title: Cortical inhibitory and excitatory function in drug-naive generalized anxiety disorder.
abstract: A growing body of evidence suggests that deficits in GABAergic inhibitory and glutamatergic excitatory neurotransmission may be involved in the core pathophysiology of generalized anxiety disorder (GAD), a disease characterized by pathological anxious worrying. The aim of the present study was to measure motor cortical excitability by paired-pulse transcranial magnetic stimulation (ppTMS) in patients with GAD.
  
  
  
  ppTMS measurements of excitation and inhibition from bilateral motor cortices were investigated in 26 right-handed GAD patients who were drug-naïve (half of them with a comorbidity of major depressive disorder) and 35 right-handed age- and sex-matched healthy controls. Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI) were studied; evidence indicated that these are mainly mediated by GABA-A receptors, glutamate receptors, and GABA-B receptors, respectively.
  
  
  
  After correcting for multiple comparisons, GAD patients had significantly lower left ICF (p < 0.001, Cohen's d = 1.348) and right ICF (p = 0.001, Cohen's d = 0.963), but not SICI and LICI, than did healthy controls. No significant difference of the ICF values was found between GAD with and without depressive disorders. Multivariate linear regression analysis revealed that left ICF (B = -4.990, 95% CI = -8.821 to -1.039, p = 0.007) and group (B = 13.179, 95% CI = 10.208 to 16.149, p = 0.001) predicted anxiety symptoms significantly.
  
  
  
  The present study provided direct evidence to support that generalized anxiety disorder is characterized by impaired intra-cortical facilitation of motor cortex, suggesting glutamate-related excitatory dysfunction may play a key role in pathological anxiety.
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Cognitive Neuroscience, National Central University, Jhongli, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. Electronic address: ctli2@vghtpe.gov.tw.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Li
authors.affiliation: Translational Imaging Research Center, College of Medicine, Taipei Medical University, Taiwan; Department of Radiology, School of Medicine, Taipei Medical University, Taiwan; Department of Physical Therapy and Assistive Technology, National Yang-Ming University, Taiwan.
authors.forename: Chia-Feng
authors.initials: CF
authors.lastname: Lu
authors.affiliation: Department and Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hui-Ching
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Department of Neurology, Chang-Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ying-Zu
authors.initials: YZ
authors.lastname: Huang
authors.affiliation: Institute of Cognitive Neuroscience, National Central University, Jhongli, Taiwan.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Juan
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tung-Ping
authors.initials: TP
authors.lastname: Su
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ya-Mei
authors.initials: YM
authors.lastname: Bai
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Mu-Hong
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Lin
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000503:physiopathology*; D019054:Evoked Potentials, Motor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009433:Neural Inhibition; D050781:Transcranial Magnetic Stimulation
keywords: GABA; Generalized anxiety disorder; Glutamate; Intracortical facilitation; Intracortical inhibition; Motor cortex