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

Cheng Ta Li, Chia Feng Lu, Hui Ching Lin, Ying Zu Huang, Chi Hung Juan, Tung Ping Su, Ya Mei Bai, Mu Hong Chen, Wei Chen Lin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)604-608
Number of pages5
JournalBrain Stimulation
Volume10
Issue number3
DOIs
Publication statusPublished - May 1 2017

Fingerprint

Anxiety Disorders
Pharmaceutical Preparations
Transcranial Magnetic Stimulation
Motor Cortex
Anxiety
GABA-B Receptors
Major Depressive Disorder
GABA-A Receptors
Depressive Disorder
Synaptic Transmission
Comorbidity
Glutamic Acid
Linear Models
Regression Analysis
Inhibition (Psychology)

Keywords

  • GABA
  • Generalized anxiety disorder
  • Glutamate
  • Intracortical facilitation
  • Intracortical inhibition
  • Motor cortex

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biophysics
  • Clinical Neurology

Cite this

Li, C. T., Lu, C. F., Lin, H. C., Huang, Y. Z., Juan, C. H., Su, T. P., ... Lin, W. C. (2017). Cortical inhibitory and excitatory function in drug-naive generalized anxiety disorder. Brain Stimulation, 10(3), 604-608. https://doi.org/10.1016/j.brs.2016.12.007

Cortical inhibitory and excitatory function in drug-naive generalized anxiety disorder. / Li, Cheng Ta; Lu, Chia Feng; Lin, Hui Ching; Huang, Ying Zu; Juan, Chi Hung; Su, Tung Ping; Bai, Ya Mei; Chen, Mu Hong; Lin, Wei Chen.

In: Brain Stimulation, Vol. 10, No. 3, 01.05.2017, p. 604-608.

Research output: Contribution to journalArticle

Li, CT, Lu, CF, Lin, HC, Huang, YZ, Juan, CH, Su, TP, Bai, YM, Chen, MH & Lin, WC 2017, 'Cortical inhibitory and excitatory function in drug-naive generalized anxiety disorder', Brain Stimulation, vol. 10, no. 3, pp. 604-608. https://doi.org/10.1016/j.brs.2016.12.007
Li, Cheng Ta ; Lu, Chia Feng ; Lin, Hui Ching ; Huang, Ying Zu ; Juan, Chi Hung ; Su, Tung Ping ; Bai, Ya Mei ; Chen, Mu Hong ; Lin, Wei Chen. / Cortical inhibitory and excitatory function in drug-naive generalized anxiety disorder. In: Brain Stimulation. 2017 ; Vol. 10, No. 3. pp. 604-608.
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abstract = "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-na{\"i}ve (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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AU - Juan, Chi Hung

AU - Su, Tung Ping

AU - Bai, Ya Mei

AU - Chen, Mu Hong

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AB - 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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