PMID- 37406595
OWN - NLM
STAT- MEDLINE
DCOM- 20230918
LR  - 20231002
IS  - 2213-1582 (Electronic)
IS  - 2213-1582 (Linking)
VI  - 39
DP  - 2023
TI  - Meta-analytic evidence of elevated choline, reduced N-acetylaspartate, and normal 
      creatine in schizophrenia and their moderation by measurement quality, echo time, 
      and medication status.
PG  - 103461
LID - S2213-1582(23)00150-X [pii]
LID - 10.1016/j.nicl.2023.103461 [doi]
LID - 103461
AB  - BACKGROUND: Brain metabolite abnormalities measured with magnetic resonance 
      spectroscopy (MRS) provide insight into pathological processes in schizophrenia. 
      Prior meta-analyses have not yet answered important questions about the influence 
      of clinical and technical factors on neurometabolite abnormalities and brain 
      region differences. To address these gaps, we performed an updated meta-analysis 
      of N-acetylaspartate (NAA), choline, and creatine levels in patients with 
      schizophrenia and assessed the moderating effects of medication status, echo 
      time, measurement quality, and other factors. METHODS: We searched citations from 
      three earlier meta-analyses and the PubMed database after the most recent 
      meta-analysis to identify studies for screening. In total, 113 publications 
      reporting 366 regional metabolite datasets met our inclusion criteria and 
      reported findings in medial prefrontal cortex (MPFC), dorsolateral prefrontal 
      cortex, frontal white matter, hippocampus, thalamus, and basal ganglia from a 
      total of 4445 patient and 3944 control observations. RESULTS: Patients with 
      schizophrenia had reduced NAA in five of the six brain regions, with a 
      statistically significant sparing of the basal ganglia. Patients had elevated 
      choline in the basal ganglia and both prefrontal cortical regions. Patient 
      creatine levels were normal in all six regions. In some regions, the NAA and 
      choline differences were greater in studies enrolling predominantly medicated 
      patients compared to studies enrolling predominantly unmedicated patients. 
      Patient NAA levels were more reduced in hippocampus and frontal white matter in 
      studies using longer echo times than those using shorter echo times. MPFC choline 
      and NAA abnormalities were greater in studies reporting better metabolite 
      measurement quality. CONCLUSIONS: Choline is elevated in the basal ganglia and 
      prefrontal cortical regions, suggesting regionally increased membrane turnover or 
      glial activation in schizophrenia. The basal ganglia are significantly spared 
      from the well-established widespread reduction of NAA in schizophrenia suggesting 
      a regional difference in disease-associated factors affecting NAA. The echo time 
      findings agree with prior reports and suggest microstructural changes cause 
      faster NAA T2 relaxation in hippocampus and frontal white matter in 
      schizophrenia. Separating the effects of medication status and illness chronicity 
      on NAA and choline abnormalities will require further patient-level studies. 
      Metabolite measurement quality was shown to be a critical factor in MRS studies 
      of schizophrenia.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Yang, Yvonne S
AU  - Yang YS
AD  - VISN22 Mental Illness Research, Education and Clinical Center, VA Greater Los 
      Angeles Healthcare System, 11301 Wilshire Blvd, Los Angeles, CA 90073, USA; 
      Department of Psychiatry and Biobehavioral Sciences, University of California, 
      Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA. Electronic address: 
      ysyang@mednet.ucla.edu.
FAU - Smucny, Jason
AU  - Smucny J
AD  - Imaging Research Center, University of California, Davis, 4701 X Street, 
      Sacramento, CA 95817, USA; Department of Psychiatry and Biobehavioral Sciences, 
      University of California, Davis, 2230 Stockton Blvd, Sacramento, CA 95817, USA.
FAU - Zhang, Huailin
AU  - Zhang H
AD  - Department of Internal Medicine, Adventist Health White Memorial, 1720 E Cesar E 
      Chavez Ave, Los Angeles, CA 90033, USA.
FAU - Maddock, Richard J
AU  - Maddock RJ
AD  - Imaging Research Center, University of California, Davis, 4701 X Street, 
      Sacramento, CA 95817, USA; Department of Psychiatry and Biobehavioral Sciences, 
      University of California, Davis, 2230 Stockton Blvd, Sacramento, CA 95817, USA. 
      Electronic address: rjmaddock@ucdavis.edu.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
DEP - 20230627
PL  - Netherlands
TA  - Neuroimage Clin
JT  - NeuroImage. Clinical
JID - 101597070
RN  - MU72812GK0 (Creatine)
RN  - N91BDP6H0X (Choline)
RN  - 997-55-7 (N-acetylaspartate)
RN  - 30KYC7MIAI (Aspartic Acid)
SB  - IM
MH  - Humans
MH  - Creatine/metabolism
MH  - *Schizophrenia/diagnosis
MH  - Choline/metabolism
MH  - Magnetic Resonance Spectroscopy
MH  - Aspartic Acid
MH  - *Brain Diseases
PMC - PMC10509531
OTO - NOTNLM
OT  - Echo time
OT  - MRS
OT  - Magnetic resonance spectroscopy
OT  - Measurement quality
OT  - Metabolites
OT  - Schizophrenia
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/07/06 01:08
MHDA- 2023/09/18 12:44
PMCR- 2023/06/27
CRDT- 2023/07/05 18:09
PHST- 2023/03/01 00:00 [received]
PHST- 2023/06/21 00:00 [revised]
PHST- 2023/06/22 00:00 [accepted]
PHST- 2023/09/18 12:44 [medline]
PHST- 2023/07/06 01:08 [pubmed]
PHST- 2023/07/05 18:09 [entrez]
PHST- 2023/06/27 00:00 [pmc-release]
AID - S2213-1582(23)00150-X [pii]
AID - 103461 [pii]
AID - 10.1016/j.nicl.2023.103461 [doi]
PST - ppublish
SO  - Neuroimage Clin. 2023;39:103461. doi: 10.1016/j.nicl.2023.103461. Epub 2023 Jun 
      27.