PMID- 31771861
OWN - NLM
STAT- MEDLINE
DCOM- 20210106
LR  - 20210915
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Linking)
VI  - 87
IP  - 3
DP  - 2020 Feb 1
TI  - Hippocampal Pathology in Clinical High-Risk Patients and the Onset of 
      Schizophrenia.
PG  - 234-242
LID - S0006-3223(19)31747-0 [pii]
LID - 10.1016/j.biopsych.2019.09.022 [doi]
AB  - BACKGROUND: We examined neuroimaging-derived hippocampal biomarkers in subjects 
      at clinical high risk (CHR) for psychosis to further characterize the 
      pathophysiology of early psychosis. We hypothesized that glutamate hyperactivity, 
      reflected by increased metabolic activity derived from functional magnetic 
      resonance imaging in the CA1 hippocampal subregion and from proton magnetic 
      resonance spectroscopy-derived hippocampal levels of glutamate/glutamine, 
      represents early hippocampal dysfunction in CHR subjects and is predictive of 
      conversion to syndromal psychosis. METHODS: We enrolled 75 CHR individuals with 
      attenuated positive symptom psychosis-risk syndrome as defined by the Structured 
      Interview for Psychosis-risk Syndromes. We used optimized magnetic resonance 
      imaging techniques to measure 3 validated in vivo pathologies of hippocampal 
      dysfunction-focal cerebral blood volume, focal atrophy, and evidence of elevated 
      glutamate concentrations. All patients were imaged at baseline and were followed 
      for up to 2 years to assess for conversion to psychosis. RESULTS: At baseline, 
      compared with control subjects, CHR individuals had high glutamate/glutamine and 
      elevated focal cerebral blood volume on functional magnetic resonance imaging, 
      but only baseline focal hippocampal atrophy predicted progression to syndromal 
      psychosis. CONCLUSIONS: These findings provide evidence that CHR patients with 
      attenuated psychotic symptoms have glutamatergic abnormalities, although only CHR 
      patients who develop syndromal psychosis exhibit focal hippocampal atrophy. 
      Furthermore, these results support the growing evidence that hippocampal 
      dysfunction is an early feature of schizophrenia and related psychotic disorders.
CI  - Copyright (c) 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All 
      rights reserved.
FAU - Provenzano, Frank A
AU  - Provenzano FA
AD  - Department of Neurology, Columbia University, New York, New York.
FAU - Guo, Jia
AU  - Guo J
AD  - Department of Psychiatry, Columbia University, New York, New York.
FAU - Wall, Melanie M
AU  - Wall MM
AD  - Department of Biostatistics, Mailman School of Public Health, Columbia 
      University, New York, New York.
FAU - Feng, Xinyang
AU  - Feng X
AD  - Department of Neurology, Columbia University, New York, New York; Department of 
      Biomedical Engineering, Columbia University, New York, New York.
FAU - Sigmon, Hannah C
AU  - Sigmon HC
AD  - University of Virginia School of Medicine, Charlottesville, Virginia.
FAU - Brucato, Gary
AU  - Brucato G
AD  - Department of Psychiatry, Columbia University, New York, New York; New York State 
      Psychiatric Institute, New York, New York.
FAU - First, Michael B
AU  - First MB
AD  - New York State Psychiatric Institute, New York, New York.
FAU - Rothman, Douglas L
AU  - Rothman DL
AD  - Department of Radiology and Biomedical Imaging, Yale University, New Haven, 
      Connecticut; Department of Biomedical Engineering, Yale University, New Haven, 
      Connecticut.
FAU - Girgis, Ragy R
AU  - Girgis RR
AD  - Department of Psychiatry, Columbia University, New York, New York; New York State 
      Psychiatric Institute, New York, New York.
FAU - Lieberman, Jeffrey A
AU  - Lieberman JA
AD  - Department of Psychiatry, Columbia University, New York, New York; New York State 
      Psychiatric Institute, New York, New York. Electronic address: 
      Jeffrey.Lieberman@nyspi.columbia.edu.
FAU - Small, Scott A
AU  - Small SA
AD  - Department of Neurology, Columbia University, New York, New York. Electronic 
      address: sas68@columbia.edu.
LA  - eng
GR  - R01 MH109159/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191003
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
CIN - Biol Psychiatry. 2020 Feb 1;87(3):200-201. PMID: 31908287
MH  - Glutamic Acid
MH  - Hippocampus/diagnostic imaging
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - *Psychotic Disorders/diagnostic imaging
MH  - *Schizophrenia/diagnostic imaging
OTO - NOTNLM
OT  - APSS
OT  - Clinical high risk
OT  - Glutamate
OT  - Neuroimaging
OT  - Schizophrenia
OT  - Volumetrics
EDAT- 2019/11/28 06:00
MHDA- 2021/01/07 06:00
CRDT- 2019/11/28 06:00
PHST- 2019/04/01 00:00 [received]
PHST- 2019/08/29 00:00 [revised]
PHST- 2019/09/02 00:00 [accepted]
PHST- 2019/11/28 06:00 [pubmed]
PHST- 2021/01/07 06:00 [medline]
PHST- 2019/11/28 06:00 [entrez]
AID - S0006-3223(19)31747-0 [pii]
AID - 10.1016/j.biopsych.2019.09.022 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2020 Feb 1;87(3):234-242. doi: 10.1016/j.biopsych.2019.09.022. 
      Epub 2019 Oct 3.