Impaired cortical inhibition in patients with unipolar major depression: evidence from transcranial magnetic stimulation of the motor cortex

Aims: Measurement of central cortical inhibitory mechanisms, especially associated with gamma-aminobutyric acid (GABA) neurotransmission, is possible using transcranial magnetic stimulation (TMS) of the motor cortex. Several previous reports suggested that GABA-ergic neurotransmission may play a role in the pathophysiology of major depression.

Methods: By means of TMS, different parameters of cortical excitability, including motor threshold, the cortical silent period and intracortical inhibition/facilitation, were investigated in medication-free patients with unipolar depression and age- and gender-matched healthy volunteers.

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

Conclusions: Our data provide evidence for alterations of cortical inhibitory pathways suggesting reduced GABA-ergic tone in the motor cortex. It also demonstrates hemispheric asymmetry as measured with the motor threshold. Last, the data suggest that TMS measures may serve as a biological marker for major depression and moreover may be a valuable tool for investigating cortical changes in the course of both pharmacological and non-pharmacological treatment interventions.