Active clinical trials for "Depressive Disorder, Major"

The investigators propose to use low-intensity transcranial focused ultrasound (LIFU), a novel neuromodulation method, to probe the causal involvement of individually defined components of an anteromedial brain circuit in the processing of self-referential thoughts, and the production of repetitive negative thinking (RNT), a prominent transdiagnostic manifestation with adverse clinical consequences. The investigators hypothesize that real vs. sham low-intensity sonication of individually-defined anteromedial structures connecting medial orbitofrontal and anterior cingulate cortices with ventral striatum and anterior thalamus will show reduced initiation or maintenance of RNT as measured by (1) Brief State Rumination Inventory (BSRI) scores and distress associated to repetitive negative thoughts, and (2) improvement of the affective valence associated to self-referential adjectives, and that these changes will be associated with decreased connectivity between structures mentioned above. The present early feasibility study is an initial step that aims to determine its feasibility and help with the planning of a larger study addressed at actual hypothesis testing.

The current study is designed as a prospective partially randomized patient preference (PRPP) trial and recruit psychiatric outpatients or inpatients. Participants who agree to receive randomization will be randomly assigned into a supplementation or placebo group, after stratification for pre-intervention vitamin D status (12-20 ng/mL or <12 ng/mL) and depression status (HDRS-17 ≥ 17 or < 17). Participants who decline randomization but agree to receive follow-up in the observational cohort choose their preferred method (either 4800 IU vitamin D3 per day, or usual care without supplementation). Severity of depression, any change of medication, and side effect will be assessed at baseline and at 2-week intervals for 8 weeks. Serum levels of 25(OH)D, C-Reactive protein (CRP) and 12 cytokines, anthropometrical measurements, dietary intake, physical activity and sun exposure will be assessed at baseline and post-intervention. Additionally, serum levels of 25(OH)D will be assessed at 4 weeks to ensure its safety level.

Patients, physicians, and those who fund depression research are keenly interested in depression treatments that do not involve taking medications. One promising candidate treatment is transcranial direct current stimulation (tDCS), a low-cost technique that involves placing electrodes on specific scalp locations and using a 9-volt battery to cause a small amount of electricity to pass through parts of the brain. Depending on the direction of electrical flow, tDCS can make brain cells (neurons) more likely or less likely to generate their own electrical signals. When evaluated as a treatment, tDCS is typically done in daily sessions over a period of two weeks. One of the challenges of tDCS is to work out the best possible positioning of electrodes and direction of electricity flow to gradually cause lasting changes in brain activity in ways that might be expected to improve depression. To address this challenge, the investigators are using MRI to take pictures of the brain during tDCS. This data will help us better understand the short-term effects of tDCS in depression and help us learn how to customize future treatments to cause a lasting beneficial response. Patients with depression between the ages of 20-55 years are eligible to take part in this research. Potential participants will undergo: An assessment to confirm eligibility. This will take place over a secure videoconference call lasting no more than 3 hours. Two in-person study visits lasting 30 min and 2-1/2 hours respectively. In the first visit, the investigators will use the MRI to take a picture of the brain and head structure to determine appropriate locations for placing the tDCS electrodes at the start of the second visit. Following electrode placement, an MRI scan will be performed to take pictures of the brain during tDCS. Depending on the study arm, Participants may receive 'active' or 'sham' tDCS. The 'sham' condition is identical to the 'active' tDCS in every way except that it involves minimal tDCS and is designed to help rule out effects unrelated to the administered tDCS electricity. Participants may also be asked to perform a mental task during MRI. All participants will be compensated $150 + parking upon completion of all study-visits.

The purpose of this study is to confirm binding of MIJ821 to the NR2B-containing NMDA receptors in the human brain and assess the PC-RO relationship over time using positron emission tomography (PET).

The main purpose of this study is to investigate the effects of ketamine on decision-making and emotion processing in a sample of individuals diagnosed with Major Depressive Disorder (MDD).

