PMID- 30140973 OWN - NLM STAT- MEDLINE DCOM- 20190813 LR - 20200225 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 56 IP - 5 DP - 2019 May TI - Crosstalk Between Inflammation and Glutamate System in Depression: Signaling Pathway and Molecular Biomarkers for Ketamine's Antidepressant Effect. PG - 3484-3500 LID - 10.1007/s12035-018-1306-3 [doi] AB - Depression is a worldwide illness with a significant impact on both family and society. Conventional antidepressants are ineffective for more than 30% of patients. In such patients, who have what is called treatment-resistant depression (TRD), inflammatory biomarkers are expressed excessively in both the central nervous system (CNS) and the peripheral blood. Ketamine, a glutamate receptor antagonist, exerts a rapid and sustained therapeutic effect in patients with TRD. Thus, the investigation of the relations between inflammation and glutamate underlying depression has drawn great attention. Inflammation influences glutamate release, transmission, and metabolism, resulting in accumulated extracellular glutamate in the CNS. Downstream of the glutamate receptors, the mammalian target of rapamycin (mTOR) signaling pathway plays a key role in mediating ketamine's antidepressant effect by improving neurogenesis and plasticity. Based on the mechanism and clinical evidence of the inflammatory contribution to the pathogenesis of depression, extensive research has been devoted to inflammatory biomarkers of the clinical response of depression to ketamine. The inconsistent findings from the biomarker investigations are at least partially attributable to the heterogeneity of depression, limited sample size, and complex gene-environment interactions. Deep exploration of the clinical observations and the underlying mechanism of ketamine's antidepressant response can provide new insights into the selection of specific groups of depressed patients for ketamine treatment and to aid in monitoring the therapeutic effect during antidepressant medication. Further, targeting persistent inflammation in patients with TRD and the key molecules mediating ketamine's antidepressant effect may encourage the development of novel therapeutic strategies. FAU - Cui, Wenyan AU - Cui W AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China. cuiwy@zju.edu.cn. FAU - Ning, Yuping AU - Ning Y AD - The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Hong, Wu AU - Hong W AD - Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Ju AU - Wang J AD - School of Biomedical Engineering, Tianjin Medical University, Tianjin, China. FAU - Liu, Zhening AU - Liu Z AD - The Second Xiangya Hospital of Central South University, Changsha, China. FAU - Li, Ming D AU - Li MD AUID- ORCID: 0000-0002-5594-985X AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China. ml2km@zju.edu.cn. AD - Research Center for Air Pollution and Health, Zhejiang University, Hangzhou, China. ml2km@zju.edu.cn. AD - Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ, USA. ml2km@zju.edu.cn. LA - eng PT - Journal Article PT - Review DEP - 20180823 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Antidepressive Agents) RN - 0 (Biomarkers) RN - 3KX376GY7L (Glutamic Acid) RN - 690G0D6V8H (Ketamine) MH - Animals MH - Antidepressive Agents/pharmacology/*therapeutic use MH - Biomarkers/*metabolism MH - Depression/*drug therapy MH - Glutamic Acid/*metabolism MH - Humans MH - Inflammation/*pathology MH - Ketamine/pharmacology/*therapeutic use MH - *Signal Transduction OTO - NOTNLM OT - Biomarkers OT - Depression OT - Inflammation OT - Major depressive disorder OT - Treatment-resistant depression EDAT- 2018/08/25 06:00 MHDA- 2019/08/14 06:00 CRDT- 2018/08/25 06:00 PHST- 2018/04/17 00:00 [received] PHST- 2018/08/07 00:00 [accepted] PHST- 2018/08/25 06:00 [pubmed] PHST- 2019/08/14 06:00 [medline] PHST- 2018/08/25 06:00 [entrez] AID - 10.1007/s12035-018-1306-3 [pii] AID - 10.1007/s12035-018-1306-3 [doi] PST - ppublish SO - Mol Neurobiol. 2019 May;56(5):3484-3500. doi: 10.1007/s12035-018-1306-3. Epub 2018 Aug 23.