• Paul E Croarkin, Paul A Nakonezny, Mustafa M Husain, Tabatha Melton, Jeylan S Buyukdura, Betsy D Kennard, Graham J Emslie, F Andrew Kozel, and Zafiris J Daskalakis.
• Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota 55905, USA. croarkin.paul@mayo.edu
• JAMA Psychiatry. 2013 Mar 1;70(3):291-9.

ContextConverging lines of evidence implicate the glutamate and γ-aminobutyric acid neurotransmitter systems in the pathophysiology of major depressive disorder. Transcranial magnetic stimulation cortical excitability and inhibition paradigms have been used to assess cortical glutamatergic and γ-aminobutyric acid-mediated tone in adults with major depressive disorder, but not in children and adolescents.ObjectiveTo compare measures of cortical excitability and inhibition with 4 different paradigms in a group of children and adolescents with major depressive disorder vs healthy controls.DesignCross-sectional study examining medication-free children and adolescents (aged 9-17 years) with major depressive disorder compared with healthy controls. Cortical excitability was assessed with motor threshold and intracortical facilitation measures. Cortical inhibition was measured with cortical silent period and intracortical inhibition paradigms.SettingUniversity-based child and adolescent psychiatry clinic and neurostimulation laboratory.PatientsTwenty-four participants with major depressive disorder and 22 healthy controls matched for age and sex. Patients with major depressive disorder were medication naive and had moderate to severe symptoms based on an evaluation with a child and adolescent psychiatrist and scores on the Children's Depression Rating Scale-Revised.Main Outcome MeasuresMotor threshold, intracortical facilitation, cortical silent period, and intracortical inhibition.ResultsCompared with healthy controls, depressed patients had significantly increased intracortical facilitation at interstimulus intervals of 10 and 15 milliseconds bilaterally. There were no significant group differences in cortical inhibition measures.ConclusionsThese findings suggest that major depressive disorder in children and adolescents is associated with increased intracortical facilitation and excessive glutamatergic activity.

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