Bipolar Depression

The purpose of this research is to understand how changes in RNA editing relate to treatment response in unipolar and bipolar depression.

X-CEED is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of azetukalner in adult participants diagnosed with bipolar I or II disorder who are currently in a depressive episode (bipolar depression).

The aim of this study was to explore the efficacy and safety of temporal interference stimulation to improve bipolar depression, as well as to explore the corresponding neuroimaging mechanisms using magnetic resonance and electroencephalogram to provide novel intervention protocols and objective indicators of efficacy prediction for depressive episodes in bipolar disorder.

Bipolar disorders (BD) are a group of complex disorders that impact mood, behaviour and cognition and are known to cause significant suffering and impairment. Circadian rhythm (your internal day/night "clock") disruption, which can involve changes in sleep-wake cycles, frequently occurs in BD. Both depression and mania are accompanied by circadian disruption. These disruptions are hypothesized to lead to mood worsening, metabolic dysfunction and inflammation. If circadian dysfunction plays a significant role in the symptoms and trajectory of BD, then treatment approaches that target these functions may lead to better outcomes. One such approach is dietary interventions. Time restricted eating (TRE) is a dietary tool that restricts the eating to an 8-12 hour window, without changing diet quality or caloric intake. Studies involving time restricted eating have been done in other conditions with promising results. There have been no studies done for mood disorders in general or bipolar disorder specifically. In this proposal, the investigators will assess two dietary interventions (TRE and nutritional counselling) to examine how TRE may represent a safe and viable adjunct to traditional treatments. The investigators aim to compare TRE with nutritional counselling, while all participants continue to receive usual care. Participants will receive support from a registered dietician and will be instructed on dietary habits. Half of participants will receive nutritional counselling and half will be asked to do TRE. Those in the TRE group will be asked to select a 10-hour window to consume all food and non-water beverages for the 8-week period. Participants will be asked to complete a screening visit to determine eligibility, and then will complete questionnaires at baseline, week 4 and week 8 examining symptoms of their illness and cognition. Participants will also provide a blood sample at baseline and week 8 for standard biochemistry tests, pregnancy testing (if applicable), and to examine inflammatory markers. Participants will also wear an actigraphy watch which provides wireless continuous monitoring of movements and ambient light. The primary outcome is feasibility and acceptability (do people agree to participate, complete the study, and follow the intervention; what do they think of the intervention). Secondary outcomes include changes in depression, anxiety, sleep, and cognition. Exploratory outcomes include inflammatory markers and circadian disruption.

The purpose of this trial is to determine if intermittent theta-burst stimulation (iTBS) can reduce the symptoms of depression in treatment-resistant bipolar disorder. To do this, some of the participants in this study will receive treatment with active iTBS stimulation, while others will receive sham iTBS stimulation. Participants will come for 30 days of either active iTBS or sham iTBS, with a 6-week follow-up period. Symptoms of depression (for determining treatment efficacy) and mania (for determining treatment safety) will be assessed using the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Young Mania Rating Scale (YMRS) every five treatments during the treatment course, and at 1 week and 6 week after treatment completion.

Bipolar disorder is a long-term mental health condition that causes mood changes, with depressive episodes being the most frequent and disabling. Many people do not fully recover with current treatments, showing the need for new therapeutic options. Recent research shows that insulin resistance (IR), a condition in which the body does not respond well to insulin, is common in people with bipolar disorder. It is linked to more severe mood symptoms, poorer treatment response, and higher risk of heart disease. IR may raise inflammation and affect how the brain uses energy, which can influence mood regulation. Empagliflozin is a medicine approved for type 2 diabetes. In addition to its metabolic and heart benefits, studies suggest that it may also protect the brain and reduce inflammation, possibly helping to improve mood. This open-label, proof-of-concept clinical trial will test how well empagliflozin works and how safe it is as an add-on treatment for people with bipolar depression and insulin resistance. A total of 20 adults with bipolar disorder type I or II, currently in a depressive episode, will take part in the study over a 12-week period. The main goal is to see whether empagliflozin can lower depressive symptoms, measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). Other measures include changes in insulin resistance and incidence of adverse events. The study aims to explore whether improving insulin resistance can help both mood and metabolic health in people with bipolar disorder, guiding future clinical research.

The purpose of this study is to examine the effects of interventional/procedural therapies for treatment-resistant depression (TRD) and Obsessive-Compulsive Disorder (OCD). These treatments include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), racemic ketamine infusion and intranasal esketamine insufflation. The investigators will obtain various indicators, or biomarkers, of a depressed individuals' state before, during, and/or after these treatments. Such biomarkers include neurobehavioral testing, neuroimaging, electroencephalography, cognitive testing, vocal recordings, epi/genetic testing, and autonomic nervous system measures (i.e. "fight-or-flight" response). The results obtained from this study may provide novel antidepressant treatment response biomarkers, with the future goal of targeting a given treatment to an individual patient ("personalized medicine").

