Bipolar Disorder I or II

This is a single site trial in 30 patients with schizophrenia, schizoaffective, or bipolar I/II/NOS disorder in which all participants will receive eight weeks of olanzapine and samidorphan (Olz/Sam) plus four weeks of aerobic exercise.

Bipolar disorder often runs in families, but early symptoms in youth can go unrecognized for years. This project evaluates a structured, family-centered approach to informed screening for youth ages 7-21 who have a biological parent with bipolar disorder. The main questions addressed by this project are: Whether a co-designed video decision aid improves caregiver understanding of bipolar disorder genetic risk and supports informed decisions about youth screening. Whether remote mental health screening tools are feasible and acceptable for youth with familial risk for bipolar disorder. Whether screening results can be used to identify early risk patterns and inform tailored follow-up recommendations. Participants may be involved in one or more study activities, including co-design of educational decision-aid content, feedback on decision-aid prototypes, beta testing of the decision aid, and remote youth mental health screening. The study does not assign treatment and does not change existing clinical care or clinic routines.

The goal of this clinical trial is to learn if intravenous (IV) ketamine with Dialectical Behavioural Therapy (DBT) reduces suicidal ideation in individuals with suicidality who have been diagnosed with Borderline Personality Disorder and either Major Depressive Disorder or Bipolar Disorder. The main question it aims to answer is: Does IV ketamine and DBT produce more rapid and robust improvements in suicidal ideation (SI) severity between baseline and Day 35 compared to IV midazolam and DBT, as measured by changes in the Modified Scale for Suicidal Ideation (MSSI) scores ? Researchers will compare six IV ketamine infusions and DBT to an active placebo (a look-alike substance that mimics some of ketamine's effects and not others) and DBT to see if IV ketamine with DBT is more effective at reducing SI severity. Participants will: * Complete six infusions of either IV ketamine or IV midazolam * Take part in 6 months of DBT (includes both weekly one-on-one sessions, and group sessions, starting week 5 of the trial) * Visit the hospital for scheduled in-person visits * Join a call or videocall for scheduled remote visits * Complete a variety of different mood, cognitive and behavioral assessments

The present study is an open trial of ketogenic diets for adolescents and young adults (ages 12-21 yrs) in the depressive or mixed phases of bipolar disorder (BD). The investigators aim to determine whether combining standard of care pharmacological treatment for bipolar spectrum disorders with a 16-week ketogenic diet is well-tolerated and associated with improvements in depression, inflammatory and metabolic indicators, and executive functioning over the study period. The experimental treatment in this study is a 16-week full ketogenic diet. Four study sites (UCLA, U Cincinnati, U Colorado and U Pittsburgh) will recruit 80 total youth (20 each) from bipolar specialty clinics. All youth eligible for the ketogenic therapy will be provided with the ketogenic diet and standard of care pharmacological treatment. During the diet therapy youth will be seen by a study child/adolescent psychiatrist at least once a month (and more frequently when needed), with the psychiatrist recommending and providing side effects monitoring and pharmacotherapy as clinically indicated. The youth and caregivers will also meet with an expert dietitian who will coach all youth on maintaining the ketogenic diet (low carbs, high fats, medium protein) and making sure the child is tolerating the diet and getting enough liquid and nutrients, following the practice guidelines of the International Ketogenic Diet Study Group for treating youth. All youth and involved caregivers will also be provided will at least one motivational enhancement session to support them in goal setting and completion of the study elements. Throughout the study the investigators will assess metabolic (e.g., blood ketones, HOMA-IR) and inflammatory indicators (e.g., C-reactive protein), both for safety reasons and to assess correlates of symptomatic change. Independent evaluators will assess youth every month regarding their symptoms (depression, mania, anxiety, psychosis), psychosocial functioning, and quality of life. The investigators anticipate that the pilot will transpire over 24 months and be an important step toward establishing feasibility and acceptability of ketogenic therapy for this population, not only in terms of diet administration and compliance but also for obtaining symptomatic, metabolic and inflammatory measurements.

The goal of this neuroimaging study is to investigate how emotional states fluctuate in people with bipolar disorder (BD) compared to healthy controls, and to understand the neural mechanisms driving mood instability. The main questions it aims to answer are: * Can emotional states be decoded from fMRI brain activity using machine learning? * Do individuals with BD show more unstable emotional state trajectories (e.g., high metastability, low fractal scaling) than healthy controls? * Does amplifying positive emotions stabilize brain and emotional dynamics in BD? Researchers will compare individuals with bipolar disorder (BD-I or BD-II, currently depressed or mixed state) to healthy controls without psychiatric history to see whether the BD group shows greater fluctuations in emotional brain activity and whether positive emotion regulation strategies normalize this instability. Participants will: * Complete self-report questionnaires on mood, emotion regulation, anxiety, and daily functioning. * Recall and provide short descriptions of personal positive and negative memories to be used in the MRI task. * Undergo fMRI scanning, including: * Resting-state scans * A Think and Regulate Affective States Task (TReAT) where they recall autobiographical memories, rate emotions, and practice amplifying positive mood. * Structural and diffusion MRI for brain mapping. * Receive physiological monitoring (heart rate, respiration) during scanning. * Complete post-scan surveys on emotional state and task experience. This research will help clarify how the brain supports or disrupts emotional regulation in bipolar disorder and may inform the development of personalized, neurobiologically informed treatments for mood instability.

This is a single site trial in 30 patients with schizophrenia, schizoaffective, or bipolar I/II/NOS disorder in which all participants will receive eight weeks of olanzapine and samidorphan (Olz/Sam) plus four weeks of aerobic exercise.

The aim of this study is to determine whether it is feasible to deliver a 9-session compassionate-focused therapy for older people with bipolar disorder. Participants will be asked to complete baseline measures and at post-intervention follow-up (12 weeks and 24 weeks) to understand any potential clinical benefits of the therapy.

The main goal of this study is to determine if brain lithium-concentrations predict clinical lithium treatment-response. Secondary, to study correlations between intracerebral distribution-patterns of lithium with clinical treatment outcome. Brain lithium concentrations will be measured using ultra-high field (7 Tesla) lithium magnetic resonance (MR) imaging, which has recently been introduced. Determining lithium-concentrations in the brain has been difficult so far due to lithium's relatively low concentration (compared to protons, which are targeted in conventional MRI). 7T lithium MR imaging has the potential to produce much more detailed MR images compared with previous studies, for the first time. The BLISS study is expected to yield new insights, helping to better understand why clinical lithium response varies between individuals.