title: Abnormal Anterior Cingulate N-Acetylaspartate and Executive Functioning in Treatment-Resistant Depression After rTMS Therapy.
abstract: BACKGROUND
  Cognitive impairment is a key feature of treatment-resistant depression (TRD) and can be related to the anterior cingulate cortex (ACC) function. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. However, no studies to date have investigated the association between neurobiochemical changes within the anterior cingulate and executive dysfunction measured in TRD being treated with rTMS.
  
  
  METHODS
  Thirty-two young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study [active (n=18) vs. sham (n=14)]. ACC metabolism was investigated before and after high-frequency (15 Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy (1H-MRS). The results were compared with 28 age- and gender-matched healthy controls. Executive functioning was measured with the Wisconsin Card Sorting Test (WCST) among 34 subjects with TRD and 28 healthy subjects.
  
  
  RESULTS
  Significant reductions in N-acetylaspartate (NAA) and choline-containing Compound levels in the left ACC were found in subjects with TRD pre-rTMS when compared with healthy controls. After successful treatment, NAA levels increased significantly in the left ACC of subjects and were not different from those of age-matched controls. In the WCST, more perseverative errors and fewer correct numbers were observed in TRD subjects at baseline. Improvements in both perseverative errors and correct numbers occurred after active rTMS. In addition, improvement of perseverative errors was positively correlated with enhancement of NAA levels in the left ACC in the active rTMS group.
  
  
  CONCLUSIONS
  Our results suggest that the NAA concentration in the left ACC is associated with an improvement in cognitive functioning among subjects with TRD response to active rTMS.
authors.affiliation: Guangdong Mental Health Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Affiliated School of Medicine of South China University of Technology, Guangzhou, Guangdong, P.R. China (Drs Zheng, Jia, Wu, Zhang, and Fan, and Mr Guo, Quan, Li, and Ms He); Department of Radiology, Guangzhou Hui-Ai Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China (Dr Wu); Pharmacy Department of Guangdong General Hospital, Guangdong academy of medical sciences, Guangzhou, Guangdong, P.R. China (Ms Huang). hgm198103@163.com.
authors.forename: Huirong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Guangdong Mental Health Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Affiliated School of Medicine of South China University of Technology, Guangzhou, Guangdong, P.R. China (Drs Zheng, Jia, Wu, Zhang, and Fan, and Mr Guo, Quan, Li, and Ms He); Department of Radiology, Guangzhou Hui-Ai Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China (Dr Wu); Pharmacy Department of Guangdong General Hospital, Guangdong academy of medical sciences, Guangzhou, Guangdong, P.R. China (Ms Huang).
authors.forename: Fujun
authors.initials: F
authors.lastname: Jia
authors.affiliation: Guangdong Mental Health Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Affiliated School of Medicine of South China University of Technology, Guangzhou, Guangdong, P.R. China (Drs Zheng, Jia, Wu, Zhang, and Fan, and Mr Guo, Quan, Li, and Ms He); Department of Radiology, Guangzhou Hui-Ai Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China (Dr Wu); Pharmacy Department of Guangdong General Hospital, Guangdong academy of medical sciences, Guangzhou, Guangdong, P.R. China (Ms Huang).
authors.forename: Guangquan
authors.initials: G
authors.lastname: Guo
authors.affiliation: Guangdong Mental Health Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Affiliated School of Medicine of South China University of Technology, Guangzhou, Guangdong, P.R. China (Drs Zheng, Jia, Wu, Zhang, and Fan, and Mr Guo, Quan, Li, and Ms He); Department of Radiology, Guangzhou Hui-Ai Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China (Dr Wu); Pharmacy Department of Guangdong General Hospital, Guangdong academy of medical sciences, Guangzhou, Guangdong, P.R. China (Ms Huang).
authors.forename: Dongming
authors.initials: D
authors.lastname: Quan
authors.affiliation: Guangdong Mental Health Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Affiliated School of Medicine of South China University of Technology, Guangzhou, Guangdong, P.R. China (Drs Zheng, Jia, Wu, Zhang, and Fan, and Mr Guo, Quan, Li, and Ms He); Department of Radiology, Guangzhou Hui-Ai Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China (Dr Wu); Pharmacy Department of Guangdong General Hospital, Guangdong academy of medical sciences, Guangzhou, Guangdong, P.R. China (Ms Huang).
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Guangdong Mental Health Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Affiliated School of Medicine of South China University of Technology, Guangzhou, Guangdong, P.R. China (Drs Zheng, Jia, Wu, Zhang, and Fan, and Mr Guo, Quan, Li, and Ms He); Department of Radiology, Guangzhou Hui-Ai Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China (Dr Wu); Pharmacy Department of Guangdong General Hospital, Guangdong academy of medical sciences, Guangzhou, Guangdong, P.R. China (Ms Huang).
authors.forename: Huawang
authors.initials: H
authors.lastname: Wu
authors.affiliation: Guangdong Mental Health Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Affiliated School of Medicine of South China University of Technology, Guangzhou, Guangdong, P.R. China (Drs Zheng, Jia, Wu, Zhang, and Fan, and Mr Guo, Quan, Li, and Ms He); Department of Radiology, Guangzhou Hui-Ai Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China (Dr Wu); Pharmacy Department of Guangdong General Hospital, Guangdong academy of medical sciences, Guangzhou, Guangdong, P.R. China (Ms Huang).
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Guangdong Mental Health Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Affiliated School of Medicine of South China University of Technology, Guangzhou, Guangdong, P.R. China (Drs Zheng, Jia, Wu, Zhang, and Fan, and Mr Guo, Quan, Li, and Ms He); Department of Radiology, Guangzhou Hui-Ai Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China (Dr Wu); Pharmacy Department of Guangdong General Hospital, Guangdong academy of medical sciences, Guangzhou, Guangdong, P.R. China (Ms Huang).
authors.forename: Changhe
authors.initials: C
authors.lastname: Fan
authors.affiliation: Guangdong Mental Health Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Affiliated School of Medicine of South China University of Technology, Guangzhou, Guangdong, P.R. China (Drs Zheng, Jia, Wu, Zhang, and Fan, and Mr Guo, Quan, Li, and Ms He); Department of Radiology, Guangzhou Hui-Ai Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China (Dr Wu); Pharmacy Department of Guangdong General Hospital, Guangdong academy of medical sciences, Guangzhou, Guangdong, P.R. China (Ms Huang).
authors.forename: Xiajun
authors.initials: X
authors.lastname: He
authors.affiliation: Guangdong Mental Health Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Affiliated School of Medicine of South China University of Technology, Guangzhou, Guangdong, P.R. China (Drs Zheng, Jia, Wu, Zhang, and Fan, and Mr Guo, Quan, Li, and Ms He); Department of Radiology, Guangzhou Hui-Ai Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China (Dr Wu); Pharmacy Department of Guangdong General Hospital, Guangdong academy of medical sciences, Guangzhou, Guangdong, P.R. China (Ms Huang).
authors.forename: Huiyan
authors.initials: H
authors.lastname: Huang
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D061218:Depressive Disorder, Treatment-Resistant / Q000503:physiopathology* / Q000523:psychology / Q000628:therapy*; D004311:Double-Blind Method; D056344:Executive Function / Q000502:physiology; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D066244:Proton Magnetic Resonance Spectroscopy; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate
keywords: 1H-MRS; N-acetylaspartate; anterior cingulate; depression; executive functioning; rTMS