Background: Most drugs that treat mood disorders take a long time to work. Ketamine works within hours. A dose can last for a week or more. Certain receptors in the brain might help ketamine work. A drug that blocks these receptors might affect how it works. Objective: To see if the antidepressant response of ketamine is linked to AMPA receptors. Eligibility: Adults ages 18-70 with major depression disorder without psychotic features Design: Participants will be screened under protocol 01-M-0254. They will have blood tests and a physical exam. Participants will stay at the NIH Clinical Center for 5 weeks. Phase 1 lasts 4 weeks. For 2 weeks, participants will taper off their psychiatric medicine. Then they will have the following tests: Blood draws Psychological tests MRI: Participants will lie in a machine that takes pictures of their brain. MEG: Participants will lie down and do tasks. A cone lowered on their head will record brain activity. Optional sleep tests: Electrodes on the scalp and body and belts around the body will monitor participants while they sleep. Optional TMS: Participants will do tasks while a wire coil is held on their scalp. An electrical current will pass through the coil that affects brain activity. For phase 2, on day 0 participants will take the study drug or a placebo orally. While having a MEG, they will get ketamine infused into a vein in one arm while blood is drawn from a vein in the other arm. On day 1, participants will again take the study drug or a placebo orally. On days 3-7, they will repeat many of the phase 1 tests. Days 8 and 9 are optional and include an open label ketamine treatment and many of the phase 1 tests.

This study is a single-blind, multicenter, randomized, controlled crossover trial. The App, developed in South Korea, is an application that provides integrated interventions for stress reduction for the general population. The App provides three contents based on MBSR, CBT, and relaxation sounds that are known to be effective in stress reduction ("Meditation category", "Cognitive approach", and "Relaxation Sound", respectively). Participants (n = 215) recruited via medical practitioner referral will be randomized to App first group (fAPP) or a waitlist crossover group (dAPP). Inclusion criteria are age 19-65; diagnosed with mild to moderate major depressive disorders (Score of 7-24 on the Hamilton Rating Scale for Depression); Stable medication for 28 days prior to study participation. The study was conducted over eight weeks, the fAPP group used The App for the first four weeks and the dAPP group for the next four weeks, and during all study periods, the participants received usual pharmacological treatment. Primary outcome measures are the Depression Anxiety Stress Scale-21. The analysis will use mixed-model repeated measures.

Ketamine's efficacy as an antidepressant is now well established yet the mechanisms underlying its antidepressant effect are yet to be fully described. Work in the animal literature and research in humans is suggestive of specific effects on anhedonia and memory reconsolidation. In this study the investigators will further explore the effects of ketamine on learning and memory as well as measuring the associated changes at neural level in a sample of healthy volunteers. Participants will be assigned to receive ketamine or placebo and complete a set of tasks which will allow the investigators to quantify the effect of ketamine on learning about reward and punishment and memory for learned reward associations 24 hours after ketamine infusion. This study will help the investigators to understand the basis of ketamine's antidepressant effects and aid the development of new treatments for depression.

The purpose of the study is to investigate a short-term treatment option for major depressive disorders by administering nitrous oxide gas. At this time, the main purpose is to complete a feasibility study with 40 participants suffering from treatment-resistant depression. Participants will be randomized to (1) Study group: Nitrous oxide (inhaled) + solution of saline (injected) and the (2) Control group: Oxygen (inhaled) + Midazolam (injected) as an Active Placebo.

Joiner's interpersonal theory of suicide postulates that the wish of death comes from feelings of perceived burdensomeness and thwarted belongingness. But, only people who have acquired the capability to kill themselves will attempt suicide. The acquired capability refers to a reduction of fear to death, and a higher pain tolerance. Indeed, to commit suicide involves to endure pain during the act. Thus, higher pain tolerance seems to be a necessary feature for suicidal act. Past studies have shown higher pain threshold and tolerance in suicidal patients, whatever the stimulus was (electric, thermic or mechanical), compared to patients without suicide history. Moreover, Caceda and colleagues demonstrated higher pain threshold in recent suicide attempters (suicidal act within 72h) compared with depressed patients. Five days after the initial evaluation, pain threshold of recent suicide attempters decreased to be similar to depressed patients with suicidal ideation. Therefore, it may exist a specific state during which the pain tolerance is increased. During this "hypoalgesic state" patients with suicidal ideation could attempt suicide to get relief from suffering. However, little is known about the specific mechanisms that are responsible for the higher pain threshold and tolerance in suicide attempters. Pain is a dynamic system that results from excitatory and inhibitory messages. The modification of one of these mechanisms could explain the higher tolerance in recent suicide attempters. Three of them are of particular interest: The conditioned pain modulation (CPM) is a modulatory pain mechanism. CPM works through descending pathway that reaches the spinal cord and modulates pain processing from the first nociceptive synapse.In recent suicidal patients, an increase of the CPM could explain higher pain tolerance. The "wind-up" mechanism is defined as the highest excitability of the second order nerve. Even if the stimulus remains stable, pain continuously raises. In recent suicide attempters, a reduction of this mechanism could explain higher pain tolerance. The threshold of Aδ and C nociceptors. If a nociceptive fiber is less excitable than the other, it would explain higher pain threshold.