Clinical trials

Background: 30-50% of patients with Major Depressive Disorder (MDD) do not respond adequately despite two or more antidepressant treatments with proper dosage and timing of administration, configuring a condition of Treatment-Resistant Depression (TRD). Repetitive Transcranial Magnetic Stimulation (rTMS) is a neuromodulation technique that uses a magnetic field to stimulate focal cortical brain regions and it has been approved by the FDA for the treatment of TRD. Accelerated rTMS (arTMS) protocols involve multiple daily sessions of rTMS and they have been shown to be equally effective and safe compared to rTMS protocols, with reduced administration time and potentially faster antidepressant efficacy. Objectives: The main aim of this study is to identify MDD endophenotypes/biotypes predictive of response to accelerated treatment of rTMS to better characterize the clinical correlates of response in patients with TRD. Eligibility: Subjects between 18 and 65 years suffering from TRD in stable psychopharmacological treatment for at least one month. Design: This clinical trial includes three phases: 1) a screening phase; a rTMS continued treatment phase; and a follow-up. In order to be enrolled, participants will be screened with: * Medical history to assess the existence of the inclusion criteria and exclude any medical conditions that could contraindicate treatment with arTMS * Questionnaires After being enrolled, baseline data will be collected. In particular, participants will be administered: * Questionnaires * Functional MRI * Cognitive tasks * Eye examination with Electroretinography (ERG) * Blood sampling * Salivary cortisol sampling Repetitive TMS will be delivered during 5 outpatient treatment days (4 times/die). After treatment patients will be contacted by telephone on a weekly basis for the first 3 weeks, to carry out an assessment of the clinical condition. A follow-up visit, in the clinic, will be carried out after 21 days from the last stimulation (Friday), with the administration of psychometric scales. Blood samples will be taken on the first day of stimulation and the day after the last stimulation. Salivary cortisol sampling will be taken before the start of the stimulation protocol, after the first stimulation day and immediately after the last stimulation session foreseen by the protocol. fMRI will be performed during baseline and at the end of treatment. ERG will be performed before the start of the stimulation protocol, after the first stimulation and immediately after the last stimulation session foreseen by the protocol. Patients will undergo ERG again during the follow-up visit at 21 days. Treatment includes: * rTMS: A brief electrical current passes through the coil placed on the head. At each day, participants will receive four rTMS sessions (36 min), with a 55 min interval between sessions. * MRIs: Patients will undergo two MRI sessions lasting 45 min. Blood pressure and respiratory rate will be recorded before the examination. During fMRI, patients will be asked to perform tasks. * Eye examination with Electroretinography (ERG) * Blood and salivary sampling. * Screening tests and questionnaires.

Background: Alcohol Use Disorder (AUD) is a complex psychiatric disorder, involving several brain areas and neurocircuits. Transcranial Direct Current Stimulation (tDCS) allows to stimulate superficial areas of brain using a weak electrical current. Preliminary data suggest that tDCS may reduce alcohol craving and consumption. Objectives: The main outcome is to test if tDCS can reduce alcohol craving and use and to assess the changes in BDNF and pro-BDNF levels. Secondary outcomes are the assessment of other psychiatric dimensions (mood, behavioral and cognitive alterations) associated with prolonged alcohol use. Eligibility: Healthy, right-handed adults ages 18-65 who do have AUD (moderate to severe). Design: This is a randomized, double-blind, sham-controlled study with three phases: 1) a tDCS intensive treatment phase; 2) follow-up with weekly tDCS stimulation; 3) follow-up without tDCS stimulation. Participants will be screened with: * Psychometric Scales * Medical history * Physical exam * Urine tests and breathalyzer * After being enrolled, baseline behavioral and laboratory data will be collected. In particular, participants will undergo: * Psychometric Scales * Venous blood sample (BDNF/proBDNF levels) Participants will be randomized to real or sham tDCS arm. The stimulation will be delivered daily for five days during the first week (intensive treatment phase) and then weekly for 3 months (follow-up with stimulation). During this period patient will be tested with a behavioral and psychometric evaluation.Therefore, participants will receive 3 follow-up monthly visits without tDCS stimulation, in which behavioral and psychometric data will be collected. Treatment includes: * tDCS: The tDCS will be delivered with a stimulator connected to two sponge electrodes, soaked in a saline solution. The stimulation will be administered at a current intensity of approximately 1 mA, for the duration of 20 minutes. The anode will be placed on the right DLPFC, the cathode on the contralateral cortical area. * BDNF/proBDNF levels: A venous blood sample will be collected before the first stimulation and after the last stimulation of the intensive-stimulation period (first week). The blood sample will be centrifuged within 20 minutes of sampling at 1000 × g for 15 minutes. Then, the serum will be aliquoted and stored at -80 ° C until analysis. * Repeat of screening tests and questionnaires * Urine toxicological screen and breathalyzer