
rTMS in Alleviating Pain and Co-Morbid Symptoms in Gulf War Veterans Illness (GWVI)
Gulf War IllnessDepressionThis study aims to look at the effectiveness of using repetitive transcranial magnetic stimulation (rTMS) in relieving pain and other co-morbid symptoms of Gulf War Illness.

RCT Comparing EMDR and CBT for Treatment of Resistant Depression
Eye Movement Desensitization and ReprocessingCognitive Behavioral Therapy5 moreDepression is one of the most common invalidating mental disorders, ranked by World Health Organization as the single largest contributor to global disability. Current recommended treatments for depression include antidepressant medication and according to guidelines, Cognitive Behavioral Therapy (CBT) and Interpersonal Therapy (IPT). Despite encouraging preliminary results (e.g., Matthijssen et al., 2020), Eye Movement Desensitization and Reprocessing (EMDR) therapy is not yet recognized as an effective therapy for depression by APA and NICE. The project aims to conduct a large multisite study that addresses the shortcomings of previous efficacy research on EMDR for depression. The primary aim is to evaluate the effectiveness of EMDR therapy in reducing depressive symptoms in adults with major depression as compared to CBT. Secondary aims of the study are the effectiveness of EMDR, as compared to CBT and TAU, in improving anxiety, and other symptoms. It is hypothesized that EMDR is not inferior to CBT.

A Randomized Controlled Study of Digitalized Cognitive Behavioral Intervention for Antenatal Depression...
DepressionAntenatal DepressionThe main objective of the current research project is to evaluate the effectiveness of the digitalized cognitive behavioral therapy program including telephone coaching for antenatal depressive symptoms. The participants are screened from the general population of pregnant women, as a part of the routine maternity health care check-ups. Mothers with depressive symptoms will be randomized into intervention group receiving guided digitalized treatment program or control group receiving education material about depression in digital form.

Scopolamine in Bipolar Depression
Bipolar Disorder DepressionThis is a single-site, randomised, double-blind, placebo-controlled, parallel, phase IIb clinical trial. The primary objective of the SCOPE-BD study is to investigate the efficacy and safety of IV Scopolamine, compared to placebo, in reducing severity of depression in individuals with bipolar disorder who are experiencing a depressive episode of at least moderate severity

Efficacy of Convulsive Therapies for Bipolar Depression
Bipolar DisorderBipolar Depression2 moreThis trial aims to assess the efficacy and tolerability of Magnetic Seizure Therapy (MST) as an alternative to electroconvulsive therapy (ECT) for Bipolar Disorder (BD). Research indicates that the prevalence of treatment resistance in bipolar depression is twice that of unipolar depression. The limited effectiveness of current treatments for bipolar depression coupled with the medical and economic burden associated with the disorder engenders a need for novel therapeutic interventions that can provide greater response and remission rates.

Post-Stroke Optimization of Walking Using Explosive Resistance
StrokeDepressionThe investigators will study the effects of a 12 week strength training program on individuals who have had a stroke and are depressed to see if this type of exercise training helps treat depression and improves walking function. Our goal is to use the information collected in this study to help design treatments for people who have had a stroke that will help with many of the common consequences of stroke, including depression, muscle weakness and slow walking. Progress toward overcoming some of these issues would be incredibly valuable to any person who has had a stroke and their families.

Transcranial Magnetic Stimulation for Psychological Distress in Patients With Advanced Illness
Depressive SymptomsDepression3 morePsychological and existential distress are a common cause of suffering among patients nearing the end of life, and a major reason for requesting medical aid in dying. Existing treatments for psychological and existential suffering have low efficacy and are challenging to use in a palliative context. There is a need to develop scalable, brief, and rapidly effective therapeutic approaches that can reduce psychological and existential distress in patients nearing the end of life. Repetitive Transcranial Magnetic Stimulation is an effective treatment for refractory depression, and new protocols and increasing availability of rTMS may make this therapy feasible and acceptable for patients who suffer from psychological or existential distress near the end of life. Among patients with advanced illness followed by a PC provider, the study objectives are to: Identify the lowest and range of therapeutic rTMS dose to relieve psychological distress, including an analysis of clinical predictors of response. Test the feasibility and preliminary efficacy of rTMS for the treatment of psychological distress including: 1) ease of recruitment; 2) completion of follow-up; 3) effect size and variance estimates of treatment for primary and secondary outcomes; and 4) patient satisfaction with treatment. This study is a phase 2a dose-finding open-label clinical trial, followed by a phase 2b prospective, sham-control or sham-crossover study, depending on the therapeutic dose identified in phase 2a. The investigators will enroll eligible patients from an inpatient palliative care unit and administer rTMS according to established best practice international guidelines. Two screening tests will be conducted (one completed by patient and another by the treating physician) to ensure the patient has no contraindications to rTMS. In the open-label dose-finding study, investigators will determine the appropriate dose of treatment that leads to positive patient outcomes, assess characteristics associated with positive and rapid response to rTMS, and examine if this treatment is feasible and acceptable to patients by measuring rates of enrollment and completion of the treatment sessions. Based on results from this first phase, a phase 2b feasibility and preliminary efficacy randomized clinical trial will be conducted to measure the effect of rTMS by comparing patient symptoms before and after the rTMS intervention.

