Selfemra

This randomized 2x2 factorial intervention trial administers 8 weekly cognitive behavioral therapy (CBT) sessions (yes/no) and 4 bi-weekly active whole-body hyperthermia (WBH) sessions (yes/no) to adults aged 18 years or older with major depressive disorder (MDD).

Many people with depression do not get better with standard treatments like medications or talk therapy. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation treatment that uses magnetic pulses to stimulate areas of the brain involved in depression. One form of TMS called intermittent theta burst stimulation (iTBS) is FDA-cleared for depression and takes only 3 minutes to deliver. However, about one-third of patients do not respond to iTBS, and another one-third do not reach full remission. Improving iTBS requires a better understanding of how it works in the brain. iTBS is thought to work by strengthening connections between brain cells, a process called synaptic plasticity. This process depends on a type of brain receptor called the NMDA receptor. Most of what researchers know about how iTBS affects these connections comes from studies of healthy people. It is not known whether iTBS works the same way in the prefrontal cortex - the brain region targeted during depression treatment - or in people who actually have depression. This study has two phases. In Phase 1, both healthy volunteers and people with depression will complete 4 research visits to test how iTBS changes brain activity in the prefrontal cortex and whether medications that increase or decrease NMDA receptor activity change those effects. Each visit involves active or sham (inactive) iTBS combined with one of three study medications: a placebo (inactive pill), d-cycloserine (a medication that increases NMDA receptor activity), or dextromethorphan (a medication that decreases NMDA receptor activity). Brain activity is measured before and after each TMS session using electroencephalography (EEG), a painless test that records electrical signals from the scalp through a cap placed on the head. All participants also complete a brain MRI before beginning study visits for targeting purposes. In Phase 2, participants with depression will be offered a standard clinical course of 30 daily iTBS sessions (Monday through Friday over 6 weeks). Each session is combined with one blinded study medication (placebo, d-cycloserine, or dextromethorphan) taken daily. Brain activity measurements and standard depression and anxiety questionnaires are collected weekly throughout this phase to track how the brain changes over the course of treatment and whether those changes relate to improvements in symptoms. Together, the two phases of this study aim to identify the brain mechanism by which iTBS works in people with depression. This knowledge could lead to more effective TMS treatments for people who have not responded to medications or other therapies.

A Phase 3 Double-blind, Placebo-controlled Study (Part A) with an Open-label Extension (Part B) Evaluating DT120 Compared to Placebo in Major Depressive Disorder - Ascend

Depression is the leading cause of disability worldwide, affecting an estimated 300 million people. Despite available treatments, response rates remain modest, and treatment resistance is common. Novel treatments are needed that act rapidly, produce lasting effects and work differently than existing antidepressants. In clinical trials, psilocybin has shown promise as a treatment for depression due to its rapid onset of antidepressant effects and sustained benefits. This study will use MRI scanning of the brain and other biological measures (biomarkers) to investigate how psilocybin affects brain activity and psychological flexibility before, during, and after receiving psilocybin in participants with depressive symptoms.

The goal of this study is to understand why certain treatments help people reduce repetitive negative thinking (RNT), which is common in many mental health problems. We want to: 1. Figure out what actually causes repetitive negative thinking to decrease when people use cognitive-behavioral therapy (CBT). 2. Find out which parts of RNT-focused CBT are the most important - the parts that truly make a difference in reducing RNT. The main result we will look at is how much a person's repetitive negative thought patterns change from the start of the study to the end of treatment (16 weeks). We will measure this using the Perseverative Thinking Questionnaire at baseline and week 16.

The purpose of this study is to determine whether changes in sleep consolidation occur during home-based transcranial direct current stimulation (tDCS) in adults with moderate depression and whether these changes are temporally associated with improvements in depressive symptoms.

The goal of this clinical trial is to learn whether brain scan results can help predict and track changes in obsessive-compulsive disorder, or OCD, symptoms in children and teens ages 10 to 17 who receive Exposure and Response Prevention therapy, also called ERP. ERP is a type of therapy in which participants practice facing OCD-related fears while resisting rituals or compulsions. The main question this study aims to answer is: Can each participant's pattern of brain connections, measured with functional MRI brain scans, help predict and track weekly changes in OCD symptoms during and after a 14-week course of ERP, including during planned monthly booster sessions and additional booster sessions offered if symptoms worsen? All participants will receive ERP. There is no placebo and no comparison group. Participants will: * Complete screening, consent or assent, interviews, questionnaires, and MRI safety checks * Receive 14 weekly ERP sessions * Complete OCD symptom assessments and functional MRI brain scans before, during, and after ERP * Receive planned monthly ERP booster sessions after the 14 weekly sessions * Receive additional brief ERP booster sessions if OCD symptoms worsen during follow-up * Take part for up to about 62 weeks

This study will seek to determine the (1) acceptability and (2) feasibility of psilocybin as an adjunct to cognitive-behavioral therapy, delivered as a group treatment (G-PACBT) for major depressive disorder and (3) explore the clinical effects of G-PACBT on depressive symptoms and psychosocial functioning.

