View clinical trials related to Depressive Disorder, Major.
Filter by:This project is designed to examine the role of the subgenual anterior cingulate cortex (sgACC) in anhedonia and anxiety in humans with depression, as well as the acute and sustained effects of ketamine on agACC activation and depression symptoms.
This study will apply a comprehensive tools that integrates neuroimaging, psychological evaluation, and sleep monitoring through 18F-MPPF PET/MR, neuropsychological tests, and polysomnography (PSG) to explore the neurobiological mechanisms underlying transcranial alternating current stimulation (tACS) for depressive disorders, mainly focusing on the serotonergic system revealed by Serotonin-1A (5-HT1A) receptor.
Major depressive disorder (MDD) is a chronic mental illness, with 60% lifetime risk of recurrence after the first MDD episode. Despite available treatment options for MDD, only about half to two-thirds of patients respond to first-line antidepressant treatment, and only 30% to 45% of patients achieve remission. Scholars assume that this low remission rate and high rate of treatment resistance are due to the polyetiological nature of the disease, the heterogeneity of the clinical picture of depression, and the lack of biomarkers to stratify MDD subtypes. The aetiology of MDD, although researched extensively, remains unclear. None of the known mechanisms alone explains the pathogenesis of depression, meaning that the interplay of several factors contributes to the development of MDD. Accumulated scientific evidence has supported the importance of the immune system in the etiopathogenesis of MDD. Until now, the cause of the low-grade inflammation observed in this subgroup of MDD patients has been unclear. In the proposed study, the investigators will test a new hypothesis of the immune theory of the development of MDD: the endotoxin hypothesis of neurodegeneration. This hypothesis states that endotoxin, causes or contributes to neurodegeneration. Blood plasma levels of LPS are normally low but are elevated during infections, gut inflammation, gum disease, and neurodegenerative diseases. Dysbiosis may promote increased intestinal permeability ("leaky gut"), which leads to bacterial translocation across the intestinal barrier and into the circulation, thus forming of LPS and LPS-binding protein complex, which triggers the secretion of cytokines. Data suggest that LPS-induced peripheral inflammation can activate neuroinflammation. However, it is not known whether a low-level persistent presence of LPS in the circulatory system can cause low-grade chronic neuroinflammation leading to neurodegeneration and/or symptoms of MDD. Based on existing preclinical and clinical research data, the investigators hypothesise that an increase in blood plasma endotoxin and peripheral cytokines induce BBB dysfunction, neuroinflammation and neurodegenerative processes in specific etiologically relevant structures of the brain and cause clinical manifestation of depressive symptoms and cognitive damage. In this study the investigators are also going to investigate the effects of single nucleotide polymorphisms of four genes in relation to blood plasma endotoxin and peripheral cytokines concentrations and clinical manifestation of MDD.
The study aims to examine inter-brain synchrony between patients and therapists over the course of psychotherapy. Twenty patients will undergo a 16-session course of psychotherapy for major depressive disorder. The protocol used will be supportive-expressive psychotherapy (see Luborsky et al., 1995). Participants will also undergo Hamilton depression interviews a week before treatment, before every session and a week after treatment. functional near-infrared spectroscopy (fNIRS) imaging will be used to record brain activity during every other session (sessions 1, 3, 5, 7, 9, 11, 13, 15) as well as during interviews at baseline, on session 8 and at followup. Saliva samples will be collected during the same sessions to measure hormone and cytokine levels during the same sessions. Participants completed questionnaires before and after the study, and before and after each session. The researchers hypothesized that synchrony will gradually increase over the psychotherapy sessions, and that synchrony in the pre-treatment interview will be lower than in the post-treatment interview.
Anhedonia is a core feature of major depressive disorder (MDD) (DSM-5). Functional magnetic resonance imaging (fMRI) studies have associated anhedonia in MDD with altered frontostriatal activity and functional connectivity relative to controls. Conversely, antidepressant treatment is associated with increased ability for patients with MDD to sustain frontostriatal activity in a manner predictive of decrease in anhedonia and gains in daily positive affect. Novel interventions are needed to address anhedonia. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has been shown to activate striatal reward circuits. Positive Affect Treatment (PAT) was developed to treat deficits in reward processing; a critical skill patients are trained on in PAT involves recounting and savouring of positive experiences. However, amotivation impedes some patients from engaging in positive activities, prompting the development of virtual reality reward training (VR RT) for this skill. Evidence is building that brain state at the time of rTMS impacts its therapeutic effect. For example, imaginal exposure and individualized symptom provocation just prior to rTMS enhances its therapeutic effect on post-traumatic stress disorder and obsessive-compulsive disorder, respectively. It is unknown whether VR RT can augment rTMS for MDD and if so whether it is mediated by enhancing changes in frontostriatal activity or functional connectivity. The current study is significant for multiple reasons. As mentioned, there is a paucity of effective treatments for anhedonia and this study may inform development of a novel treatment strategy that harnesses findings from affective neuroscience. Recent economic analysis suggests that rTMS can be more cost-effective than pharmacotherapy or ECT for treatment-resistant depression (Ontario Health, 2021). Our findings will provide insight on ways to synergize specific psychotherapeutic techniques with targeted stimulation of brain circuits to more effectively treat subtypes of depression.
