The present study involves the administration of three types of interventions in patients with depressive episode in the context of DDM. Two-thirds of the patients will carry out a course of excitatory tDCS sessions on the left DLPFC, so as to improve attention regulation on information characterized by negative emotions and have an antidepressant effect, simultaneously with the performance of a task, the attentional training technique (ATT), aimed at achieve effective management of emotions characterized by negative emotions and which constitutes a fundamental exercise of MCT. In half of the patients who will undergo tDCS treatment, after each session of stimulation, an MCT session will be carried out. In addition, before and after the cycle of tDCS sessions and MCT sessions will be explored, in a subgroup of patients, in the context of a pilot study, the TMS- EEG of the change in depressive symptomatology, which can be correlated with the different proposed therapeutic interventions.

The study - interventional, nonpharmacological, using medical devices, nonprofit - is aimed at evaluating the potential effectiveness of a multimodal intervention for the treatment of unipolar depression. The intervention involves the use of a neuro-stimulation technique, the Transcranial Direct Current Stimulation (transcranial Direct Current Stimulation - tDCS), combined with a psychotherapy intervention, metacognitive therapy (MetaCognitive Therapy, MCT). TDCS is a noninvasive neurostimulation technique involving the transcranial application of a low-amperage electric current at a region of the cerebral cortex involved in the pathogenesis of major depression, the dorsolateral prefrontal cortex. It has been demonstrated how such stimulation has a neuromodulating effect on synaptic plasticity, with efficacy in unipolar major depression. The technique also has a good safety, as it is not associated with major side effects. MCT is based on the metacognitive model, according to which psychopathological processes are consequent to a cognitive style characterized by repetitive forms of thinking (such as rumination) and maladaptive behaviors such as avoidance and thought suppression. The MCT, through attention training techniques, detached mindfulness and behavioral interventions on metacognitions, has shown effectiveness in major depressive disorder comparable to that of psychotherapeutic interventions considered, within psychotherapies, to be first-line such as cognitive-behavioral therapy. The experimental design will be that of a randomized, double-blind study with three arms of treatment, each consisting of 8 sessions, involving the administration of 1) the neurostimulation intervention (tDCS), 2) of the psychotherapeutic intervention alone (MCT), 3) of both techniques in consecution (tDCS-MCT). This design is aimed at evaluating a potential additive/synergistic effect of the two interventions when combined. During the tDCS sessions, each lasting 20 minutes, the patient will apply the technique of attention training, aimed at further activating the region stimulated by neurostimulation, so as to so as to amplify the plasticity stimulated by tDCS, achieving a synergistic effect. To follow, a 40-minute MCT session will be carried out. The effectiveness of these interventions will be assessed by heteroadministered and self-administered at time zero, after treatment, at two follow-ups of 6 and 12 months. Before and after the treatment cycle (tDCS sessions and MCT sessions), a subgroup of patients will be explored, in the context of a pilot study, the TMS-EEG correlates of the change in symptomatology depression, which can be correlated with the different proposed therapeutic interventions.

Inclusion Criteria:

• Ability to provide informed consent to study
• Ability to understand and speak the Italian language
• DSM-5 diagnosis of Major Depressive Disorder.
• Ongoing depressive episode of at least moderate intensity (HAM-D> 18)

Exclusion Criteria:

• Previous tDCS sessions with significant side effects
• Positive personal history for seizures
• Positive family history for epileptic disease
• Positive personal history for neurological disease
• Positive personal history for head trauma with loss of consciousness
• Positive personal history for frequent and severe headaches
• Positive personal history for neurosurgical procedures
• Prior implantation of neurostimulation implants (DBS, VNS, etc.)
• Prior implantation of defibrillator or pace-maker
• Possibility of pregnancy or established pregnancy
• Substance or alcohol abuse in the past 6 months
• Positive personal history for schizophrenia or schizoaffective disorder
• Positive personal history of intellectual disability ("mental retardation")
• Current hospitalization
• Cardiac, respiratory, renal, hepatic failure, immunosuppression status