PMID- 28599751 OWN - NLM STAT- MEDLINE DCOM- 20181031 LR - 20220321 IS - 1573-2509 (Electronic) IS - 0920-9964 (Linking) VI - 192 DP - 2018 Feb TI - Association between serum levels of glutamate and neurotrophic factors and response to clozapine treatment. PG - 226-231 LID - S0920-9964(17)30314-6 [pii] LID - 10.1016/j.schres.2017.05.040 [doi] AB - 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. CI - Copyright (c) 2017. Published by Elsevier B.V. FAU - Krivoy, Amir AU - Krivoy A AD - Geha Mental Health Center, Petach-Tikva, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Petach-Tikva, Israel; Department of Psychosis Studies, Institute Of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Electronic address: akrivoy@clalit.org.il. FAU - Hochman, Eldar AU - Hochman E AD - Geha Mental Health Center, Petach-Tikva, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Petach-Tikva, Israel. FAU - Sendt, Kyra-Verena AU - Sendt KV AD - Department of Psychosis Studies, Institute Of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. FAU - Hollander, Sarah AU - Hollander S AD - Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Petach-Tikva, Israel. FAU - Vilner, Yael AU - Vilner Y AD - Geha Mental Health Center, Petach-Tikva, Israel. FAU - Selakovic, Mirjana AU - Selakovic M AD - Department of Psychiatry, Sismanoglio General Hospital, Athens, Greece. FAU - Weizman, Abraham AU - Weizman A AD - Geha Mental Health Center, Petach-Tikva, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Petach-Tikva, Israel. FAU - Taler, Michal AU - Taler M AD - Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Petach-Tikva, Israel. LA - eng PT - Journal Article PT - Observational Study DEP - 20170607 PL - Netherlands TA - Schizophr Res JT - Schizophrenia research JID - 8804207 RN - 0 (Antipsychotic Agents) RN - 0 (Nerve Growth Factors) RN - 3KX376GY7L (Glutamic Acid) RN - J60AR2IKIC (Clozapine) SB - IM CIN - Schizophr Res. 2018 Mar;193:487-488. PMID: 28821358 MH - Adult MH - Antipsychotic Agents/*therapeutic use MH - Clozapine/*therapeutic use MH - Cross-Sectional Studies MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Glutamic Acid/*blood MH - Humans MH - Male MH - Middle Aged MH - Nerve Growth Factors/*blood MH - Psychiatric Status Rating Scales MH - Schizophrenia/*blood/*drug therapy MH - Statistics, Nonparametric OTO - NOTNLM OT - Biomarker OT - Growth factor OT - Neurotransmitter OT - Psychosis OT - Refractory OT - Resistant OT - Schizophrenia EDAT- 2017/06/11 06:00 MHDA- 2018/11/01 06:00 CRDT- 2017/06/11 06:00 PHST- 2017/02/09 00:00 [received] PHST- 2017/05/07 00:00 [revised] PHST- 2017/05/30 00:00 [accepted] PHST- 2017/06/11 06:00 [pubmed] PHST- 2018/11/01 06:00 [medline] PHST- 2017/06/11 06:00 [entrez] AID - S0920-9964(17)30314-6 [pii] AID - 10.1016/j.schres.2017.05.040 [doi] PST - ppublish SO - Schizophr Res. 2018 Feb;192:226-231. doi: 10.1016/j.schres.2017.05.040. Epub 2017 Jun 7.