Abstract
Depressive disorders are one of the leading causes of disability worldwide. Transcranial direct current stimulation (tDCS) is a safe, simple, non-invasive brain stimulation technique showing considerable effectiveness in improving depressive symptoms. Most studies to date have applied anodal tDCS to the left dorsolateral prefrontal cortex (DLPFC), in line with the hypothesis that depressed patients exhibit relative hypoactivity in the left DLPFC compared to the right. Considering the emerging role of the cerebellum in emotional processes, we aimed to study the effect of combining bilateral cerebellar tDCS with the commonly used bifrontal stimulation in patients with severe depression. This open-label pilot study entailed the simultaneous administration of bilateral cerebellar (anode over the left cerebellum, cathode over the right cerebellum) and bilateral frontal (anode over the left DLPFC, cathode over the right DLPFC) tDCS to patients (N = 12) with treatment-resistant depression. The 21-item Hamilton Depression Rating Scale (HDRS) and Beck's Depression Inventory-II (BDI-II) were selected as outcome measures. Electric fields distribution originating from this novel electrode montage was obtained by a computational method applied to a realistic human head model. We observed a 30% reduction of both clinician-rated and self-reported severity of depressive symptoms after only five days (10 sessions) of treatment. Younger age was associated with greater clinical improvement. Adverse events were similar to those of the conventional electrodes montage. The modelling studies demonstrated that the electric fields generated by each pair of electrodes are primarily distributed in the cortical areas under the electrodes. In conclusion, the cerebellum could represent a promising adjunctive target for tDCS interventions in patients with TRD, particularly for younger patients.