title: Decreased thalamic glutamate level in unmedicated adult obsessive-compulsive disorder patients detected by proton magnetic resonance spectroscopy.
abstract: BACKGROUND
  Previous neuroimaging studies implied that the dysfunction of cortico-striato-thalamo-cortical (CSTC) circuit served as the neural basis for the pathophysiology of obsessive-compulsive disorder (OCD). The imbalances in neuronal metabolite and neurotransmitter within CSTC circuit have been shown as the leading reasons of the OCD onset. The aim of this study is to investigate the metabolic alterations, especially the glutamatergic signal dysfunction within CSTC circuit, and the relationships between neural metabolites and the symptom severity of OCD patients.
  
  
  METHODS
  Single voxel magnetic resonance spectroscopy (MRS) was conducted in medial prefrontal cortex (mPFC) and bilateral thalamus areas for thirteen unmedicated adult OCD patients with age-, gender-, and education-matched healthy controls. Quantification and multivariate analysis were performed to identify vital metabolic biomarkers for patients and healthy controls group differentiation. Moreover, we performed Spearman׳s rank correlation analysis for OCD patients to examine the relationship between the metabolite concentration level and OCD symptomatology.
  
  
  RESULTS
  Patients with OCD showed significantly decreased glutamate level in mPFC (p=0.021) and right thalamus (p=0.039), and significantly increased choline compounds in left thalamus (p=0.044).The glutamate in right thalamus was shown as the most important metabolite for group separation from multivariate analysis (Q(2)=0.134) and was significantly correlated with the patients׳ compulsion scores (Spearman r=-0.674, p=0.016).
  
  
  CONCLUSIONS
  Limited sample size, the use of creatine and phosphocreatine (Cr) ratios rather than absolute concentrations and unresolved glutamine (Gln) are limitations of the present study.
  
  
  CONCLUSIONS
  Our study results consolidated the hypothesis about glutamatergic signaling dysfunction in OCD. To our knowledge, it is the first finding about a reduced thalamic glutamate level in adult unmedicated OCD patients. The dysregulation of glutamate serves as a potential target for the OCD pharmacotherapy and the detailed mechanisms underlying the glutamate alterations within CSTC circuits merit further investigations.
authors.affiliation: Med-X Research Institute, Shanghai Jiaotong University, Shanghai 200030, China; School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai 200240, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: fanqing_98@sina.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Departments of Pediatrics, Neuroscience, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute at Texas Children׳s Hospital, Houston, TX 77030, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Haiyin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Zongfeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tan
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Zeping
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Med-X Research Institute, Shanghai Jiaotong University, Shanghai 200030, China; School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai 200240, China.
authors.forename: Shanbao
authors.initials: S
authors.lastname: Tong
authors.affiliation: Departments of Pediatrics, Neuroscience, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute at Texas Children׳s Hospital, Houston, TX 77030, USA.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Maletic-Savatic
authors.affiliation: Med-X Research Institute, Shanghai Jiaotong University, Shanghai 200030, China; School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai 200240, China. Electronic address: yaoli118@gmail.com.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D003401:Creatine / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D066244:Proton Magnetic Resonance Spectroscopy; D018401:Sample Size; D012720:Severity of Illness Index; D015398:Signal Transduction; D013788:Thalamus / Q000378:metabolism*
chemical_list: D010725:Phosphocreatine; D018698:Glutamic Acid; D003401:Creatine
keywords: Glutamate; Magnetic resonance spectroscopy; Medial prefrontal cortex; Multivariate analysis; Obsessive–compulsive disorder; Thalamus