title: Prefrontal GABA Levels Measured With Magnetic Resonance Spectroscopy in Patients With Psychosis and Unaffected Siblings.
abstract: The authors sought to compare GABA levels in treated and untreated patients with psychosis with levels in their unaffected siblings and healthy control subjects, and to assess the effects of antipsychotic medications on GABA levels.
  
  
  
  GABA+ levels (i.e., including signal from unrelated proteins or macromolecules) referenced to creatine or water were studied with J-edited proton spectroscopy in the dorsal anterior cingulate cortex of 289 individuals: 184 healthy control subjects, 83 treated patients with psychosis, 25 untreated patients, 31 unaffected siblings, and 17 patients studied both while off all medications and while on a single antipsychotic.
  
  
  
  GABA+ levels in the dorsal anterior cingulate did not differ between untreated patients and healthy controls. For treated patients, levels were modestly lower for GABA+/creatine but did not differ for GABA+/water compared with healthy controls. For both GABA+ measures, unaffected siblings had significantly lower levels compared with controls. GABA+/creatine showed a modest degree of familiality (intraclass correlation=0.36). Antipsychotic dosage was negatively correlated with GABA+ levels, but the on-off medication studies indicated no difference in GABA+ levels on antipsychotics compared with off antipsychotics.
  
  
  
  GABA+/creatine in the dorsal anterior cingulate may constitute an intermediate phenotype with low effect size for psychosis, but GABA+/water measures do not fully support this conclusion. Low GABA+ levels in unaffected siblings could suggest a genetic association, but the failure to find consistent evidence of this phenotype in the patients themselves weakens genetic inference on risk for psychosis. Replication in independent samples of siblings is warranted to confirm the potential genetic risk association.
authors.affiliation: From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Stefano
authors.initials: S
authors.lastname: Marenco
authors.affiliation: From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
authors.affiliation: From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Susan
authors.initials: S
authors.lastname: Kuo
authors.affiliation: From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: van der Veen
authors.affiliation: From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.affiliation: From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Katherine
authors.initials: K
authors.lastname: DeJong
authors.affiliation: From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Barnett
authors.affiliation: From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Apud
authors.affiliation: From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Dwight
authors.initials: D
authors.lastname: Dickinson
authors.affiliation: From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.affiliation: From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Karen F
authors.initials: KF
authors.lastname: Berman
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism*; D035781:Siblings; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D005680:gamma-Aminobutyric Acid