Neurophysiological biomarkers of major depressive disorder by means of transcranial magnetic stimulation

Major depressive disorder (MDD) is characterized by both psychological and physiological changes with debilitating consequences, that lead to significant impairments in daily functioning and overall quality of life. With limited progress in treatment outcomes, there is a growing need to identify robust biomarkers that address the physiological underpinnings of MDD. Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is a means of directly evaluating the function of excitatory and inhibitory systems in the stimulated area, with high spatiotemporal resolution. However, large interindividual variability and presence of artifacts in measurements limit potential use of TMS – EEG for biomarker identification. In this thesis, the aim was to identify optimized stimulation targets in the left dorsolateral prefrontal cortex (L-DLPFC), to observe TMS evoked potentials (TEPs), and to investigate whether these TEP characteristics correlate with subjective depressive symptoms. Firstly, early TEPs in the L-DLPFC (<60ms) were successfully obtained by using TMS mapping, which represent genuine neuronal activity of the stimulated area. Secondly, the present study identified an altered excitation / inhibition balance in MDD. The ratio of the second peak-to-peak over the first peak-to-peak of the TEP waveform significantly correlated with MDD symptoms, as measured by the Patient Health Questionnaire (PHQ-9) and Quick Inventory of Depressive Symptomatology (QIDS). Consequently, this altered ratio has significant potential to be used as an objective biomarker, alongside existing subjective symptom scores.