Psychosis

The purpose of this trial is: * To investigate whether the response to clozapine treatment can be enhanced by adding cannabidiol (CBD), compared to placebo, in treatment resistant psychosis patients. * To confirm the safety of CBD in people with psychosis. The trial is a randomised, double-blind, placebo-controlled, multi-centre, international, clinical trial. Individuals with a diagnosis of treatment resistant psychosis in their illness who have had a suboptimal or no response to clozapine treatment will be recruited. These patients are randomised to treatment with oral CBD 500mg twice daily, or a matching placebo for 12 weeks, in addition to clozapine, which is standard care treatment for this population. By using a battery of clinical outcome assessments, the trial will assess several optional biomarkers to predict clinical outcomes and response to treatment with CBD. Biomarkers are being assessed as an exploratory outcome measure. Participants will be invited to provide additional blood samples, stool samples, and complete neuroimaging assessments.

The purpose of this study is: * To investigate whether the response to antipsychotic treatment can be enhanced by adding cannabidiol (CBD) to the existing treatment, compared to placebo, in participants with a first episode of psychosis, who have had a suboptimal or no response to their first antipsychotic treatment. * To confirm the safety of CBD in people with psychosis. The study is a randomized, double-blind, placebo-controlled, multi-centre, clinical trial. Individuals with a diagnosis of first-episode psychosis, who have had a suboptimal or no response to their first antipsychotic treatment will be recruited. These participants are randomised to treatment with CBD oral solution 500mg twice daily, or a matching placebo for 6 weeks, as an adjunct to their existing antipsychotic treatment. By using a battery of clinical outcome assessments, the trial will also assess several biomarkers to determine if they can be used to predict clinical outcomes and response to treatment with CBD. Biomarkers are being assessed as an exploratory outcome measure. Participants will be invited to provide blood and stool samples, and may be asked to complete neuroimaging assessments at certain eligible sites.

People with psychotic disorders are excluded from most suicide-focused clinical trials despite incredibly high rates of completed suicide, and interventions that have been tested for this population have shown limited impact on suicide. Emotion dysregulation is a significant suicidogenic factor that is understudied in people with psychotic disorders. The investigators propose to implement and evaluate an intervention targeting emotion dysregulation in people with psychotic disorders while employing rigorous statistical modeling and measurement techniques including Ecological Momentary Assessment, which will support future advanced research on suicide and suicide prevention for this high-risk group.

People with bipolar disorder (BD) are at high risk of relapse following hospital discharge, partly due to a lack of BD-specific expertise and resources within community services required for comprehensive treatment. Although clinical guidelines recommend combining medication and psychosocial support, and research shows that early intervention is associated with improved outcomes, no structured care programs currently exist for individuals in the early stages of BD, contributing to chronic illness progression and preventable hospitalizations. This open-label pilot trial will assess the feasibility, acceptability, and preliminary effectiveness of a structured care pathway to support the transition from hospital to community care. The intervention includes group-based psychoeducation, individual peer support, and personalized support for community healthcare providers to improve illness insight, treatment adherence, and symptom management.

The aim of this trial is to evaluate the feasibility and preliminary efficacy of using passive smartphone sensors to detect moments of heightened negative mood and inform the timing of brief mental health interventions, such as mindfulness exercises and psychoeducation, in adults with early psychosis.

This observational study will examine behavioral and electroencephalography measures related to state representation in individuals with early psychosis and healthy control participants. Participants will complete clinical interviews, self-report measures, cognitive assessments, computerized behavioral tasks, and EEG assessments. The study will evaluate performance and computed parameters from the Translational Orientation Pattern Expectancy task and Translational Bandit Task, along with EEG variables related to cognitive control, reward processing, and neural synchrony. The study aims to better understand heterogeneity in early psychosis and identify neurocognitive and neurophysiologic markers that may inform future precision psychiatry approaches.

Some people hear voices or sounds that other people cannot hear; these are called auditory hallucinations. The study aims to understand what is happening in the brain when this occurs and will use brain scans to learn more. Greater understanding should help develop better treatments in the future.