The aim of this study is to identify biologically viable targets for the treatment of major depressive disorder (MDD) and anxiety disorder (AD) with the ultimate goal of guiding physicians' therapeutic strategies and identifying more effective and safer treatments for patients. Following the inclusion and exclusion criteria, the investigators will recruit 10 patients with a diagnosis of anxious-depressive disorder (MDD-AD) and 10 healthy controls (HC) subjects. Each participant will be evaluated by a team of expert psychologists and physicians, who will be conducting a structured interview and administering a set of psychopathological scales to assess the symptoms' severity. The participants will also undergo7T multimodal neuroimaging session (including T1-weighted, 1H-MRS and fMRI). In the second part of the study, murine models will be used to study the role of integrin β3 (Itgb3) and protocadherin 9 (Pcdh9) in glutamatergic transmission at a molecular level and to evaluate whether the electrophysiological and behavioral defects identified in Itgb3- and Pcdh9-knockout mice can be restored by CRISPR-mediated transcription activation (CRISPRa).
Major Depressive Disorder (MDD) is a very common illness that is usually treated with antidepressant medication. Depression can be caused by many things such as childhood experiences, genetics, and changes in the way the body and brain function. For those with depression where medication and psychotherapy have limited benefit, repetitive transcranial magnetic stimulation (rTMS) is an effective treatment. rTMS is a treatment that involves stimulating certain areas of the brain with magnetic field pulses. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region. This can be helpful in treating some kinds of psychiatric and neurological disorder, including MDD. It is not fully known how rTMS changes brain activity to improve symptoms of depression. However, certain brain areas responsible for behaviours impacted by depression are underactive in those with depression. One of those brain regions called the dorsolateral prefrontal cortex (DLPFC), and the investigators will target this region using rTMS. By increasing the activity of these regions, rTMS could potentially improve depression symptoms. For participants receiving rTMS, the investigators will be using the participant's brain scan to better understand brain activity of the brain region stimulated by rTMS before and after treatment. In this study, the investigators will be collecting detailed information about participants' psychiatric history and depression symptoms, as well as brain scans and saliva samples. The saliva samples will undergo proteomic (having to do with proteins) analyses to identify biological markers ("biomarkers": biological features (e.g.: gene, protein) that can be measured to indicate factors related to rTMS response. The investigators' goal is to use this information to help us understand whether improvement to rTMS depends on brain activity or proteomic factors localized to two specific behaviours impacted by depression: reward processing and working memory (the capacity to hold information temporarily, such as holding a person's address in mind while listening to instructions about how to get there).
Major Depressive Disorder (MDD) is a very common illness that is usually treated with antidepressant medication. Depression can be caused by many things such as childhood experiences, genetics, and changes in the way the body and brain function. It is most likely caused by a combination of several of these factors. The prevalence of suicide attempt in Major Depressive Disorder (MDD) is about 20%. Risk for suicide attempt can be increased by many things such as negative life events, genetics, and changes in the way the body and brain function. It is most likely caused by a combination of several of these factors. In this study, the investigators will be collecting detailed information about participants' psychiatric history and depression symptoms, as well as brain scans. The goal is to use this information to help us determine what predicts suicide attempt history.
Optimizing treatments in mental health requires an easy to obtain, continuous, and objective measure of internal mood. Unfortunately, current standard-of-care clinical scales are sparsely sampled, subject to recency bias, underutilized, and are not validated for acute mood monitoring. The recent shift to remote care also requires novel methods to measure internal mood. Recent advances in computer vision have allowed the accurate quantification of observable speech patterns and facial representations. The continuous and objective nature of these audio-facial behavioral outputs also enable the study of their neural correlates. Here, the investigators hypothesize that video-derived audio-facial behaviors have discrete neural representations in the limbic network and can provide a critical set of reliable longitudinal estimates of mood at low cost across home and clinic settings.
In this triple-blind randomized controlled trial, we ask if targeting intermittent theta burst stimulation (iTBS) based on individual resting state connectivity improves treatment outcomes in major depressive disorder (MDD). For the trial, we will recruit 210 patients with major depressive disorder. Each patient will undergo a 30-40-minute MRI scan, after which they will receive a 6-week standard iTBS treatment. Participants will be randomized to receive iTBS either to the standard neuronavigated target (a technique for treatment location targeting, based on group-average connectivity) or to a personalized connectivity-guided target selected based on individual functional connectivity scans. The main outcome of this trial is response rate as determined by ≥ 50% reduction in Grid HRSD-17 scores. Secondary outcomes include remission rate, change in depression, anxiety and anhedonia symptoms, quality of life, and biological measures of heart rate variability, objective sleep measures and daily activity as a proxy of anhedonia - defined as a reduced ability to experience pleasure.