PMID- 28115738
OWN - NLM
STAT- MEDLINE
DCOM- 20171116
LR  - 20231112
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 22
IP  - 9
DP  - 2017 Sep
TI  - Glutamate imaging (GluCEST) reveals lower brain GluCEST contrast in patients on 
      the psychosis spectrum.
PG  - 1298-1305
LID - 10.1038/mp.2016.258 [doi]
AB  - Psychosis commonly develops in adolescence or early adulthood. Youths at clinical 
      high risk (CHR) for psychosis exhibit similar, subtle symptoms to those with 
      schizophrenia (SZ). Malfunctioning neurotransmitter systems, such as glutamate, 
      are implicated in the disease progression of psychosis. Yet, in vivo imaging 
      techniques for measuring glutamate across the cortex are limited. Here, we use a 
      novel 7 Tesla MRI glutamate imaging technique (GluCEST) to estimate changes in 
      glutamate levels across cortical and subcortical regions in young healthy 
      individuals and ones on the psychosis spectrum. Individuals on the psychosis 
      spectrum (PS; n=19) and healthy young individuals (HC; n=17) underwent MRI 
      imaging at 3 and 7 T. At 7 T, a single slice GluCEST technique was used to 
      estimate in vivo glutamate. GluCEST contrast was compared within and across the 
      subcortex, frontal, parietal and occipital lobes. Subcortical (chi(2) (1)=4.65, 
      P=0.031) and lobular (chi(2) (1)=5.17, P=0.023) GluCEST contrast levels were lower 
      in PS compared with HC. Abnormal GluCEST contrast levels were evident in both CHR 
      (n=14) and SZ (n=5) subjects, and correlated differentially, across regions, with 
      clinical symptoms. Our findings describe a pattern of abnormal brain 
      neurochemistry early in the course of psychosis. Specifically, CHR and young SZ 
      exhibit diffuse abnormalities in GluCEST contrast attributable to a major 
      contribution from glutamate. We suggest that neurochemical profiles of GluCEST 
      contrast across cortex and subcortex may be considered markers of early 
      psychosis. GluCEST methodology thus shows promise to further elucidate the 
      progression of the psychosis disease state.
FAU - Roalf, D R
AU  - Roalf DR
AD  - Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, 
      University of Pennsylvania Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Nanga, R P R
AU  - Nanga RPR
AD  - Department of Radiology &Center for Magnetic and Optical Imaging, University of 
      Pennsylvania Perelman School of Medicine, University of Pennsylvania, 
      Philadelphia, PA, USA.
FAU - Rupert, P E
AU  - Rupert PE
AD  - Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, 
      University of Pennsylvania Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Hariharan, H
AU  - Hariharan H
AD  - Department of Radiology &Center for Magnetic and Optical Imaging, University of 
      Pennsylvania Perelman School of Medicine, University of Pennsylvania, 
      Philadelphia, PA, USA.
FAU - Quarmley, M
AU  - Quarmley M
AD  - Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, 
      University of Pennsylvania Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Calkins, M E
AU  - Calkins ME
AD  - Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, 
      University of Pennsylvania Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Dress, E
AU  - Dress E
AD  - Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, 
      University of Pennsylvania Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Prabhakaran, K
AU  - Prabhakaran K
AD  - Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, 
      University of Pennsylvania Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Elliott, M A
AU  - Elliott MA
AD  - Department of Radiology &Center for Magnetic and Optical Imaging, University of 
      Pennsylvania Perelman School of Medicine, University of Pennsylvania, 
      Philadelphia, PA, USA.
FAU - Moberg, P J
AU  - Moberg PJ
AD  - Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, 
      University of Pennsylvania Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Gur, R C
AU  - Gur RC
AD  - Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, 
      University of Pennsylvania Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Gur, R E
AU  - Gur RE
AD  - Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, 
      University of Pennsylvania Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Reddy, R
AU  - Reddy R
AD  - Department of Radiology &Center for Magnetic and Optical Imaging, University of 
      Pennsylvania Perelman School of Medicine, University of Pennsylvania, 
      Philadelphia, PA, USA.
FAU - Turetsky, B I
AU  - Turetsky BI
AD  - Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, 
      University of Pennsylvania Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, USA.
LA  - eng
GR  - P50 MH096891/MH/NIMH NIH HHS/United States
GR  - T32 MH019112/MH/NIMH NIH HHS/United States
GR  - R01 MH099156/MH/NIMH NIH HHS/United States
GR  - P41 EB015893/EB/NIBIB NIH HHS/United States
GR  - R01 NS087516/NS/NINDS NIH HHS/United States
GR  - K01 MH102609/MH/NIMH NIH HHS/United States
GR  - RC2 MH089983/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 - 20170124
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Adolescent
MH  - Brain/diagnostic imaging
MH  - Female
MH  - Glutamic Acid/*analysis
MH  - Humans
MH  - Magnetic Resonance Imaging/*methods
MH  - Male
MH  - Psychotic Disorders/*diagnostic imaging
MH  - Risk Factors
MH  - Schizophrenia
PMC - PMC5822706
MID - NIHMS834848
COIS- CONFLICT OF INTERESTS: The authors declare no competing financial interests.
EDAT- 2017/01/25 06:00
MHDA- 2017/11/29 06:00
PMCR- 2018/02/22
CRDT- 2017/01/25 06:00
PHST- 2016/02/19 00:00 [received]
PHST- 2016/10/19 00:00 [revised]
PHST- 2016/12/06 00:00 [accepted]
PHST- 2017/01/25 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/01/25 06:00 [entrez]
PHST- 2018/02/22 00:00 [pmc-release]
AID - mp2016258 [pii]
AID - 10.1038/mp.2016.258 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2017 Sep;22(9):1298-1305. doi: 10.1038/mp.2016.258. Epub 2017 Jan 
      24.