Scientific article

Excitatory/Inhibitory Imbalance Underlies Hippocampal Atrophy in Individuals With 22q11.2 Deletion Syndrome With Psychotic Symptoms

First online date2023-04-01

Background: Abnormal neurotransmitter levels have been reported in individuals at high risk for schizophrenia, leading to a shift in the excitatory/inhibitory balance. However, it is unclear whether these alterations predate the onset of clinically relevant symptoms. Our aim was to explore in vivo measures of excitatory/inhibitory balance in 22q11.2 deletion carriers, a population at genetic risk for psychosis.

Methods: Glx (glutamate+glutamine) and GABA+ (gamma-aminobutyric acid with macromolecules and homocarnosine) concentrations were estimated in the anterior cingulate cortex, superior temporal cortex, and hippocampus using the Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence and the Gannet toolbox in 52 deletion carriers and 42 control participants. T1-weighted images were acquired longitudinally and processed with FreeSurfer version 6 to extract hippocampal volume. Subgroup analyses were conducted in deletion carriers with psychotic symptoms.

Results: While no differences were found in the anterior cingulate cortex, deletion carriers had higher levels of Glx in the hippocampus and superior temporal cortex and lower levels of GABA+ in the hippocampus than control participants. We additionally found a higher Glx concentration in the hippocampus of deletion carriers with psychotic symptoms. Finally, more pronounced hippocampal atrophy was significantly associated with increased Glx levels in deletion carriers.

Conclusions: We provide evidence for an excitatory/inhibitory imbalance in temporal brain structures of deletion carriers, with a further hippocampal Glx increase in individuals with psychotic symptoms that was associated with hippocampal atrophy. These results are in line with theories proposing abnormally enhanced glutamate levels as a mechanistic explanation for hippocampal atrophy via excitotoxicity. Our results highlight a central role of glutamate in the hippocampus of individuals at genetic risk for schizophrenia.

  • Development
  • GABA
  • Glutamate
  • Hippocampus
  • MRS
  • Schizophrenia
Citation (ISO format)
MANCINI, Valentina et al. Excitatory/Inhibitory Imbalance Underlies Hippocampal Atrophy in Individuals With 22q11.2 Deletion Syndrome With Psychotic Symptoms. In: Biological psychiatry, 2023. doi: 10.1016/j.biopsych.2023.03.021
Main files (2)
Article (Accepted version)
accessLevelRestrictedaccessLevelPublic 04/02/2024
Article (Published version) - in press
Secondary files (2)
ISSN of the journal0006-3223

Technical informations

Creation08/18/2023 12:35:00 PM
First validation08/23/2023 1:00:02 PM
Update time08/23/2023 1:00:02 PM
Status update08/23/2023 1:00:02 PM
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