Individuals with Bipolar Disorder (BD) have twice the risk of being affected by metabolic comorbidities and a 1.8-fold increased risk of mortality from cardiovascular diseases when compared to the general population. These factors are fundamental in the 14-year reduction in the life expectancy of people with TB reported in recent meta-analyses. This occurs mainly due to the increased inflammation associated with the disease, the adverse effects of pharmacological treatments and unhealthy lifestyle habits that are more common in people diagnosed with BD. Nutrition has been studied as an adjunctive treatment in other psychiatric disorders, but there is a lack of studies about the role of nutrition in TB. Considering that diet can impact metabolic health, this randomized controlled study aims to evaluate the effect of a nutritional intervention on cardiovascular risk in patients with TB. The intervention is based on the dietary pattern recommended in the Dietary Guidelines for the Brazilian Population and will be applied by a registered dietitian. According to the literature, the sample size will be 72 individuals with TB (36 in the control group with usual treatment + 36 in the intervention group added to the usual treatment). The intervention will be carried out in 7 individual sessions and 8 group sessions with specific themes. The primary aim of this protocol will be an intervention to contribute to cardiovascular health - verified by serum markers, anthropometric measurements and the Framingham Cardiovascular Risk Score (algorithm used to estimate an individual's 10-year cardiovascular risk). The secondary stages will be the adherence of the intervention and the impact on the quality of life of the participants. The possible positive results of this nutritional intervention can open new clinical perspectives. Meaning that might show that better food choices can protect the cardiovascular health of individuals with TB, leading to a reduction in morbidity and mortality associated with the disease.

The aim of this study is to evaluate the feasibility and efficacy of deep transcranial magnetic stimulation (dTMS) as an add-on treatment for bipolar depression. Meanwhile, we aim to evaluate the effect of dTMS on cognitive function of bipolar depressive patients. We hypothesize dTMS would improve depressive symptoms and cognitive function in bipolar disorder.

The purpose of this study is to assess the clinical correlates of therapeutic precision ketosis in bipolar depression and to evaluate the cardiometabolic correlates associated with therapeutic precision ketosis in bipolar depression.

This study is only enrolling at Baylor College of Medicine. The other research locations listed serve to support data analysis only. This research study is to investigate the use of technology called Deep Brain Stimulation (DBS) to potentially improve Treatment-Resistant Bipolar Depression (TRBD) symptoms in patients with severe cases. DBS involves the surgical implantation of leads and electrodes into specific areas of the brain, which are thought to influence the disease. A pack implanted in the chest, called the neurotransmitter, keeps the electrical current coursing to the brain through a wire that connects the neurotransmitter and electrodes. It is believed DBS may restore balance to dysfunctional brain circuitry implicated in TRBD. The goal of this study is to enhance current approaches to DBS targeting in the brain and to use a novel approach to find a better and more reliable system for TRBD treatment. Its important for participants to understand that this is an investigational study where there could be a lack of effectiveness in improving TRBD symptoms. There may be no directly benefit from taking part in this study. This study is expected to last 20 months and involves 3 main steps. 1. Medical, psychiatric, and cognitive evaluations. 2. Implantation of a brain stimulation system. 3. Follow up after implantation of device, including programming, recording, and psychiatric testing. There are risks and benefits to this study which need to be considered when deciding to participate or not. Some of the risks are from surgery, the DBS device and programming, the tests involved, and potential loss of confidentiality, as well as other unknown risks. Some of the more serious risks involved in this study and the percentage that they occur: 1. Bleeding inside the Brain (1 to 2 percent). 2. Infection from the procedures (3 percent) 3. Seizure caused from the procedures (1.2 percent) However, the benefit of this study is that it may help relieve or decrease TRBD symptoms. This form of treatment has shown to reduce symptom severity in other cases. This could potentially improve quality of life and activities in daily routines. There is also a potential benefit to society in that the data the investigators will obtain from this study may help increase the understanding of the mechanisms underlying TRBD symptoms, as well as enhanced Deep Brain Stimulation techniques. Study participation is expected to last 20 months from the time the DBS device is activated and should include approximately 23 visits. These visits also include 8 separate, 24 hour stays at the Menninger NeuroBehvaioral Monitoring Unit (NBU). These 24-hour sessions will occur at multiple points throughout the study (1 week prior to surgery, the week preceding device activation, the week following activation, then after 2 weeks, 4 weeks, 6 months, 9 months, and 12 months). Participants will need to stay locally for the week of the NBU stay (typically Monday through Friday). Study visits will include clinician administered assessments and questionnaires, subject reported assessments, neuropsychological testing, and mobile behavioral assessments which will occur around 23 visits over the course of 20 months.