Psychosis is a serious mental health condition that can affect how a person thinks, feels, and functions in daily life, often making it harder to maintain relationships, continue education, or work. Even with standard treatment, many people continue to experience emotional distress, depression, anxiety, and difficulty coping with strong emotions. These challenges can worsen recovery, increase the risk of substance use and suicidal behaviour, and place a significant burden on individuals, families, and the healthcare system. Dialectical Behaviour Therapy (DBT) is a skills-based psychological treatment that helps people manage emotions, tolerate distress, and improve relationships. Although DBT has been effective in other mental health conditions, it has not been well studied in people with first-episode psychosis. This study will evaluate an 8-week group DBT skills training adapted for individuals with first-episode psychosis. The study aims to assess whether the program is acceptable and feasible to deliver, and whether it may improve emotion regulation, mood, resilience, and functioning. Findings will inform whether a larger clinical trial of this intervention should be conducted.

Psychotic disorders affect approximately 4% of Canadians and have a significant impact on individuals' well-being, their families and social networks, and healthcare systems. The development of psychosis is explained by a complex interplay of genetic and environmental factors, including the use of psychoactive substances. Frequent cannabis use can contribute to the development of psychotic disorders. The prevalence of cannabis use disorder (CUD) in individuals with a first-episode psychosis (FEP) followed in Early Intervention Services (EIS) is 42-53%, well above that of the general population (\~3%). Cannabis use in individuals with psychosis is associated with increased symptom severity, higher rates of relapse and hospitalization, and poor psychosocial functioning. Standardized mobile app-based interventions offer a scalable and accessible solution. Our team developed and piloted CHAMPS (harm reduction) and iCanChange (use reduction/cessation) with favourable results: retention 82% (CHAMPS) and 84-86% (iCC), high satisfaction, and preliminary efficacy signals. The two pilot studies were targeting feasibility, this study is studying efficacy of the two app-based interventions (CHAMPS and iCanChange).

The investigators are conducting a pilot feasibility and preliminary efficacy trial of a digital intervention for serious mental illness in West Africa. Participants will be recruited from a large psychiatric hospital in Ghana and will be asked to use a digital intervention titled G-FOCUS.

The goal of this clinical trial is to learn about cognition in psychotic disorders (schizophrenia, bipolar disorder, and schizoaffective disorder). The main question it aims to answer is: Can we use magnetic stimulation to change processing speed (how quickly people can solve challenging tasks). Participants will be asked to perform cognitive tasks (problem-solving) and undergo brain scans before and after transcranial magnetic stimulation (TMS). TMS is a way to non-invasively change brain activity. Forms of TMS are FDA-approved to treat depression and obsessive compulsive disorder. In this study, we will use a different form of TMS to temporarily change brain activity to observe how that changes speed in problem-solving.

This is a randomized, controlled clinical trial to assess the effects of the ketogenic diet in combination with treatment as usual on brain energy metabolism and psychiatric symptoms in individuals with first episode bipolar disorder and schizoaffective disorder.

Young people at clinical high risk for psychosis are more likely to experience suicide thoughts than the general population, but there are few suicide prevention programs designed specifically for them. This study will develop and evaluate a recovery-oriented suicide prevention group program for young people at clinical high risk for psychosis. The program will be led by a clinician and a peer with lived experience. It will help participants identify reasons for living, build hope, set meaningful recovery goals, strengthen social connections, and learn strategies to better remember and use suicide prevention strategies developed during the program. Caregivers will also be invited to participate in a session to learn ways to support their young person. The study will first gather feedback from participants, caregivers, clinicians, and community advisors to refine the program. Researchers will then compare the program plus standard care with standard care alone to determine whether it improves personal recovery and increases participants' ability to remember and use suicide prevention strategies. Researchers will also collect feedback from participants and program staff to better understand how the program can be integrated into early psychosis services.

This randomized, double-blind, sham-controlled trial compares three brain stimulation approaches-accelerated intermittent theta burst stimulation (aITBS), high-frequency repetitive transcranial magnetic stimulation (HF-rTMS), and sham stimulation-for treating cognitive deficits in treatment-resistant schizophrenia. Ninety patients receiving clozapine will be randomized 1:1:1 to receive 20 sessions over 4 weeks targeting the dorsolateral prefrontal cortex. The primary outcome is change in cognitive function measured by B-CATS score at 2, 4, and 12 weeks. Secondary outcomes include social cognition, symptom severity, brain metabolism (FDG-PET), and inflammatory biomarkers.

The study examines (1) the effects of active anodal (facilitatory) tDCS and yoga combined intervention on cognitive function, clinical symptoms, and quality of life domains (social function and physical wellbeing) in psychosis, and (2) the neurophysiological mechanisms underlying the effects induced by the combined intervention.

