Evidence for impaired cortical inhibition in patients with unipolar major depression

Biol Psychiatry. 2006 Mar 1;59(5):395-400. doi: 10.1016/j.biopsych.2005.07.036. Epub 2005 Sep 28.


Background: Several lines of evidence suggest that central cortical inhibitory mechanisms, especially associated with gamma-aminobutyric acid (GABA) neurotransmission, may play a role in the pathophysiology of major depression. Transcranial magnetic stimulation is a useful tool for investigating central cortical inhibitory mechanisms associated with GABAergic neurotransmission in psychiatric and neurological disorders.

Methods: By means of transcranial magnetic stimulation, different parameters of cortical excitability, including motor threshold, the cortical silent period, and intracortical inhibition/facilitation, were investigated in 20 medication-free depressed patients and 20 age- and gender-matched healthy volunteers.

Results: Silent period and intracortical inhibition were reduced in depressed patients, consistent with a reduced GABAergic tone. Moreover, patients showed a significant hemispheric asymmetry in motor threshold.

Conclusions: This study provides evidence of reduced GABAergic tone and motor threshold asymmetry in patients with major depression.

MeSH terms

  • Adult
  • Brain Mapping
  • Cerebral Cortex / physiopathology*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / physiopathology*
  • Dominance, Cerebral / physiology
  • Electromyography
  • Female
  • Hand / innervation
  • Humans
  • Male
  • Middle Aged
  • Motor Cortex / physiopathology
  • Neural Inhibition / physiology*
  • Reference Values
  • Sensory Thresholds / physiology
  • Synaptic Transmission / physiology
  • Transcranial Magnetic Stimulation
  • gamma-Aminobutyric Acid / physiology


  • gamma-Aminobutyric Acid