Association between serum levels of glutamate and neurotrophic factors and response to clozapine treatment
Abstract
Clozapine is the only available therapy for about 30% of schizophrenia patients otherwise refractory to antipsychotics. Unfortunately, the mechanism of action of the drug is still unknown and there are no biomarkers that can predict a positive response to clozapine. We aimed to examine serum neurotrophins and glutamate levels as putative biomarkers for clozapine response based on the hypothesized mode-of-action of the compound. Blood samples of 89 chronic schizophrenia patients maintained on clozapine were analyzed in a cross-sectional design. Serum brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), neurotrophic growth factor (NGF), glial derived neurotrophic factor (GDNF) and glutamate were determined. Differences between responders and non-responders to clozapine and correlation between clinical and biological measures were analyzed. Our sample consisted of 54 (61%) responders and 35 (39%) non-responders. Responders had higher mean BDNF levels than non-responders (2066±814 vs. 1668±820pg/ml, p<0.05. respectively) and higher serum glutamate levels (1.61±2.2 vs. 0.66±0.9pg/ml, respectively, p<0.05). Furthermore, there was a significant correlation between serum glutamate levels and positive symptoms among the clozapine-responder group (rho=0.47, p<0.005). High serum levels of BDNF and glutamate were associated with response to clozapine, while glutamate levels correlated with the psychosis severity in clozapine responders only. Large-scale, prospective longitudinal studies are needed to support these findings and the assumption that serum glutamate and BDNF can discriminate between clozapine responders and non-responders.
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Some studies suggest that baseline BDNF levels in schizophrenia patients might reflect the susceptibility towards available drug therapies.
“In addition, some studies suggest that baseline BDNF levels in schizophrenia patients might reflect the susceptibility towards available drug therapies [129, 130].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [129]
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Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation
Lima Giacobbo, B., Doorduin, J., Klein, H. C., Dierckx, R. A. J. O., Bromberg, E., & de Vries, E. F. J. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1283-6 · Cited by 750 · see citing works
- Authors
- Krivoy, A., Hochman, E., Sendt, K.-V., Hollander, S., Vilner, Y., Selakovic, M., Weizman, A., & Taler, M.
- Affiliations
- Tel Aviv University (IL)
- King's College London (GB)
- Geha Mental Health Center (IL)
- Corresponding author
- Krivoy, Amir
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 192
- Pages
- 226-231
- ISSN
- 0920-9964 (ISSN-L)
- OpenAlex
- W2622085535
- Cited by
- 33
- References
- 56
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 1
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- clozapine, schizophrenia
- MeSH terms
- Adult, Clozapine, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Nerve Growth Factors, Psychiatric Status Rating Scales, Schizophrenia, Antipsychotic Agents, Glutamic Acid, Statistics, Nonparametric
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