Background Psychosis is a mental health condition that affects around 3 in 100 people in their lifetime. Most treatments for psychosis target a brain chemical called dopamine but they don't work for everyone and don't address many of the symptoms. People with psychosis and people at risk of developing psychosis show differences in a part of the brain called the hippocampus, such as smaller size and increased activity. This hyperactivity may be associated with cognitive difficulties (thinking and memory). The basis of this hippocampal hyperactivity is thought to be a deficit in excitation and inhibition of brain cells. Excitation causes brain cells to send signals more frequently, and inhibition causes cells to send signals less frequently. A balance between these signals is important for the brain, including the hippocampus, to function properly. Approach Levetiracetam is a medication that is widely used to treat epilepsy and which helps balance excitation-inhibition in the brain. We will use brain imaging, using Magnetic Resonance Imaging (MRI), to test if levetiracetam can help reduce hippocampal hyperactivity, alter connectivity and change levels of brain chemicals in people who are at risk of developing psychosis. Participants (18-40 years), identified as at risk of psychosis through the Outreach and Support in South London (OASIS) teams, will attend an initial visit at the Institute of Psychiatry, Psychology \& Neuroscience. This will involve questions about experiences and feelings, assessment of thinking and memory, and a blood test. They will then attend two scanning visits at the Centre for Neuroimaging Sciences, during which they will take capsules of either levetiracetam or placebo (in a randomised order) before having a 60 mins MRI scan. The MRI scan will look at blood flow to the hippocampus, resting activity, activity during a cognitive task and levels of brain chemicals. A case-control sample of 33 healthy individuals aged 18-40 will be recruited from Greater London. We will recruit a healthy control (HC) sample to establish the presence of hippocampal dysfunction in our CHR-P group by comparing the MRI data for CHR-P under the placebo condition with that of the HC sample. The HC individuals will attend the screening visit and one scanning visit. They will not receive any medication. Funded by the Wellcome Trust and conducted by King's College London researchers, the study spans 2-3 months per participant. Impact Our study will provide important evidence about how levetiracetam affects brain function, and how this relates to cognition. This knowledge may lead to innovative approaches for understanding and treating psychosis early.

This clinical trial will evaluate the effectiveness and cost-effectiveness of a link work intervention for supporting people with severe mental health difficulties to attend a routine dental appointment. There are two main outcomes, namely: i) attendance at a routine dental appointment; and ii) oral health quality of life. The main predictions are that: 1. The link work intervention plus treatment as usual will lead to greater likelihood of attendance at a routine dental appointment, compared with treatment as usual alone. 2. The link work intervention plus treatment as usual will lead to better oral health quality of life, compared with treatment as usual alone. 3. The link work intervention plus treatment as usual will be cost-effective compared with treatment as usual alone.

This is a clinical trial study that aims to evaluate the specificity of the relationship between reduced sensitivity to social reward and social anhedonia at both behavioral and neural levels. Individuals who recently experienced their first-episode psychosis will be recruited. Participants will be randomized 1:1 to motivational interviewing or a time- and format-matched control probe. At pre- and post-probe, participants will perform two social reward learning tasks in the scanner. With this design feature, we will examine the relationship between sensitivity to social reward and reduced subjective experience of social pleasure at both the behavioral and neural levels.

The goal of this clinical trial is to learn more about decision making in psychosis spectrum disorders, like schizophrenia. Participants will be people who have had symptoms of a psychosis spectrum disorder start within the last five years. The investigators will study how two study agents change decision making in people with psychosis, by asking participants to complete some brain games on the computer before and after taking the study agents. The investigators hope to improve our understanding of psychosis to help people in the future. The main research questions are: * Does a single dose of modafinil change how people with psychosis play the brain games? * Does a single dose of d-serine change how people with psychosis play the brain games? * Does a single dose of modafinil change brain activity? * Does a single dose of d-serine change brain activity? Participants will: * Complete an interview and self-report questionnaires. * Complete safety screening activities, like a blood draw, a urine drug test, and an alcohol breathalyzer test. * Complete functional Magnetic Resonance Imaging (fMRI) scans. fMRI uses magnets to take pictures of the brain. There will be six scanning appointments in the study, with two scans each. Appointments will be about a month apart. * Take a single dose of a study agent during each scanning appointment. The study agent will be taken after the first fMRI. There are three study agents in total: modafinil, d-serine, and a placebo. Each participant will take each study agent twice during the study. * Play brain games on a computer that measure decision making, thinking, and problem solving skills

