Active clinical trials for "Depressive Disorder, Major"

This study is designed to look at that involvement of a process in the brain called the glutamate system in depression. Participants will undergo a screening session, up to two functional Magnetic Resonance Imaging (fMRI) scans, and up to three Positron Emission Tomography (PET) scans, as well as cognitive testing at each scan session. For one of the PET scans, a drug (either ketamine or n-acetyl cysteine) will be administered. Hypothesis 1: The investigators hypothesize administration of ketamine or n-acetylcysteine (NAC) will lead to a decrease in mGluR5. Hypothesis 2: The investigators hypothesize an improvement in memory and attentional skills after drug challenge. Hypothesis 3: The investigators hypothesize an increase in mGluR5 availability and change in MRI measures post drug challenge as compared to baseline, signifying synaptogenesis. Hypothesis 4: We expect there should not be a significant difference in reduction in mGluR5 availability due to differences in ABP688 radiotracer infusion.

This study aims to improve understanding of how people with low mood and negative feelings (known as dysphoric) may be different from people with normal mood and feelings (nondysphoric) when responding to a variety of social and emotional information. The study will look at the patterns of activity in peoples' brains in situations (presented as a battery of tests) after treatment with a medicine (escitalopram) or a placebo. The results from this study will help to gather information about the effectiveness of the various tests being used in this study in detecting any changes due to treatment with an antidepressant. Half the volunteers taking part in this study will be dysphoric (mildly depressed) whilst the other half of volunteers will be healthy volunteers. It is hoped that the results of this study will provide guidance for assessing effectiveness of new medicines and potentially help with the treatment of depression.

This is a study to assess the distribution, metabolism and excretion of [14C]AZD6765 after a single-dose intravenous administration.

This study involves collaboration between McLean Hospital, Geriatric Medicine at the Cambridge Health Alliance (CHA) and other sites within the Partners and Harvard Medical School network. The investigators plan to recruit individuals 55 to 89 years old with treatment resistant depression. Someone with "treatment resistant" depression for this study may be someone who still has sad or low feelings and thoughts even though he/she is taking an antidepressant medication for at least 8 weeks to help relieve his/her depression. During the study, subjects will gradually add memantine hydrochloride in dosages up to 20 mg/day for 8 weeks to their standard antidepressant treatment. The investigators are doing this research study to help answer 3 questions: Do older adults with treatment resistant Major Depression have lower levels of a chemical in the brain called NAAG than older adults without Major Depression? Do older adults with naturally low NAAG levels do better on memantine hydrochloride treatment than older adults with higher amounts of this chemical on memantine hydrochloride treatment? Do older adults with treatment resistant depression have more problems with memory and concentration than older adults without depression? The investigators are also interested in looking at electrical and neuronal activity of the brain, spiritual beliefs, and fatigue in relationship to depression. The investigators hypothesize that: Older individuals with treatment resistant Major Depression will have lower levels of NAAG compared with age-matched older control subjects. Older adults with treatment resistant depression and low NAAG levels will do better on treatment with memantine hydrochloride than older adults on memantine with higher NAAG levels. Older adults with depression will do better on tests of attention and executive functioning after treatment with memantine hydrochloride. Healthy controls will do better on tests of attention and executive functioning than older adults with depression.

Aripiprazole has been approved by the FDA for augmenting ineffective/partially effective oral antidepressant therapy in patients suffering from major depression. The mechanism by which this augmentation is achieved is not known. This study has been designed to test the hypothesis that the primary mechanism of action of aripiprazole (ARP) antidepressant augmentation is through the dopaminergic pathway. Two positron emission tomography (PET) scan procedures and a functional magnetic resonance imaging (fMRI) scan will be used to test this hypothesis.

The purpose of this study is to determine whether Integrated Cognitive Behavioral Therapy or Twelve Step Facilitation Therapy is most effective for treatment of dually diagnosed veterans with depressive and substance use disorders.

The primary purpose of this study is to investigate neural mechanisms and predictors of treatment outcome in Mindfulness-Based Cognitive Therapy (MBCT) for recurrent Major Depressive Disorder.

Purpose: Investigating the effects of non-invasive transcranial alternating current stimulation (tACS) on healthy participants and participants with mood disorders. Participants: 40 males and females, ages 18-65, with depressed mood; 40 healthy males and females, ages 18-65, free of neurological or psychiatric conditions. Procedures: This is a single visit study with two stimulation conditions (tACS and sham tACS). The session will begin with clinical assessments (including confirmation of diagnosis), followed by an interactive EEG task, then a 7 minute resting state EEG (2 minutes eyes closed, 5 minutes eyes open), followed by the stimulation session (40 minutes of tACS or sham tACS), followed by an additional 5 minute resting state EEG. The stimulation will involved 40 minutes of transcranial alternating current stimulation, 2 mA in amplitude and at individualized alpha frequency (determined by the 2 minutes eyes closed EEG recording; between 8 and 12Hz).

The aim of the project is to establish a multimodal imaging approach for the investigation of the neural mechanisms underlying neuroreceptor regulation, glutamatergic metabolism and brain function that are of particular relevance for major depressive disorder (MDD) and that can be translated into clinical applications. There is growing evidence for imbalance with regard to glutamatergic neurotransmission in stress-related affective disorders. Further support for the hypothesis that dysfunctional glutamatergic signaling underlies major depressive disorder, and indeed that its reversal constitutes a potential efficacious mechanism of action, is provided by the evidence that pharmacological compounds active at the N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor such as ketamine exert rapid antidepressant effects. As a tool compound ketamine enables the safe investigation of the brain region-specific effects of NMDA receptor antagonism in terms of glutamatergic neurotransmission, brain function and the association of these neural changes with emotional state, thereby allowing for increased understanding of the therapeutic mechanism of action. The possibility to simultaneously study brain perfusion (arterial spin labeling), functional brain activity (fMRI) and connectivity (resting state fMRI), neurometabolism (proton magnetic resonance spectroscopy) and metabotropic glutamate receptor densities (positron emission tomography) will unravel their functional interplay in the mechanisms underlying the regulation of mood and cognition. Combining those imaging modalities with treatment interventions in healthy subjects and depressed patients, this project aims at providing insight into the neuropharmacological effects of ketamine and its antidepressant properties.

The aim of this project is to determine whether the acute oral administration of Ibuprofen changes the activation pattern in the amygdala and other brain structures during functional magnetic resonance imaging. The investigators use a double-blind, randomized, repeated-measures design. Each of the 20 healthy control subjects will be tested three times and receive placebo, 200 mg or 600 mg dose of ibuprofen p.o. The study will consist of 4 sessions: a baseline screening session and 3 testing sessions scheduled 1-2 weeks apart. Each of these individuals will undergo a multi-level assessment based on the RDoC approach that consists of (a) a standardized diagnostic assessment, (b) self-report questionnaires assessing the positive and negative valence domains as well as interoception, (c) behavioral tasks assessing reward-related processing, avoidance, and aversive processing, cognition, and interoception; (d) physiological measurements consisting of facial emotion expression monitoring, heart rate and respiration, (e) functional magnetic resonance imaging focusing on reward-related processing, fear conditioning and extinction, cognitive inhibition, and interoceptive processing, and (f) biomarker assessments.