PMID- 33515249
OWN - NLM
STAT- MEDLINE
DCOM- 20220209
LR  - 20220209
IS  - 1745-1701 (Electronic)
IS  - 0586-7614 (Print)
IS  - 0586-7614 (Linking)
VI  - 47
IP  - 5
DP  - 2021 Aug 21
TI  - N-methyl-D-aspartate Receptor Antibody and White Matter Deficits in Schizophrenia 
      Treatment-Resistance.
PG  - 1463-1472
LID - 10.1093/schbul/sbab003 [doi]
AB  - Insufficient or lack of response to antipsychotic medications in some patients 
      with schizophrenia is a major challenge in psychiatry, but the underlying 
      mechanisms remain unclear. Two seemingly unrelated observations, cerebral white 
      matter and N-methyl-D-aspartate receptor (NMDAR) hypofunction, have been linked 
      to treatment-resistant schizophrenia (TRS). As NMDARs are critical to axonal 
      myelination and signal transduction, we hypothesized that NMDAR antibody (Ab), 
      when present in schizophrenia, may impair NMDAR functions and white matter 
      microstructures, contributing to TRS. In this study, 50 patients with TRS, 45 
      patients with nontreatment-resistant schizophrenia (NTRS), 53 patients with 
      schizophrenia at treatment initiation schizophrenia (TIS), and 90 healthy 
      controls were enrolled. Serum NMDAR Ab levels and white matter diffusion tensor 
      imaging fractional anisotropy (FA) were assessed. The white matter specificity 
      effects by NMDAR Ab were assessed by comparing with effects on cortical and 
      subcortical gray matter. Serum NMDAR Ab levels of the TRS were significantly 
      higher than those of the NTRS (P = .035). In patients with TRS, higher NMDAR Ab 
      levels were significantly associated with reduced whole-brain average FA (r = 
      -.37; P = .026), with the strongest effect at the genu of corpus callosum (r = 
      -.50; P = .0021, significant after correction for multiple comparisons). 
      Conversely, there was no significant correlation between whole-brain or regional 
      cortical thickness or any subcortical gray matter structural volume and NMDAR Ab 
      levels in TRS. Our finding highlights a potential NMDAR mechanism on white matter 
      microstructure impairment in schizophrenia that may contribute to their treatment 
      resistance to antipsychotic medications.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      Maryland Psychiatric Research Center. All rights reserved. For permissions, 
      please email: journals.permissions@oup.com.
FAU - Tong, Jinghui
AU  - Tong J
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Zhou, Yanfang
AU  - Zhou Y
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Huang, Junchao
AU  - Huang J
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Zhang, Ping
AU  - Zhang P
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Fan, Fengmei
AU  - Fan F
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Chen, Song
AU  - Chen S
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Tian, Baopeng
AU  - Tian B
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Cui, Yimin
AU  - Cui Y
AD  - Department of Pharmacy, Peking University First Hospital, Beijing, P. R. China.
FAU - Tian, Li
AU  - Tian L
AD  - Institute of Biomedicine and Translational Medicine, Department of Physiology, 
      Faculty of Medicine, University of Tartu, Tartu, Estonia.
FAU - Tan, Shuping
AU  - Tan S
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Wang, Zhiren
AU  - Wang Z
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Feng, Wei
AU  - Feng W
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Yang, Fude
AU  - Yang F
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Hare, Stephanie
AU  - Hare S
AD  - Maryland Psychiatric Research Center, Department of Psychiatry, University of 
      Maryland School of Medicine, Baltimore, MD, USA.
FAU - Goldwaser, Eric L
AU  - Goldwaser EL
AD  - Maryland Psychiatric Research Center, Department of Psychiatry, University of 
      Maryland School of Medicine, Baltimore, MD, USA.
FAU - Bruce, Heather A
AU  - Bruce HA
AD  - Maryland Psychiatric Research Center, Department of Psychiatry, University of 
      Maryland School of Medicine, Baltimore, MD, USA.
FAU - Kvarta, Mark
AU  - Kvarta M
AD  - Maryland Psychiatric Research Center, Department of Psychiatry, University of 
      Maryland School of Medicine, Baltimore, MD, USA.
FAU - Chen, Shuo
AU  - Chen S
AD  - Maryland Psychiatric Research Center, Department of Psychiatry, University of 
      Maryland School of Medicine, Baltimore, MD, USA.
FAU - Kochunov, Peter
AU  - Kochunov P
AD  - Maryland Psychiatric Research Center, Department of Psychiatry, University of 
      Maryland School of Medicine, Baltimore, MD, USA.
FAU - Tan, Yunlong
AU  - Tan Y
AUID- ORCID: 0000-0002-3522-3912
AD  - Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan 
      Hospital, Beijing, P. R. China.
FAU - Hong, L Elliot
AU  - Hong LE
AD  - Maryland Psychiatric Research Center, Department of Psychiatry, University of 
      Maryland School of Medicine, Baltimore, MD, USA.
LA  - eng
GR  - DP1 DA048968/DA/NIDA NIH HHS/United States
GR  - R01 EB015611/EB/NIBIB NIH HHS/United States
GR  - R01 MH116948/MH/NIMH NIH HHS/United States
GR  - S10 OD023696/OD/NIH HHS/United States
GR  - R01MH112180/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Schizophr Bull
JT  - Schizophrenia bulletin
JID - 0236760
RN  - 0 (Autoantibodies)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Adult
MH  - Autoantibodies/*blood
MH  - Cerebral Cortex/diagnostic imaging/*pathology
MH  - Corpus Callosum/diagnostic imaging/*pathology
MH  - Diffusion Tensor Imaging
MH  - Female
MH  - Gray Matter/diagnostic imaging/*pathology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Receptors, N-Methyl-D-Aspartate/*immunology
MH  - Schizophrenia, Treatment-Resistant/blood/diagnostic 
      imaging/*immunology/*pathology
MH  - White Matter/diagnostic imaging/*pathology
MH  - Young Adult
PMC - PMC8379535
OTO - NOTNLM
OT  - NMDAR antibody
OT  - cortical thickness
OT  - genu of corpus callosum
OT  - subcortical gray matter structural volume
OT  - treatment-resistant schizophrenia
OT  - white matter FA
EDAT- 2021/01/31 06:00
MHDA- 2022/02/10 06:00
PMCR- 2022/01/30
CRDT- 2021/01/30 12:05
PHST- 2021/01/31 06:00 [pubmed]
PHST- 2022/02/10 06:00 [medline]
PHST- 2021/01/30 12:05 [entrez]
PHST- 2022/01/30 00:00 [pmc-release]
AID - 6124424 [pii]
AID - sbab003 [pii]
AID - 10.1093/schbul/sbab003 [doi]
PST - ppublish
SO  - Schizophr Bull. 2021 Aug 21;47(5):1463-1472. doi: 10.1093/schbul/sbab003.