This study examines whether an early-detection program for psychosis can shorten the time patients remain untreated after the first appearance of psychotic symptoms, and whether such a reduction improves later functioning for people with first-episode schizophrenia. Psychosis involves symptoms such as hallucinations and delusions. When these symptoms are recognized and treatment begins, most patients improve. However, many individuals live with psychotic symptoms for months-or even longer-before receiving care. This period is known as the duration of untreated psychosis (DUP). A long DUP has repeatedly been linked to poorer long-term outcomes, but it is still unclear whether DUP itself causes worse outcomes or simply reflects different illness courses. In Denmark, Region Zealand has implemented a large-scale early-detection effort. This includes public awareness campaigns and a specialized team that identifies people with emerging psychosis and helps them start treatment quickly. The Capital Region of Denmark provides usual care without these additional initiatives. This situation makes it possible to compare two regional systems that differ in their approach to early detection but provide the same specialized treatment once patients enter care. The study follows a quasi-experimental design, recruiting adults (18+) who receive a first diagnosis of a schizophrenia-spectrum disorder within the OPUS early-intervention programs in the two regions. No interventions are assigned by the research team; participants receive standard clinical care. Researchers conduct interviews to establish how long psychotic symptoms were present before treatment began and to assess functioning and symptoms over a two-year follow-up period. Functioning, symptoms, cognition, and treatment factors will be examined at baseline and at follow-ups. The study addresses three questions: Whether early-detection efforts in Region Zealand reduce the duration of untreated psychosis compared with usual detection. Whether a shorter duration of untreated psychosis leads to better functional and clinical outcomes fifteen months after treatment begins. How DUP can best be defined and measured so that it reliably predicts later outcomes. Results may provide evidence for whether early-detection services improve timely access to care and whether reducing the duration of untreated psychosis contributes to better long-term functioning. The study may also help establish clearer international standards for how DUP should be measured in both research and clinical practice.

The proposed research will test the hypothesis that objective social isolation and loneliness are linked to neurobehavioral mechanisms involved in social perception and motivation in individuals with and without serious mental illness. Moreover, it will investigate the specific dynamic interactions among these experiences in daily life and how they, and their neurobehavioral predictors, are linked to day-to-day functioning. The findings of this project could provide novel targets for therapeutics aimed at improving functioning and overall quality of life in individuals with serious mental illnesses, as well as quantitative phenotypes for use in early detection efforts.

The goal of this case series study is to learn if culturally-adapted cognitive-behavioural therapy is practical, acceptable and safe among Black Sub-Saharan African and Caribbean people experiencing psychosis. The main question it aims to answer is: Is culturally-adapted CBT for psychosis feasible, acceptable to and safe for Black Sub-Saharan African and Caribbean people experiencing psychosis? Participants will be asked to: * Answer some questionnaires about how things are at the moment * Attend up to 16 sessions of therapy * Answer the same questionnaires to see what has changed, if anything * Complete a semi-structured interview about their expectations and experience of therapy

The primary objective of this study is to evaluate the efficacy of Mentalization-Based Treatment (MBT) combined with Need-Based Clinical Interventions (NBCI) compared to NBCI alone, on CHR-P diagnostic statuses and symptom expression (Hypothesis 1). Specifically, the investigator will assess diagnostic outcomes using a 3-level variable: transition to psychosis, CHR-P status quo, and remission out of CHR-P, as well as CHR-P symptom expression. The investigator hypothesize that: (1a) the experimental treatment (MBT + NBCI) will have a significant effect on diagnostic status (i.e. transition to psychosis) at the end of treatment and follow-up; (1b) the experimental treatment (MBT + NBCI) will significantly reduce the severity of psychotic symptoms at the end of treatment and follow-up.

The purpose of this study is to evaluate KarXT + KarX-EC as a treatment for psychosis associated with Alzheimer's disease.

Participants will complete one online intervention lasting 12 weeks. Each week, they will be asked to complete a 20-30 minute session online. The intervention is targeting improved mood and positive affect in order to support increases in motivation and goal-directed behavior. Before and after the intervention, participants will be asked to complete measures to assess symptoms, mood, and behavior.