TY - JOUR
T1 - Cerebral glutamate and GABA levels in high-risk of psychosis states
T2 - A focused review and meta-analysis of 1H-MRS studies
AU - Wenneberg, Christina
AU - Glenthøj, Birte Yding
AU - Hjorthøj, Carsten
AU - Buchardt Zingenberg, Frederik Johan
AU - Glenthøj, Louise Birkedal
AU - Rostrup, Egill
AU - Broberg, Brian Villumsen
AU - Nordentoft, Merete
N1 - Copyright © 2019 Elsevier B.V. All rights reserved.
PY - 2020/1
Y1 - 2020/1
N2 - Disturbances in the brain glutamate and GABA (γ-aminobutyric acid) homeostasis may be markers of transition to psychosis in individuals at high-risk (HR). Knowledge of GABA and glutamate levels in HR stages could give an insight into changes in the neurochemistry underlying psychosis. Studies on glutamate in HR have provided conflicting data, and GABA studies have only recently been initialized. In this meta-analysis, we compared cerebral levels of glutamate and GABA in HR individuals with healthy controls (HC). We searched Medline and Embase for articles published on 1H-MRS studies on glutamate and GABA in HR states until April 9th, 2019. We identified a total of 28 eligible studies, of which eight reported GABA (243 HR, 356 HC) and 26 reported glutamate (299 HR, 279 HC) or Glx (glutamate + glutamine) (584 HR, 632 HC) levels. Sample sizes varied from 6 to 75 for HR and 10 to 184 for HC. Our meta-analysis of 1H-MRS studies on glutamate and GABA in HR states displayed significantly lower (P = 0.0003) levels of thalamic glutamate in HR individuals than in HC and significantly higher (P = 0.001) Glx in the frontal lobe of genetic HR individuals (1st-degree relatives) than in HC. No other significant differences in glutamate and GABA levels were found. Subject numbers in the studies on glutamate as well as GABA levels were generally small and the data conflicting. Our meta-analytical findings highlight the need for larger and more homogeneous studies of glutamate and GABA in high-risk states.
AB - Disturbances in the brain glutamate and GABA (γ-aminobutyric acid) homeostasis may be markers of transition to psychosis in individuals at high-risk (HR). Knowledge of GABA and glutamate levels in HR stages could give an insight into changes in the neurochemistry underlying psychosis. Studies on glutamate in HR have provided conflicting data, and GABA studies have only recently been initialized. In this meta-analysis, we compared cerebral levels of glutamate and GABA in HR individuals with healthy controls (HC). We searched Medline and Embase for articles published on 1H-MRS studies on glutamate and GABA in HR states until April 9th, 2019. We identified a total of 28 eligible studies, of which eight reported GABA (243 HR, 356 HC) and 26 reported glutamate (299 HR, 279 HC) or Glx (glutamate + glutamine) (584 HR, 632 HC) levels. Sample sizes varied from 6 to 75 for HR and 10 to 184 for HC. Our meta-analysis of 1H-MRS studies on glutamate and GABA in HR states displayed significantly lower (P = 0.0003) levels of thalamic glutamate in HR individuals than in HC and significantly higher (P = 0.001) Glx in the frontal lobe of genetic HR individuals (1st-degree relatives) than in HC. No other significant differences in glutamate and GABA levels were found. Subject numbers in the studies on glutamate as well as GABA levels were generally small and the data conflicting. Our meta-analytical findings highlight the need for larger and more homogeneous studies of glutamate and GABA in high-risk states.
KW - Frontal Lobe/diagnostic imaging
KW - Glutamic Acid/metabolism
KW - Humans
KW - Prodromal Symptoms
KW - Proton Magnetic Resonance Spectroscopy
KW - Psychotic Disorders/diagnostic imaging
KW - Risk
KW - Thalamus/diagnostic imaging
KW - gamma-Aminobutyric Acid/metabolism
KW - Glutamate
KW - 1H-MRS
KW - GABA
KW - UHR
KW - High-risk
KW - Prodromal
U2 - 10.1016/j.schres.2019.10.050
DO - 10.1016/j.schres.2019.10.050
M3 - Review
C2 - 31784336
VL - 215
SP - 38
EP - 48
JO - Schizophrenia Research
JF - Schizophrenia Research
SN - 0920-9964
M1 - 215
ER -