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Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.
Merritt, Kate; McCutcheon, Robert A; Aleman, André; Ashley, Sarah; Beck, Katherine; Block, Wolfgang; Bloemen, Oswald J N; Borgan, Faith; Boules, Christiana; Bustillo, Juan R; Capizzano, Aristides A; Coughlin, Jennifer M; David, Anthony; de la Fuente-Sandoval, Camilo; Demjaha, Arsime; Dempster, Kara; Do, Kim Q; Du, Fei; Falkai, Peter; Galinska-Skok, Beata; Gallinat, Jürgen; Gasparovic, Charles; Ginestet, Cedric E; Goto, Naoki; Graff-Guerrero, Ariel; Ho, Beng-Choon; Howes, Oliver; Jauhar, Sameer; Jeon, Peter; Kato, Tadafumi; Kaufmann, Charles A; Kegeles, Lawrence S; Keshavan, Matcheri S; Kim, Sang-Young; King, Bridget; Kunugi, Hiroshi; Lauriello, J; León-Ortiz, Pablo; Liemburg, Edith; Mcilwain, Meghan E; Modinos, Gemma; Mouchlianitis, Elias; Nakamura, Jun; Nenadic, Igor; Öngür, Dost; Ota, Miho; Palaniyappan, Lena; Pantelis, Christos; Patel, Tulsi; Plitman, Eric.
Afiliação
  • Merritt K; Division of Psychiatry, UCL, Institute of Mental Health, London, UK. K.merritt@ucl.ac.uk.
  • McCutcheon RA; Dept of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
  • Aleman A; Center for Brain Disorder and Cognitive Science, Shenzhen University, Shenzhen, China.
  • Ashley S; University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • Beck K; Division of Psychiatry, UCL, Institute of Mental Health, London, UK.
  • Block W; Psychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Bloemen OJN; Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Bonn, Germany.
  • Borgan F; Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands.
  • Boules C; Psychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Bustillo JR; Psychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Capizzano AA; Department of Psychiatry and Behavioral Sciences, Center for Psychiatric Research, University of New Mexico School of Medicine, Albuquerque, NM, USA.
  • Coughlin JM; Department of Radiology, Division of Neuroradiology, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI, 48109, USA.
  • David A; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • de la Fuente-Sandoval C; Division of Psychiatry, UCL, Institute of Mental Health, London, UK.
  • Demjaha A; Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
  • Dempster K; Neuropsychiatry Department, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
  • Do KQ; Psychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Du F; Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
  • Falkai P; Center for Psychiatric Neuroscience (CNP), Department of Psychiatry, Lausanne University Hospital-CHUV, Prilly-Lausanne, Switzerland.
  • Galinska-Skok B; Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
  • Gallinat J; Department of Psychiatry, University Hospital, LMU Munich, Nussbaumstrasse 7, 80336, Munich, Germany.
  • Gasparovic C; Department of Psychiatry, Medical University of Bialystok, Bialystok, Poland.
  • Ginestet CE; Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
  • Goto N; Mind Research Network, Albuquerque, NM, USA.
  • Graff-Guerrero A; Department of Biostatistics and Health Informatics (S2.06), Institute of Psychiatry, Psychology and Neuroscience King's College London, London, UK.
  • Ho BC; Department of Psychiatry, Kokura Gamo Hospital, Kitakyushu, Fukuoka, 8020978, Japan.
  • Howes O; Multimodal Neuroimaging Schizophrenia Group, Research Imaging Centre, Geriatric Mental Health Program at Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
  • Jauhar S; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
  • Jeon P; Psychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Kato T; Psychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Kaufmann CA; Department of Medical Biophysics, University of Western Ontario, London, ON, Canada.
  • Kegeles LS; Department of Psychiatry and Behavioral Science, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • Keshavan MS; Department of Psychiatry, Columbia University, New York State Psychiatric Institute (NYSPI), New York, NY, USA.
  • Kim SY; Columbia University, Department of Psychiatry, New York State Psychiatric Institute (NYSPI), New York, NY, USA.
  • King B; Harvard Medical School, 75 Fenwood Rd., Boston, MA, 02115, USA.
  • Kunugi H; Philips Healthcare, Seoul, 0463, Republic of Korea.
  • Lauriello J; Psychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • León-Ortiz P; National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-0031, Japan.
  • Liemburg E; Jefferson Health-Sidney Kimmel Medical College, Philadelphia, PA, USA.
  • Mcilwain ME; Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
  • Modinos G; Neuropsychiatry Department, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
  • Mouchlianitis E; Rob Giel Research Center, Department of Psychiatry, University Medical Center Groningen, Groningen, the Netherlands.
  • Nakamura J; School of Pharmacy, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
  • Nenadic I; Psychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Öngür D; Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, SE5 8AF, UK.
  • Ota M; Psychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Palaniyappan L; Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
  • Pantelis C; Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
  • Patel T; Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
  • Plitman E; National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-0031, Japan.
Mol Psychiatry ; 28(5): 2039-2048, 2023 05.
Article em En | MEDLINE | ID: mdl-36806762
ABSTRACT
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 < 0.001; glutamine CVR = 0.15, p = 0.003; Glx CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine CVR = 0.14, p = 0.05; Glx CVR = 0.25, p < 0.001) and thalamus (glutamate CVR = 0.16, p = 0.008; Glx CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age z = -0.03, p = 0.003, symptoms z = 0.007, p = 0.02) and temporal lobe (glutamate with age z = -0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age z = 0.01, p = 0.02, glutamine with symptoms z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = -0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate (z = -0.02, p < 0.001) and frontal white matter Glx (z = -0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esquizofrenia / Ácido Glutâmico Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Humans / Male Idioma: En Revista: Mol Psychiatry Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esquizofrenia / Ácido Glutâmico Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Humans / Male Idioma: En Revista: Mol Psychiatry Ano de publicação: 2023 Tipo de documento: Article