Cortical inhibitory and excitatory function in drug-naive generalized anxiety disorder

CT Li, CF Lu, HC Lin, YZ Huang, CH Juan, TP Su… - Brain stimulation, 2017 - Elsevier
CT Li, CF Lu, HC Lin, YZ Huang, CH Juan, TP Su, YM Bai, MH Chen, WC Lin
Brain stimulation, 2017Elsevier
Background 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. Methods ppTMS
measurements of excitation and inhibition from bilateral motor cortices were investigated in …
Background
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.
Methods
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.
Results
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.
Conclusion
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.
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