PMID- 34163013
OWN - NLM
STAT- MEDLINE
DCOM- 20220405
LR  - 20230205
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 27
IP  - 1
DP  - 2022 Jan
TI  - Aberrant maturation and connectivity of prefrontal cortex in 
      schizophrenia-contribution of NMDA receptor development and hypofunction.
PG  - 731-743
LID - 10.1038/s41380-021-01196-w [doi]
AB  - The neurobiology of schizophrenia involves multiple facets of pathophysiology, 
      ranging from its genetic basis over changes in neurochemistry and 
      neurophysiology, to the systemic level of neural circuits. Although the precise 
      mechanisms associated with the neuropathophysiology remain elusive, one essential 
      aspect is the aberrant maturation and connectivity of the prefrontal cortex that 
      leads to complex symptoms in various stages of the disease. Here, we focus on how 
      early developmental dysfunction, especially N-methyl-D-aspartate receptor (NMDAR) 
      development and hypofunction, may lead to the dysfunction of both local circuitry 
      within the prefrontal cortex and its long-range connectivity. More specifically, 
      we will focus on an "all roads lead to Rome" hypothesis, i.e., how NMDAR 
      hypofunction during development acts as a convergence point and leads to local 
      gamma-aminobutyric acid (GABA) deficits and input-output dysconnectivity in the 
      prefrontal cortex, which eventually induce cognitive and social deficits. Many 
      outstanding questions and hypothetical mechanisms are listed for future 
      investigations of this intriguing hypothesis that may lead to a better 
      understanding of the aberrant maturation and connectivity associated with the 
      prefrontal cortex.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature Limited.
FAU - Gao, Wen-Jun
AU  - Gao WJ
AUID- ORCID: 0000-0002-8585-3082
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 
      Philadelphia, PA, 19129, USA. wg38@drexel.edu.
FAU - Yang, Sha-Sha
AU  - Yang SS
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 
      Philadelphia, PA, 19129, USA.
FAU - Mack, Nancy R
AU  - Mack NR
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 
      Philadelphia, PA, 19129, USA.
FAU - Chamberlin, Linda A
AU  - Chamberlin LA
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 
      Philadelphia, PA, 19129, USA.
LA  - eng
GR  - R21 MH121836/MH/NIMH NIH HHS/United States
GR  - R21 MH097623/MH/NIMH NIH HHS/United States
GR  - R01 MH085666/MH/NIMH NIH HHS/United States
GR  - R21 MH129989/MH/NIMH NIH HHS/United States
GR  - R21 MH079117/MH/NIMH NIH HHS/United States
GR  - R21 MH111609/MH/NIMH NIH HHS/United States
GR  - R21 MH110678/MH/NIMH NIH HHS/United States
GR  - P50 MH068789/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
DEP - 20210623
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Humans
MH  - Prefrontal Cortex/metabolism
MH  - *Receptors, N-Methyl-D-Aspartate/metabolism
MH  - *Schizophrenia/genetics
MH  - Signal Transduction
PMC - PMC8695640
MID - NIHMS1714156
COIS- Conflict of Interest The authors declare no competing financial interests.
EDAT- 2021/06/25 06:00
MHDA- 2022/04/05 06:00
PMCR- 2022/03/31
CRDT- 2021/06/24 06:24
PHST- 2020/10/24 00:00 [received]
PHST- 2021/06/10 00:00 [accepted]
PHST- 2021/06/02 00:00 [revised]
PHST- 2021/06/25 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2021/06/24 06:24 [entrez]
PHST- 2022/03/31 00:00 [pmc-release]
AID - 10.1038/s41380-021-01196-w [pii]
AID - 10.1038/s41380-021-01196-w [doi]
PST - ppublish
SO  - Mol Psychiatry. 2022 Jan;27(1):731-743. doi: 10.1038/s41380-021-01196-w. Epub 
      2021 Jun 23.