Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.
Merritt K., McCutcheon RA., Aleman A., Ashley S., Beck K., Block W., Bloemen OJN., Borgan F., Boules C., Bustillo JR., Capizzano AA., Coughlin JM., David A., de la Fuente-Sandoval C., Demjaha A., Dempster K., Do KQ., Du F., Falkai P., Galińska-Skok B., Gallinat J., Gasparovic C., Ginestet CE., Goto N., Graff-Guerrero A., Ho B-C., Howes O., Jauhar S., Jeon P., Kato T., Kaufmann CA., Kegeles LS., Keshavan MS., Kim S-Y., King B., Kunugi H., Lauriello J., León-Ortiz P., Liemburg E., Mcilwain ME., Modinos G., Mouchlianitis E., Nakamura J., Nenadic I., Öngür D., Ota M., Palaniyappan L., Pantelis C., Patel T., Plitman E., Posporelis S., Purdon SE., Reichenbach JR., Renshaw PF., Reyes-Madrigal F., Russell BR., Sawa A., Schaefer M., Shungu DC., Smesny S., Stanley JA., Stone J., Szulc A., Taylor R., Thakkar KN., Théberge J., Tibbo PG., van Amelsvoort T., Walecki J., Williamson PC., Wood SJ., Xin L., Yamasue H., McGuire P., Egerton A., 1H-MRS in Schizophrenia Investigators None.
Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p