PMID- 28375210
OWN - NLM
STAT- MEDLINE
DCOM- 20171219
LR  - 20220129
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 7
IP  - 4
DP  - 2017 Apr 4
TI  - Corticolimbic hyper-response to emotion and glutamatergic function in people with 
      high schizotypy: a multimodal fMRI-MRS study.
PG  - e1083
LID - 10.1038/tp.2017.53 [doi]
AB  - Animal models and human neuroimaging studies suggest that altered levels of 
      glutamatergic metabolites within a corticolimbic circuit have a major role in the 
      pathophysiology of schizophrenia. Rodent models propose that prefrontal glutamate 
      dysfunction could lead to amygdala hyper-response to environmental stress and 
      underlie hippocampal overdrive in schizophrenia. Here we determine whether 
      changes in brain glutamate are present in individuals with high schizotypy (HS), 
      which refers to the presence of schizophrenia-like characteristics in healthy 
      individuals, and whether glutamate levels are related to altered corticolimbic 
      response to emotion. Twenty-one healthy HS subjects and 22 healthy subjects with 
      low schizotypy (LS) were selected based on their Oxford and Liverpool Inventory 
      of Feelings and Experiences rating. Glutamate levels were measured in the 
      anterior cingulate cortex (ACC) using proton magnetic resonance spectroscopy, 
      followed by a functional magnetic resonance imaging (fMRI) scan to measure 
      corticolimbic response during emotional processing. fMRI results and fMRI x 
      glutamate interactions were considered significant after voxel-wise P<0.05 
      family-wise error correction. While viewing emotional pictures, HS individuals 
      showed greater activation than did subjects with LS in the caudate, and 
      marginally in the ACC, hippocampus, medial prefrontal cortex (MPFC) and putamen. 
      Although no between-group differences were found in glutamate concentrations, 
      within the HS group ACC glutamate was negatively correlated with striatal 
      activation (left: z=4.30, P=0.004 and right: z=4.12 P=0.008 caudate; left 
      putamen: z=3.89, P=0.018) and marginally with MPFC (z=3.55, P=0.052) and amygdala 
      (left: z=2.88, P=0.062; right: z=2.79, P=0.079), correlations that were not 
      present in LS subjects. These findings provide, to our knowledge, the first 
      evidence that brain glutamate levels are associated with hyper-responsivity in 
      brain regions thought to be critical in the pathophysiology of psychosis.
FAU - Modinos, G
AU  - Modinos G
AD  - Institute of Psychiatry, Psychology and Neuroscience, King's College London, 
      London, UK.
FAU - McLaughlin, A
AU  - McLaughlin A
AD  - Institute of Psychiatry, Psychology and Neuroscience, King's College London, 
      London, UK.
FAU - Egerton, A
AU  - Egerton A
AD  - Institute of Psychiatry, Psychology and Neuroscience, King's College London, 
      London, UK.
FAU - McMullen, K
AU  - McMullen K
AD  - Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
FAU - Kumari, V
AU  - Kumari V
AD  - Institute of Psychiatry, Psychology and Neuroscience, King's College London, 
      London, UK.
FAU - Barker, G J
AU  - Barker GJ
AD  - Institute of Psychiatry, Psychology and Neuroscience, King's College London, 
      London, UK.
FAU - Keysers, C
AU  - Keysers C
AUID- ORCID: 0000-0002-2845-5467
AD  - Social Brain Laboratory, Netherlands Institute for Neuroscience, Netherlands 
      Academy for Arts and Sciences (KNAW), Amsterdam, The Netherlands.
AD  - Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.
FAU - Williams, S C R
AU  - Williams SC
AD  - Institute of Psychiatry, Psychology and Neuroscience, King's College London, 
      London, UK.
LA  - eng
GR  - 202397/Z/16/Z/Wellcome Trust/United Kingdom
GR  - MR/L003988/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/N026063/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170404
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Brain/diagnostic imaging/metabolism
MH  - Cerebral Cortex/*diagnostic imaging/metabolism/physiology
MH  - Emotions/*physiology
MH  - Female
MH  - Glutamic Acid/*metabolism
MH  - Gyrus Cinguli/diagnostic imaging/metabolism
MH  - Hippocampus/diagnostic imaging/metabolism
MH  - Humans
MH  - Limbic System/*diagnostic imaging/metabolism/physiology
MH  - Magnetic Resonance Imaging/*methods
MH  - Magnetic Resonance Spectroscopy/*methods
MH  - Male
MH  - Middle Aged
MH  - Models, Animal
MH  - Multimodal Imaging/*methods
MH  - Neuroimaging/methods
MH  - Prefrontal Cortex/metabolism
MH  - Psychotic Disorders/diagnostic imaging/metabolism/physiopathology
MH  - Schizophrenia/diagnostic imaging/metabolism/physiopathology
MH  - Schizotypal Personality Disorder/*diagnostic imaging/metabolism/physiopathology
MH  - Young Adult
PMC - PMC5416694
COIS- The authors declare no conflict of interest.
EDAT- 2017/04/05 06:00
MHDA- 2017/12/20 06:00
PMCR- 2017/04/01
CRDT- 2017/04/05 06:00
PHST- 2016/11/05 00:00 [received]
PHST- 2016/12/15 00:00 [revised]
PHST- 2017/02/01 00:00 [accepted]
PHST- 2017/04/05 06:00 [entrez]
PHST- 2017/04/05 06:00 [pubmed]
PHST- 2017/12/20 06:00 [medline]
PHST- 2017/04/01 00:00 [pmc-release]
AID - tp201753 [pii]
AID - 10.1038/tp.2017.53 [doi]
PST - epublish
SO  - Transl Psychiatry. 2017 Apr 4;7(4):e1083. doi: 10.1038/tp.2017.53.