PMID- 26013316
OWN - NLM
STAT- MEDLINE
DCOM- 20170110
LR  - 20201125
IS  - 1440-1614 (Electronic)
IS  - 0004-8674 (Print)
IS  - 0004-8674 (Linking)
VI  - 50
IP  - 3
DP  - 2016 Mar
TI  - Changes in cortical N-methyl-D-aspartate receptors and post-synaptic density 
      protein 95 in schizophrenia, mood disorders and suicide.
PG  - 275-83
LID - 10.1177/0004867415586601 [doi]
AB  - OBJECTIVES: In humans, depending on dose, blocking the N-methyl-D-aspartate 
      receptor (NMDAR) with ketamine can cause psychomimetic or antidepressant effects. 
      The overall outcome for drugs such as ketamine depends on dose and the number of 
      its available binding sites in the central nervous system, and to understand 
      something of the latter variable we measure NMDAR in the frontal pole, 
      dorsolateral prefrontal, anterior cingulate and parietal cortices from people 
      with schizophrenia, bipolar disorder, major depressive disorders and age/sex 
      matched controls. METHOD: We measured levels of NMDARs (using [(3)H]MK-801 
      binding) and NMDAR sub-unit mRNAs (GRINs: using in situ hybridisation) as well as 
      post-synaptic density protein 95 (anterior cingulate cortex only; not major 
      depressive disorders: an NMDAR post-synaptic associated protein) in bipolar 
      disorder, schizophrenia and controls. RESULTS: Compared to controls, levels of 
      NMDAR were lower in the outer laminae of the dorsolateral prefrontal cortex 
      (-17%, p = 0.01) in people with schizophrenia. In bipolar disorder, levels of 
      NMDAR binding (laminae IV-VI; -19%, p < 0.01) and GRIN2C mRNA (laminae I-VI; 
      -27%, p < 0.05) were lower in the anterior cingulate cortex and NMDAR binding was 
      lower in the outer lamina IV of the dorsolateral prefrontal cortex (-19%, 
      p < 0.01). In major depressive disorders, levels of GRIN2D mRNA were higher in 
      frontal pole (+22%, p < 0.05). In suicide completers, levels of GRIN2B mRNA were 
      higher in parietal cortex (+20%, p < 0.01) but lower (-35%, p = 0.02) in 
      dorsolateral prefrontal cortex while post-synaptic density protein 95 was higher 
      (+26%, p < 0.05) in anterior cingulate cortex. CONCLUSION: These data suggest 
      that differences in cortical NMDAR expression and post-synaptic density protein 
      95 are present in psychiatric disorders and suicide completion and may contribute 
      to different responses to ketamine.
CI  - (c) The Royal Australian and New Zealand College of Psychiatrists 2015.
FAU - Dean, Brian
AU  - Dean B
AD  - Molecular Psychiatry Laboratory, The Florey Institute for Neuroscience and Mental 
      Health, Parkville, VIC, Australia Psychiatric Neuropathology Laboratory, 
      Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia 
      brian.dean@florey.edu.au.
FAU - Gibbons, Andrew S
AU  - Gibbons AS
AD  - Molecular Psychiatry Laboratory, The Florey Institute for Neuroscience and Mental 
      Health, Parkville, VIC, Australia Psychiatric Neuropathology Laboratory, 
      Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.
FAU - Boer, Simone
AU  - Boer S
AD  - Molecular Psychiatry Laboratory, The Florey Institute for Neuroscience and Mental 
      Health, Parkville, VIC, Australia.
FAU - Uezato, Akihito
AU  - Uezato A
AD  - Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental 
      University, Tokyo, Japan.
FAU - Meador-Woodruff, James
AU  - Meador-Woodruff J
AD  - Department of Psychiatry, University of Alabama Birmingham, Birmingham, AL, USA.
FAU - Scarr, Elizabeth
AU  - Scarr E
AD  - Molecular Psychiatry Laboratory, The Florey Institute for Neuroscience and Mental 
      Health, Parkville, VIC, Australia Psychiatric Neuropathology Laboratory, 
      Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.
FAU - McCullumsmith, Robert E
AU  - McCullumsmith RE
AD  - Department of Psychiatry, University of Cincinnati, Cincinnati, OH, USA.
LA  - eng
GR  - R01 MH094445/MH/NIMH NIH HHS/United States
GR  - R01 MH107487/MH/NIMH NIH HHS/United States
GR  - R21 MH107916/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150526
PL  - England
TA  - Aust N Z J Psychiatry
JT  - The Australian and New Zealand journal of psychiatry
JID - 0111052
RN  - 0 (Biomarkers)
RN  - 0 (DLG4 protein, human)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Adult
MH  - Biomarkers
MH  - Bipolar Disorder/drug therapy/*genetics
MH  - Depressive Disorder, Major/drug therapy/*genetics
MH  - Disks Large Homolog 4 Protein
MH  - Female
MH  - Gyrus Cinguli/metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*genetics
MH  - Ketamine/*therapeutic use
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - Middle Aged
MH  - Prefrontal Cortex/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*genetics
MH  - Schizophrenia/drug therapy/*genetics
MH  - Suicide
PMC - PMC7683009
MID - NIHMS1583387
OTO - NOTNLM
OT  - NMDA
OT  - Schizophrenia
OT  - bipolar disorders
OT  - cortex
OT  - major depressive disorders
COIS- Declaration of interest None of the authors have any conflict of interest, and 
      the research described in this manuscript was completed in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest. E.S. has previously received honorarium from Astra-Zeneca 
      and travel support from GSK that were unrelated to this research.
EDAT- 2015/05/28 06:00
MHDA- 2017/01/11 06:00
PMCR- 2020/11/23
CRDT- 2015/05/28 06:00
PHST- 2015/05/28 06:00 [entrez]
PHST- 2015/05/28 06:00 [pubmed]
PHST- 2017/01/11 06:00 [medline]
PHST- 2020/11/23 00:00 [pmc-release]
AID - 0004867415586601 [pii]
AID - 10.1177/0004867415586601 [doi]
PST - ppublish
SO  - Aust N Z J Psychiatry. 2016 Mar;50(3):275-83. doi: 10.1177/0004867415586601. Epub 
      2015 May 26.