PMID- 30699855 OWN - NLM STAT- MEDLINE DCOM- 20190403 LR - 20221207 IS - 1573-2517 (Electronic) IS - 0165-0327 (Linking) VI - 245 DP - 2019 Feb 15 TI - Altered mRNA expressions for N-methyl-D-aspartate receptor-related genes in WBC of patients with major depressive disorder. PG - 1119-1125 LID - S0165-0327(18)32783-6 [pii] LID - 10.1016/j.jad.2018.12.016 [doi] AB - OBJECTIVE: Major depressive disorder (MDD) is a complex mental disorder. The lack of well-established biomarkers hinders its diagnosis, treatment, and new-drug development. N-methyl-D-aspartate receptor (NMDAR) dysfunction has been implicated in the pathogenesis of MDD. This study examined whether expressions of the NMDAR-related genes are characteristic of MDD. METHODS: Expressions of NMDAR-related genes including SRR, SHMT2, PSAT1, GCAT, GAD1, SLC1A4, NRG1 and COMT in peripheral WBCs of 110 patients with MDD (25 drug-naive, 21 drug-free, and 64 medicated patients) and 125 healthy individuals were measured using quantitative PCR. RESULTS: The mRNA expression levels of SRR, PSAT1, GCAT, GAD1, NRG1 and COMT were significantly different among the four groups (all p < 0.05). For drug-naive patients, the DeltaDeltaCT values of SRR, PSAT1, GCAT, GAD1, and NRG1 mRNA expressions were significantly different from those in healthy individuals (all p < 0.05). The ROC analysis of the DeltaDeltaCT values of the target genes for differentiating drug-naive patients from healthy controls showed an excellent sensitivity (0.960) and modest specificity (0.640) (AUC = 0.889). Drug-free and medicated patients obtained less favorable AUC values while compared to healthy controls. The results for the age- and sex-matched cohort were similar to those of the unmatched cohort. CONCLUSIONS: This is the first study demonstrating that the peripheral mRNA expression levels of NMDAR-related genes may be altered in patients with MDD, especially drug-naive individuals. The finding supports the NMDAR hypothesis of depression. Whether mRNA expresssion of NMDAR-related genes could serve as a potential biomarker of MDD deserves further investigations. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Lin, Chieh-Hsin AU - Lin CH AD - Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. FAU - Huang, Min-Wei AU - Huang MW AD - Department of Psychiatry, Chiayi Branch, Taichung Veterans General Hospital, Chia-Yi, Taiwan. FAU - Lin, Ching-Hua AU - Lin CH AD - Department of Psychiatry, Kai-Suan Psychiatric Hospital, Kaohsiung, Taiwan. FAU - Huang, Chiung-Hsien AU - Huang CH AD - Department of Medicine Research, China Medical University Hospital, Taichung, Taiwan. FAU - Lane, Hsien-Yuan AU - Lane HY AD - Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Department of Psychiatry, Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan; Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan. Electronic address: hylane@mail.cmuh.org.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181210 PL - Netherlands TA - J Affect Disord JT - Journal of affective disorders JID - 7906073 RN - 0 (Amino Acid Transport System ASC) RN - 0 (Antidepressive Agents) RN - 0 (Biomarkers) RN - 0 (NRG1 protein, human) RN - 0 (Neuregulin-1) RN - 0 (RNA, Messenger) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (SLC1A4 protein, human) RN - EC 2.1.1.6 (COMT protein, human) RN - EC 2.1.1.6 (Catechol O-Methyltransferase) RN - EC 2.1.2.1 (Glycine Hydroxymethyltransferase) RN - EC 2.1.2.1 (SHMT protein, human) RN - EC 2.3.- (Acyltransferases) RN - EC 2.3.1.43 (Aeromonas hydrophilia lipase-acyltransferase) RN - EC 2.6.1.- (Transaminases) RN - EC 2.6.1.52 (phosphoserine aminotransferase) RN - EC 3.1.1.3 (Lipase) RN - EC 4.1.1.15 (Glutamate Decarboxylase) RN - EC 4.1.1.15 (glutamate decarboxylase 1) RN - EC 5.1.- (Racemases and Epimerases) RN - EC 5.1.1.16 (serine racemase) SB - IM MH - Acyltransferases/genetics/metabolism MH - Adult MH - Amino Acid Transport System ASC/genetics/metabolism MH - Antidepressive Agents/therapeutic use MH - Asian People/genetics MH - Biomarkers/metabolism MH - Case-Control Studies MH - Catechol O-Methyltransferase/genetics/metabolism MH - Cohort Studies MH - Depressive Disorder, Major/drug therapy/*genetics/metabolism MH - Female MH - Glutamate Decarboxylase/genetics/metabolism MH - Glycine Hydroxymethyltransferase/genetics/metabolism MH - Humans MH - Leukocytes/*metabolism MH - Lipase/genetics/metabolism MH - Male MH - Middle Aged MH - Neuregulin-1/genetics/metabolism MH - RNA, Messenger/*metabolism MH - ROC Curve MH - Racemases and Epimerases/genetics/metabolism MH - Receptors, N-Methyl-D-Aspartate/*metabolism MH - Transaminases/genetics/metabolism OTO - NOTNLM OT - Gene expression OT - Major depressive disorder OT - N-methyl-D-aspartate receptor EDAT- 2019/02/01 06:00 MHDA- 2019/04/04 06:00 CRDT- 2019/02/01 06:00 PHST- 2018/10/31 00:00 [received] PHST- 2018/11/27 00:00 [revised] PHST- 2018/12/08 00:00 [accepted] PHST- 2019/02/01 06:00 [entrez] PHST- 2019/02/01 06:00 [pubmed] PHST- 2019/04/04 06:00 [medline] AID - S0165-0327(18)32783-6 [pii] AID - 10.1016/j.jad.2018.12.016 [doi] PST - ppublish SO - J Affect Disord. 2019 Feb 15;245:1119-1125. doi: 10.1016/j.jad.2018.12.016. Epub 2018 Dec 10.