A Novel Use of a Sleep Intervention to Target the Emotion Regulation Brain Network to Treat Depression...
InsomniaDepressionSeveral lines of evidence suggest that unhealthy sleep patterns contribute to depressive symptoms through disruption of brain networks that regulate emotional functions. However, we do not yet know to what degree the emotion regulation brain network is modified by the restoration of sleep, or whether the degree to which a sleep intervention modifies these neural targets mediates reductions in other depressive symptoms including suicidality. The overall aim is to test the efficacy of an established sleep intervention (Cognitive Behavioral Therapy for Insomnia (CBT-I)) in reducing depressive symptoms through improving emotion regulation brain function in individuals with elevated depressive symptoms and clinically meaningful sleep disturbance. In this study, we will assess feasibility of recruitment and retention as well as target engagement. Target engagement is defined as the treatment effect on increasing mPFC-amygala connectivity, and/or decreasing amygdala reactivity during emotion reactivity and regulation paradigms. Participants will be 70 adults experiencing at least moderate sleep disturbances and who also have elevated anxious and/or depressive symptoms. Emotion distress and sleep disruption will be assessed prior to, and weekly while receiving six Cognitive Behavioral Therapy for Insomnia (CBT-I) across a period of 8 weeks. CBT-I improves sleep patterns through a combination of sleep restriction, stimulus control, mindfulness training, cognitive therapy targeting dysfunctional beliefs about sleep, and sleep hygiene education. Using fMRI scanning, emotion regulation network neural targets will be assayed prior to and following completion of CBT-I treatment.

The Effects of Light Therapy to Treat Cancer-related Side Effects
Breast CancerCircadian Rhythms5 moreSevere fatigue, depression, sleep problems and cognitive impairment are the most commonly reported side effects of cancer treatment. These aversive side effects are hypothesized to be related to the disruption of circadian rhythms associated with cancer and its treatment. Exposure to Bright White Light (BWL) has been found to synchronize the circadian activity rhythms but research with cancer patients has been scarce. Therefore, the proposed randomized control trial (RCT) will test if systematic light exposure (sLE) will minimize overall levels of cancer-related fatigue (CRF), depression, sleep problems and cognitive impairment among breast cancer patients undergoing breast cancer treatment (i.e., surgery, chemotherapy). SLE incorporates the delivery of harmless UV-protected BWL or Dim White Light (DWL - standard comparison in light studies) delivered to patients by using special glasses for 30 minutes each morning, during their treatment. The proposed study, including a delineated comparison condition, will investigate the effects of BWL on CRF, sleep, depression, cognition, circadian rhythms, and inflammation markers among patients undergoing breast cancer treatment. The proposed RCT could have major public health relevance as it will determine if an easy-to-deliver, inexpensive, and low patient burden intervention reduces common side effects (e.g., CRF, depression, cognitive impairment) of cancer treatment (i.e., surgery, chemotherapy). Aim 1 - Assess whether Bright White Light (BWL) compared with Dim White Light (DWL) among breast cancer patients undergoing breast cancer treatment will minimize overall levels of CRF, depression, sleep problems, and cognitive impairment during and after breast cancer treatment, compared to healthy controls. Aim 2 - Determine whether the BWL intervention affects cortisol rhythms, circadian activity rhythms, melatonin rhythms, and inflammation markers that have been identified as correlates/causes of cancer-related side effects (e.g., CRF, depression, sleep problems). Aim 3 - Exploratory: Explore whether the effects of BWL compared to DWL on the cancer-related side effects (e.g., CRF, cognitive impairment) are mediated by the beneficial effects of the BWL in synchronizing circadian rhythms. Aim 4 - Exploratory: Explore potential moderators of the intervention including seasonality, chronobiology, personality, and social factors.

Adjunctive Allogeneic Mesenchymal Stem Cells for Treatment-resistant Bipolar Depression
Treatment-resistant Bipolar DepressionThe overall objective of the investigators is to assess the therapeutic efficacy and tolerability of Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs) isolated from hematogenous bone marrow for treatment of treatment-resistant bipolar depression patient (TRBD).