Schizophrenia, bipolar and major depressive disorders collectively affect over 10 million people across the EU and are associated with annual healthcare and societal costs in excess of 100 billion Euros. When diagnosed with one of these disorders, patients are prescribed psychotropic medication such as antidepressants, mood stabilisers or antipsychotics. It is unknown whether this first-line treatment will be successful. After this first-line treatment fails, usually a second-line treatment is initiated, and when this is not successful either a third-line treatment is initiated. Third-line treatments are quite successful, especially when compared to second-line treatments. The research question is whether the third-line treatments (early-intensified treatments) when used earlier in the disease course for schizophrenia, bipolar and major depressive disorders. If this is indeed the case, this could lead to the prevention of unnecessary trials of ineffective treatments and adaptations of worldwide guidelines as well as a reduction of healthcare and societal costs.

This randomized, double-blind, sham-controlled clinical trial aims to evaluate the efficacy and underlying biological mechanisms of HD-tDCS targeting the primary somatosensory cortex in adolescents with bipolar depression. Participants will be randomly assigned to receive either active HD-tDCS or sham stimulation, in addition to routine clinical care. Biological data, including neuroimaging, blood biomarkers, voice and facial features, Photoplethysmography (PPG), Electroencephalography (EEG), and behavioral data, will be collected to explore potential predictors of treatment response.

Bipolar disorders affect approximately 4.5 million people across the European Union (EU) and are associated with high annual healthcare and societal costs. Bipolar disorder I and II represent disorders that cause extreme fluctuation in a person's mood, energy, and ability to function, in which symptoms of (hypo)mania and depression alternate. The depressive episodes of bipolar disorders are often referred to as bipolar depression (BD). In other words: it is a phase/state of the disorder. For many patients with BD, the depressive polarity is often more pervasive and more debilitating than manic states, with estimates that depressed mood accounts for up to two-thirds of the time spent unwell, even with treatment. The burden of not received an effective treatment for BD is high: more severe psychopathology, higher rates of unemployment, more hospitalisations, lower quality of life, lower cognitive functioning, risk of suicide, comorbidities and poorer social and occupational functioning and thus more carer burden. For BD, the treatment guidelines are very heterogeneous, amongst other reasons because the disease is heterogeneous and treatments should be tailored to the patients. There is no clear treatment algorithm and it cannot yet be predicted which treatment will be effective. Especially the place of adjunctive antidepressants is under debate. Usually, for psychiatric disorders (including bipolar disorder), a patient is considered to be treatment-resistant is two medicinal treatments have been tried (in sufficient duration and dosage) without sufficient success. For BD, there is no consensus on when to consider a patient as treatment-resistant, but the most common definition is after one prior treatment failure. This raises the research question whether adjunctive antidepressants to treat BD should be introduced earlier in the treatment. Additionally, The INTENSIFY trial is part of the larger Horizon 2021 project, with the central goal of paving the way for a shift towards a treatment decision-making process tailored for the individual at risk for treatment resistance. To that end, we aim to establish evidence-based criteria to make decisions of early intense treatment in individuals at risk for treatment resistance across the major psychiatric disorders of schizophrenia, bipolar disorder and major depression.

The goal of this clinical trial is to evaluate the safety and initial effectiveness of MR-guided focused ultrasound (MRgFUS) bilateral capsulotomy in patients with treatment-resistant bipolar depression (TRBD).

This is a multicenter, randomized, double-blind, placebo-controlled study in pediatric patients who are experiencing major depressive episodes (MDEs) associated with a primary diagnosis of bipolar I or bipolar II disorder as confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5).

This is a 2x2, within-subjects, cross-over trial to test the anti-depressant effects of acute exercise in 20 participants with bipolar depression. Participants will complete four experimental sessions, two with an exercise challenge and two with a resting control condition in a counterbalanced order. Participants will receive either 800mg of ibuprofen or placebo before exercise or rest in order to test whether blocking the inflammatory response to exercise interferes with the neural and psychological effects of exercise.

Bipolar disorder (BD) affects between 1-3% of the world's population. People with BD experience episodes of mania or hypomania and in most cases, they experience periods of depression which can cause difficulties in daily life. Psychological therapies for people experiencing depression without mania or hypomania are widely available, but there is little research into how effective these therapies are for people with BD. Behavioral activation therapy (BA) is based on behavioral theory and has been proven to be an effective treatment for unipolar depression. It helps people re-establish healthier activity patterns and sleep regulation, especially in BD for mood stabilization. BA is theoretically and clinically well matched to the treatment of bipolar depression, but there is still very little research into offering BA to people with BD. The first aim of the current research is to implement BA for people with depression in Bipolar Disorder and study if it is feasible for this patient group. The second aim is to do a pilot study on the effectiveness of the treatment for this patient group. The research will be implemented with people seeking treatment at the specialized service for bipolar disorder at Landspítali University Hospital in Iceland. The participants will receive treatment as usual and the BA will be adjunctive. At least ten people, that are currently experiencing Bipolar Depression and are willing to take part, will receive up to 20 individual therapy sessions of BA that have been adapted for Bipolar Depression (BA-BD), and will complete regular questionnaires and interviews. The study will be a replication study to validate the previous study's findings by Kim, W. et al., 2022 in another setting.

