title: Decreased mRNA expression for the two subunits of system xc(-), SLC3A2 and SLC7A11, in WBC in patients with schizophrenia: Evidence in support of the hypo-glutamatergic hypothesis of schizophrenia.
abstract: BACKGROUND
  The cystine/glutamate antiporter system xc(-), playing a critical role in the regulation of glutamate release, might be implicated in the pathogenesis of schizophrenia. This study examined whether peripheral expressions of the system xc(-) subunits are characteristic of schizophrenia.
  
  
  METHODS
  Expression of system xc(-) genes including SLC3A2 and SLC7A11 in peripheral WBCs of patients with schizophrenia and healthy individuals were measured using quantitative PCR. Both psychotropic-free and medicated patients with schizophrenia were recruited.
  
  
  RESULTS
  A total of 96 schizophrenia patients (48 medicated and 48 drug-free) and 96 healthy individuals were enrolled. The mRNA expression levels using the 2(-ΔΔC)T Method of both SLC3A2 and SLC7A11 in WBCs of schizophrenia patients were markedly lower than that of healthy individuals (0.22 and 0.48, respectively, the mRNA expression level of normal controls was normalized to 1). There was no significant difference between medicated and drug-free patients in the mRNA expressions of both SLC3A2 and SLC7A11. The Receiver Operating Characteristics (ROC) analysis of SLC3A2 mRNA levels using ΔΔCT values for drug-free schizophrenia patients vs. healthy controls determined an optimal cutoff value, 0.801, with high sensitivity (1.000) and modest specificity (0.694) (area under curve of ROC = 0.794).
  
  
  CONCLUSIONS
  This is the first study indicating that the peripheral mRNA expression levels of SLC7A11 and SLC3A2 may be lower in patients with schizophrenia than healthy individuals. The finding supports the hypo-glutamatergic neurotransmission hypothesis in schizophrenia. Whether mRNA expression of system xc(-) subunits genes, particularly SLC3A2, could serve as a potential biomarker of schizophrenia needs further studies.
authors.affiliation: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Chieh-Hsin
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Lin
authors.affiliation: Department of General Psychiatry, Tsaotun Psychiatric Center, Taichung, Taiwan.
authors.forename: Chun-Yuan
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Kai-Suan Psychiatric Hospital, Kaohsiung, Taiwan.
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chiung-Hsien
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yu-Jhen
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan. Electronic address: hylane@gmail.com.
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
mesh_terms: D000293:Adolescent; D000328:Adult; D027182:Amino Acid Transport System y+ / Q000378:metabolism*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D019540:Area Under Curve; D005260:Female; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012372:ROC Curve; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D027182:Amino Acid Transport System y+; D014150:Antipsychotic Agents; D027282:Fusion Regulatory Protein 1, Heavy Chain; D012333:RNA, Messenger; C545989:SLC3A2 protein, human; C118895:SLC7A11 protein, human; D018698:Glutamic Acid
keywords: SLC3A2; SLC7A11; Schizophrenia; System x(c)(−); glutamate