Elsevier

Biological Psychiatry

Volume 59, Issue 5, 1 March 2006, Pages 395-400
Biological Psychiatry

Original article
Evidence for Impaired Cortical Inhibition in Patients with Unipolar Major Depression

https://doi.org/10.1016/j.biopsych.2005.07.036Get rights and content

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.

Section snippets

Patients and Healthy Control Subjects

The study was approved by the Ethics committee of the Benjamin Franklin University Hospital of the Free University of Berlin. Inpatients and outpatients with a major depressive episode meeting the DSM-IV criteria were recruited from the Department of Psychiatry, Free University of Berlin. Out of a larger sample of 84 patients, 20 were free of antidepressants, anticonvulsants, mood stabilizers, or benzodiazepine treatment for at least 4 weeks due to intolerance or nonresponse. These patients

Subjects

Subject demographics are given in Table 1. Patients and volunteers did not differ in demographic variables.

Amplitudes of Motor Evoked Potentials

Mean amplitudes of 10 motor evoked potentials were 1.2 ± .4 mV at baseline and 1.3 ± .3 mV after termination of the measurements of motor cortical excitability.

Motor Threshold

Motor threshold of the right hemisphere was lower in depressed patients compared with normal volunteers, but left hemisphere MT did not differ between the groups (see Table 2,Figure 1). There was an interaction between group and

Discussion

Our results demonstrate that medication-free patients with major depression have significant changes in motor cortical inhibition compared with healthy volunteers, as measured with TMS. Our findings of reduced cortical silent period and intracortical inhibition are consistent with the hypothesis of a contribution of central inhibitory circuits in the pathophysiology of depressive symptoms supported by previous animal, neurochemical, and neuroimaging studies. The question remains, however,

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