An explorative, open label, single armed, flexible dose, single center, phase IIa study of 8 weeks, initiated in subjects with bipolar depression. The study will consist of 9 visits and 1 safety visit. Subjects with a primary diagnosis of bipolar disorder (type 1 or 2) currently in an acute depressive phase (i.e. bipolar depression) and being on stable medication with at least one mood stabilizer.

This study is an open-label, single-arm, proof-of-concept study, wherein treatment resistant bipolar depression (TRBD) participants will receive one 25 mg dose of oral psilocybin accompanied by preparatory, monitoring, and integration psychotherapy sessions (psilocybin-assisted psychotherapy, or PAP). Using fMRI (functional magnetic resonance imaging), the findings of this study will provide data on the neurobiological mechanism of psilocybin in TRBD. The primary objective is to understand the dynamic role of amygdala activity by evaluating the neurobiological effects of a single psychedelic dose (25 mg) of oral psilocybin in individuals with a moderate to severe major depressive episode and a primary diagnosis of Bipolar II Disorder, with 2 or more failed treatment trials (i.e., treatment resistant bipolar depression \[TRBD\]). Neurobiological effects will be determined by evaluating the association between post-treatment right amygdala activity during the facial affect task (determined by fMRI one day after the psilocybin dose) and antidepressant effects (determined by changes in the Montgomery-Åsberg Depression Rating Scale \[MADRS\] scores over time, during the one-week period post-psilocybin dose). This is a single-arm, open-label clinical trial wherein all participants will receive the same study intervention. Hypothesis: Increased right amygdala activity on fMRI with emotional stimuli one day after psilocybin treatment will be associated with greater antidepressant effects in the one-week period post-treatment in individuals with TRBD.

Bipolar disorder (BD) is a frequent and lifelong recurrent mood disorder with treatment-resistant depressive episodes. Importantly, depressive symptoms and cognitive decline are major determinants of functionality and quality of life in this clinical population. There is robust evidence that individuals with BD have neurocognitive deficits (especially in memory and executive functioning domains) compared to the healthy population. These deficits are present in all mood states and can greatly affect patients' functional capacity, often more so than mood symptoms themselves. Many pharmacological treatments for BD adversely affect cognition, and those that are beneficial can be difficult to use. There is thus a pressing need to identify a safe, easy-to-use medication that can target both cognitive deficits and depressive symptoms in BD. It is expected that Brexpiprazole adjunctive treatment will be efficacious in treating BD type I and type II depression by improving mood symptoms, as well as cognitive capacity and global functioning, and that such changes will be accompanied by concurrent alterations in associated brain structures.

Major Depressive Disorder (MDD) is a serious mental illness and public health problem that poses threat to both physical and mental health. According to statistics from WHO, it is estimated that more than 350 million people worldwide suffer from depression, with a prevalence rate of 2.1% in China, which is approximately 30 million people. At present, due to the lack of neurobiological markers for screening and diagnosing depression, the identification and diagnosis of MDD are based on the judgment of professional doctors, and the treatment mostly relies on clinical symptoms. In terms of treatment, medication remains the main stream for MDD. Although current methods have certain therapeutic effects, patients still suffer from various side effects and poor cognitive function.In current clinical practice, relying purely on symptomatic diagnosis and treatment is difficult to meet the needs of clinical practice, so there is an urgent need to search for neurobiological markers in depression and develop targeted non-invasive intervention technologies. This study aims to combine advanced brain imaging technology, digital twin-brain models, multi-source information decoding technology, integrated detection and intervention technology. The target is to create two new types of non-invasive BCI systems that can regulate emotions. One is a intervention BCI system for MDD that is suitable for hospital settings with the purpose of precise physical stimulation, and the other one is an ecological BCI system that regulate emotions and intervene with depression which is suitable for both hospital settings and future family environments. This study will collect a comprehensive collection of physiological and biochemical indicators from patients with depression and from healthy control groups, as well as multimodal information such as head surface electroencephalography, MRI, and eye movements under different brain states, to personalize the available BCI information of depression related brain regions, circuits, and networks. The study also tries to explore emotional-interactive games that can intervene with depression and build a game data base that is dedicated to MDD. Other goals include designing and establishing two new types of emotional regulation systems, which are precise external physical stimulation intervention and ecological intervention, constructing a BCI regulation system, and conducting application verification to evaluate the regulation effect.