title: Comparison of the density of gamma-aminobutyric acid in the ventromedial prefrontal cortex of patients with first-episode psychosis and healthy controls.
abstract: BACKGROUND
  Abnormality in the concentration and functioning of gamma-aminobutyric acid (γ-aminobutyric acid, GABA) in the brain is not only an important hypothetical link to the cause of schizophrenia but it may also be correlated with the cognitive decline and negative symptoms of schizophrenia. Studies utilizing high field magnetic resonance spectroscopy (MRS) report abnormal density of GABA in the ventromedial prefrontal cortex (vmPFC) of patients with chronic schizophrenia, but these results may be confounded by study participants' prior use of antipsychotic medications.
  
  
  OBJECTIVE
  Compare the density of GABA in the vmPFC of patients with first-episode psychosis to that in healthy controls and assess the relationship of GABA density in the vmPFC to the severity of psychotic symptoms.
  
  
  METHODS
  Single-voxel (1)H-MRS was used to assess the concentration of GABA and other metabolites in the vmPFC of 22 patients with first-episode psychosis (10 with schizophrenia and 12 with schizophreniform disorder) and 23 healthy controls. Thirteen of the 22 patients were drug-naïve and 9 had used antipsychotic medication for less than 3 days. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the severity of psychotic symptoms in the patient group.
  
  
  RESULTS
  The mean (sd) GABA density in the vmPFC was significantly higher in patients than in controls (2.28 [0.54] v. 1.93 [0.32] mM, t=2.62, p=0.012). The densities of other metabolites - including N-acetylaspartic acid (NAA), glutamic acid (GLU), and glutamine (GLN) - were not significantly different between patients and controls. Among the patients, GABA density in the vmPFC was not significantly correlated with PANSS total score or with any of the three PANSS subscale scores for positive symptoms, negative symptoms, and general psychopathology. GABA concentration was not associated with the duration of illness, but it was significantly correlated with patient age (r=0.47, p=0.026).
  
  
  CONCLUSIONS
  Elevation of GABA density in the vmPFC of patients with first-episode psychosis confirms that this abnormality is independent of medication use. The failure to find a correlation of GABA density in the vmPFC with the severity of psychotic symptoms needs to be confirmed in larger studies, but it suggests that there are several intervening steps between brain pathology and clinical symptoms.
authors.affiliation: First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Shanghai Jiading District Mental Health Center, Shanghai, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Song
authors.affiliation: First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Mei
authors.affiliation: First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jianye
authors.initials: J
authors.lastname: Zhang
authors.affiliation: First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Hongkou District Mental Health Center, Shanghai, China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Chen
authors.affiliation: First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yingchan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Kaida
authors.initials: K
authors.lastname: Jiang
authors.affiliation: First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Dengtang
authors.initials: D
authors.lastname: Liu
keywords: China; drug-naïve; first-episode psychosis; first-episode schizophrenia; gamma-aminobutyric acid; magnetic resonance spectroscopy; ventromedial prefrontal cortex