tempers any temptation to treat Golga3 as a diagnostic or prognostic test. It suggests instead that reduced Golga3 may mark a pathway-level vulnerability that is present in schizophrenia broadly, rather than a dial that tracks day-to-day symptom fluctuation.

The authors themselves are careful about scope. They describe the findings as preliminary and emphasize that the study was designed to detect whether changes in the Golga3-serine racemase pathway are present in schizophrenia at all, not to establish the pathway’s functional consequences. Because the study measured Golga3 but not D-serine or serine racemase directly, the intermediate steps of the hypothesized cascade remain unverified in this cohort. It is possible that reduced plasma Golga3 reflects altered Golgi function, altered protein degradation, or even a peripheral readout of a central nervous system process, but the study cannot yet distinguish among these interpretations. The authors call explicitly for future work examining D-serine levels and related metabolic markers to clarify what the reduction means biologically.

Several limitations frame how the results should be read. The sample sizes, while adequate for detecting group differences of the magnitude observed, are modest, and case-control designs of this kind capture a snapshot rather than a trajectory. All patients were taking antipsychotic medication, so the possibility that treatment influences Golga3 levels cannot be excluded, although the similarity between patients on monotherapy and those on clozapine offers some reassurance. Plasma is also a peripheral compartment; whether blood levels mirror what happens in the brain, where serine racemase and D-serine do their synaptic work, is an open question that will require imaging, postmortem, or cerebrospinal fluid studies. Replication in independent, ideally medication-naive or first-episode cohorts would strengthen confidence that the finding is intrinsic to the illness rather than an artifact of sampling or treatment.

Even with those caveats, the study is notable for pointing a spotlight at the Golgi apparatus, an organelle rarely invoked in mainstream schizophrenia research, and for connecting it to the glutamatergic machinery that many researchers consider central to the disorder. Biomarkers that can be measured in a fasting blood draw are attractive targets for psychiatry, a field still lacking objective laboratory tests for its major diagnoses. If follow-up studies confirm that Golga3, serine racemase, and D-serine move together in patients, and if the reduction proves specific to schizophrenia rather than psychosis in general, the pathway could eventually inform both patient stratification and drug development aimed at enhancing NMDA receptor function. For now, the message is one of cautious excitement: a single protein, measured in blood, has opened a new window onto the biology of schizophrenia, and the view through it is only beginning to come into focus.

Subject of Research: Reduced plasma Golga3 and the Golga3-serine racemase-D-serine pathway in schizophrenia

Article Title: Reduced plasma Golga3 levels in patients with schizophrenia: a case-control study

Article References: Uzun Uysal, E., Uysal, Ö. A., & İnce, B. (2026). Reduced plasma Golga3 levels in patients with schizophrenia: a case-control study. BMC Psychiatry. https://doi.org/10.1186/s12888-026-08685-8

Image Credits: AI Generated

DOI: 10.1186/s12888-026-08685-8

Keywords: schizophrenia, Golga3, D-serine, serine racemase, NMDA hypofunction, glutamate, plasma biomarkers, psychosis, treatment-resistant schizophrenia, clozapine, psychopharmacology, case-control study