Evidence map›Paper›PMID 42289593›Full record

Observational studyScientific reports2026

Central and peripheral glutamatergic biomarkers delineate heterogeneous clinical phenotypes in olanzapine-treated schizophrenia.

Wirginia Krzyściak, Maciej Pilecki, Beata Bystrowska, Marta Szwajca, Natalia Śmierciak, Aleksander Turek, Paulina Karcz, Amira Bryll, Paulina Mazur, Ewa Gomółka and 1 more

Abstract readObservational Study
In one paragraph

Observational study in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

11 authors.

Wirginia KrzyściakDepartment of Medical Diagnostics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, 30-688, Poland. wirginia.krzysciak@uj.edu.pl.
Maciej PileckiDepartment of Child and Adolescent Psychiatry and Psychotherapy, Chair of Psychiatry, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 31-501, Poland.
Beata BystrowskaDepartment of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, 30-688, Poland.
Marta SzwajcaDepartment of Child and Adolescent Psychiatry and Psychotherapy, Chair of Psychiatry, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 31-501, Poland.
Natalia ŚmierciakDepartment of Child and Adolescent Psychiatry and Psychotherapy, Chair of Psychiatry, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 31-501, Poland.
Aleksander TurekDepartment of Child and Adolescent Psychiatry and Psychotherapy, Chair of Psychiatry, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 31-501, Poland.
Paulina KarczDepartment of Electroradiology, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, 31-126, Poland.
Amira BryllDepartment of Radiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 31-501, Poland.
Paulina MazurDepartment of Medical Diagnostics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, 30-688, Poland.
Ewa GomółkaToxicological Information Center, Department of Clinical Toxicology and Environmental Diseases, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 31-503, Poland.
Tadeusz PopielaDepartment of Radiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 31-501, Poland.

Funding

Jagiellonian University Medical College, Poland N42/DBS/000452National Science Centre, Poland 2024/08/X/NZ7/00479the Priority Research Area BioS under the Excellence Initiative-Research University program at the Jagiellonian University in Krakow U1C/P03/NO/03.36
6 · The paper itself

Abstract

This study aimed to identify central and peripheral glutamatergic biomarkers underlying heterogeneous clinical phenotypes in olanzapine-treated patients with schizophrenia, with the goal of informing biomarker-guided personalized therapy. We conducted a cross-sectional observational study of 51 adults with schizophrenia receiving chronic olanzapine treatment (mean duration = 5.6 years), integrating clinical assessments with peripheral neurochemical profiling and magnetic resonance spectroscopy (MRS) of the anterior and posterior cingulate cortices. Partial correlations controlling for age, sex, and treatment duration revealed significant associations: higher serum serotonin correlated with more severe negative symptoms (ρ = 0.32, p = 0.029), and increased cingulate Glx ratios were linked to greater depressive burden (ρ = 0.31, p = 0.031). Elevated serum glutamic acid was associated with overall psychopathology, whereas lower serum and cingulate glutamine levels were related to more severe symptoms and higher olanzapine exposure. Hierarchical clustering on principal components (HCPC) identified three phenotypic subgroups: (1) low-symptom, dose-efficient responders; (2) high-symptom, dose-resistant patients with cingulate hypoglutamatergia; and (3) younger individuals with elevated Glx ratios and moderate exposure, suggestive of a hyperglutamatergic, neurodevelopmental profile. These findings demonstrate that central and peripheral glutamatergic markers delineate distinct clinical phenotypes of olanzapine response in schizophrenia, shaped by both neurochemical and demographic factors. Stratification based on glutamatergic profiles and symptom patterns may contribute to the development of precision psychiatry approaches. To our knowledge, this is the first study to integrate central and peripheral glutamatergic biomarkers with multivariate phenotyping in a naturalistic olanzapine-treated cohort, identifying (i) a low-symptom, low-exposure phenotype, (ii) a high-symptom, high-exposure phenotype characterised by reduced cingulate Glx, and (iii) a younger phenotype with elevated cingulate Glx ratios, consistent with, though not confirmatory of, a neurodevelopmental trajectory. These findings are exploratory and warrant prospective validation to determine their potential utility for biomarker-guided treatment stratification in schizophrenia.

Indexed as

Antipsychotic AgentsGlutamic AcidOlanzapineSchizophreniaAdultBiomarkersCross-Sectional StudiesFemaleGlutamineGyrus CinguliHumansMagnetic Resonance SpectroscopyMaleMiddle AgedPhenotypeSerotoninAntipsychotic AgentsBiomarkersGlutamic AcidGlutamineOlanzapineSerotoninMagnetic resonance spectroscopyMultivariate analysisNeurochemical biomarkersOlanzapinePersonalized psychiatrySchizophrenia

Identifiers

PMID42289593
PMCPMC13527110

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.