Canada has one of the highest rates of multiple sclerosis (MS). MS patients experience disabling motor, visual, and sensory symptoms, and a high risk of comorbid major depressive disorder (MDD) and severe fatigue. The lifetime prevalence of MDD in MS patients is about 50%, and nearly 90% experience severe fatigue, both of which are not responsive to typical treatments. Repetitive transcranial magnetic stimulation (rTMS) is a first line, Health Canada approved non-invasive neurostimulation treatment for MDD. rTMS induces electrical activity in the cortex using magnetic fields generated outside of the head to drive neuronal firing in the target site. However, MS is typically an exclusion criterion due to safety concerns. The goal of this clinical trial is to learn if repeated transcranial magnetic stimulation (rTMS) can be used to treat depression symptoms in adults with multiple sclerosis (MS). rTMS is a non-invasive form of brain stimulation that uses magnetic pulses to stimulate specific parts of the brain. The main questions it aims to answer are: Is rTMS safe, tolerable, and feasible to deliver as a treatment for depression and fatigue symptoms in individuals with MS? Does rTMS show preliminary effectiveness in improving depression and fatigue symptoms in this population? Researchers will determine whether rTMS treatment improves mood, fatigue, and cognition across time points (baseline, after treatment, and 4-week follow-up). Participants will: Complete screening, questionnaires, clinical assessments, cognitive tests, a brain MRI to help tailor the TMS treatment, and receive daily TMS sessions for 5 consecutive days, including: Pre-TMS brain mapping, five rTMS treatments (3 minutes) per day, separated by one hour. A safety and tolerability questionnaire will be administered daily. Complete post-treatment assessments (questionnaires, cognitive tests, psychiatric evaluation). Complete a 4-week follow-up visit, in person or virtually. Wear a fitness tracking watch during the study so researchers can collect activity data remotely. About 20 people will take part in this study through the University of Calgary.

The goal of this clinical trial is to improve how electroconvulsive therapy (ECT) stimulation settings are chosen. Researchers will use real-time brain monitoring to measure both seizures and a recently identified brain event called cortical spreading depolarization (CSD). The main questions it aims to answer are: What is the best way to increase ECT stimulation settings? How do different pulse settings affect the brain's response? Can certain settings produce CSD without causing a seizure? Participants already receiving ECT as part of their care will take part. They will be assigned to one of two groups: Index ECT group: Participants starting ECT will receive different standard titration approaches. Maintenance ECT group: Participants receiving ongoing ECT will undergo a brief, low-dose stimulation test before treatment. All participants will be monitored using brain physiology (EEG and blood flow) and symptom scales during treatment.

Many people with depression do not get better with standard treatments like medication. One promising alternative is transcranial magnetic stimulation (TMS), a non-invasive procedure that uses magnetic pulses to stimulate specific brain regions. A particular pattern of TMS called continuous theta-burst stimulation (cTBS) is thought to reduce overactive brain activity in depression, but the investigators do not yet fully understand how it works at the level of brain cells and connections. This study aims to determine the biological mechanism by which cTBS changes brain activity in people with depression. Specifically, the investigators are testing two competing ideas: (1) that cTBS works by weakening the connections between brain cells through a process called long-term depression (LTD), which is driven by a chemical messenger system called glutamate; or (2) that cTBS works by increasing the brain's natural "braking" system, driven by a different chemical messenger called GABA. To test these ideas, participants with depression will receive cTBS along with one of four FDA-approved medications, or placebo, that either boost or block these chemical messenger systems. The investigators will measure changes in brain activity using electroencephalography (EEG) recorded simultaneously with TMS. Specific patterns in the EEG signal, called TMS-evoked potentials (TEPs), act as a window into how different brain cell types are responding to stimulation. Each participant will complete four study visits, each testing a different drug-TMS combination in random order. One group of participants will test drugs targeting the glutamate system (d-cycloserine and memantine). A second group will test drugs targeting the GABA system (lorazepam and baclofen). All drugs are given as a single oral dose and are commonly used in clinical practice. Understanding exactly how cTBS works at a biological level could open the door to more effective, personalized TMS treatments.

The goal of this clinical trial is to determine if alpha phase-locked auditory stimulation can improve sleep in people with insomnia and depression. The main goals of the pilot study are the following: Determine whether alpha phase-locked auditory stimulation (active stimulation) improves objective and subjective sleep in individuals with insomnia and depression. The study team hypothesizes that active auditory stimulation will reduce objective and subjective sleep onset latency (SL) and wake after sleep onset (WASO) compared to a sham stimulation. Participants will: * Wear Elemind Neuromod headband nightly for 4 weeks (1 week baseline, 1 week active/sham stimulation, 1 week washout, and 1 week opposite condition - active/sham stimulation) * Wear actigraphy watch for duration of the study * Complete questionnaires regarding their sleep, mood, and satisfaction with the device