Schizophrenia Disorders

This observational study will characterise the general psychiatric and general medical phenotypes of 100 adults, sequentially admitted to NHS General Adult Psychiatry (GAP) "mental health" inpatient wards, providing the first detailed information on morbidity in this patient population.

Study to evaluate the safety and tolerability of single ascending doses of brexpiprazole long-acting injection in healthy subjects/patients with schizophrenia.

This is a prospective, randomized, interventional study designed to evaluate the efficacy and safety of SEEG-guided deep brain stimulation (DBS) for symptom improvement in patients with treatment-resistant schizophrenia. Using stereo-electroencephalography (SEEG) to record brain activity, we will identify specific abnormal electrophysiological targets and signal features associated with clinical symptoms, followed by a 12-month open-label stimulation period. The study is conducted in three stages: Stage 1 consists of SEEG brain mapping, screening of intervention targets, and optimization of stimulation parameters; Stage 2 consists of DBS implantation surgery and further optimization of stimulation parameters; Stage 3 is a randomized crossover treatment phase, followed by an open-label treatment period.

This study aims to investigate whether specific non-coding RNAs, molecules involved in the regulation of gene expression, are altered in individuals with psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, panic disorder, and obsessive-compulsive disorder. Researchers will compare the expression levels of these molecules in patients who are drug-naïve or have been free from psychiatric treatment for at least six months with those observed in healthy volunteers. The study will also evaluate whether the expression of these non-coding RNAs changes after approximately five months of standard psychiatric treatment. Blood samples collected during routine clinical care will be used to measure the expression levels of selected non-coding RNAs using reverse transcription quantitative polymerase chain reaction (RT-qPCR), a laboratory technique used to assess gene expression. This is an observational study and does not assign specific treatments. All therapies will be prescribed according to standard clinical practice. The main objective is to determine whether alterations in non-coding RNA expression may serve as biological markers of psychiatric disorders and whether these markers may help monitor treatment-related changes over time. The findings may contribute to a better understanding of the biological mechanisms underlying major psychiatric disorders and support the future development of more accurate diagnostic and therapeutic approaches.

Schizophrenia, affecting 1% of the population, is a persistent disorder characterized by varied symptoms. Antipsychotic medications effectively address positive symptoms (delusions, hallucinations) and relapse but have limited impact on negative symptoms (e.g., blunted affect, anhedonia) and cognitive impairment. These dimensions significantly influence social functioning and quality of life. Combining non-pharmacological approaches like Cognitive Remediation (CR) and psychosocial rehabilitation alongside antipsychotic drugs is recommended to enhance overall functioning and quality of life. Current CR programs show moderate effectiveness due to patient commitment issues. However, completed programs demonstrate higher efficacy. Real-life applicability of these programs lacks sufficient data. We propose musical learning for cognitive remediation due to its established cognitive benefits in the general population, targeting executive functions, working memory, attention, and inhibition. These functions are specifically impaired in schizophrenia and thus are relevant for remediation. Though unexplored in schizophrenia, music learning seems promising due to its motivational and pleasurable aspects for long-term commitment and its transferability through embodied and situated dimensions. A pilot study (ARCoS-1) on CR by musical learning demonstrated feasibility and preliminary positive results on cognitive and negative symptoms. This project aims to assess this method's effectiveness on a larger scale. Our hypothesis posits that musical learning offers an efficient and well-received medium for CR in patients with schizophrenia.

The goal of this clinical trial is to learn whether learning and belief updating change in response to the treatment of persecutory delusions, in individuals with schizophrenia-spectrum disorders. The main questions are: 1. do prior expectations about environmental volatility reduce following effective psychotherapeutic treatment of delusions? 2. does corresponding brain activity related to volatility change with effective treatment of delusions? Participants will: 1. engage in CBTp or TAU + phone check-ins for 16 weeks 2. complete assessments at 4 timepoints over the course of 6 months 3. complete an MRI when possible

Schizophrenia spectrum disorders (SSDs) have a significant trauma etiology: trauma has been reported in 65 - 80% in this patient group and have a negative impact on prognosis. Trauma treatment is currently not offered in SSDs due to a lack of evidence. KIT is a pragmatic trial comparing the effectiveness of added trauma focused therapy, Eye Movement Desensitization and Reprocessing (EMDR) to standard treatment in SSDs. The study will compare EMDR as add on to treatment as usual (TAU) to TAU in patients with schizophrenia spectrum disorders (SSDs). The overall aim is to examine the effectiveness of EMDR on trauma symptoms in SSDs. Participants will receive max. 26 sessions of EMDR, and complete assessments before, during and after the course of therapy, in addition to a period of time (6 months) after therapy to examine long-term effects.

Schizophrenia - marked by delusions, hallucinations, and cognitive deficits - causes the most disability of any mental health condition, but existing treatments have significant side effect burden and are often ineffective. Disordered neural activity in the hippocampus likely contributes to schizophrenia symptoms, but to develop better therapies we need to understand whether hippocampal activity in schizophrenia can be systematically affected by non-invasive brain stimulation techniques like transcranial magnetic stimulation (TMS). This proposal will investigate the use of connectivity-guided theta burst brain stimulation to specifically target hippocampal function in schizophrenia, offering insights into fundamental hippocampal processes, schizophrenia pathophysiology, and potential avenues to use brain stimulation as a therapeutic tool in this devastating illness.

Schizophrenia spectrum disorders are associated with impairment in the microstructure of white matter, the key brain tissue responsible for fast communication between different brain regions necessary for any complex task. This white matter impairment is linked to problems with cognition in schizophrenia, especially slower processing speed. This project aims to study the potential for correcting white matter deficits in schizophrenia by examining mechanisms underlying white matter structure changes in response to training on playing a mock musical instrument.

Schizophrenia is a condition that causes symptoms like delusions, hallucinations, reduced motivation and muddled thinking. It is a common, severe and disabling psychiatric illness affecting about 1/100 (1%) of people. It is ranked the third most disabling illness worldwide. Six in seven patients do not recover from the illness in 6-12 months and continue to experience psychotic symptoms. Therefore, there is a strong unmet need for new evidence-based treatments to target the neurobiology underlying schizophrenia. There is increasing evidence to indicate that glutathione (GSH), the main brain antioxidant, is abnormal in schizophrenia and may provide a new treatment target. In this study, the investigators plan to determine whether Diroximel Fumarate (DRF) (currently a treatment for a brain disorder called multiple sclerosis) can increase GSH in the brain of patients with schizophrenia using a brain scan (MRI) and explore whether changes in GSH are related to other brain measures (measured with MRI and EEG- which measures electrical activity in the brain), blood markers of GSH, and symptoms. During this study 30 people with schizophrenia will be recruited. Participants will take the drug DRF for two weeks, a computer will then decide randomly whether each person will continue to take DRF or a placebo/dummy pill for another two weeks. During this part of the study neither the patients nor the researchers will know which type of drug the patient is taking. Brain GSH and the other measures described will be assessed before and after taking the DRF and placebo/dummy pill. At the end of the study (2027), the investigators will see if taking DRF alters the brain chemical (GSH) in people with schizophrenia and whether this is linked to other measures and symptoms. It will also give researchers information about the best way to design future studies for patients with schizophrenia using this drug.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for the treatment of type 2 diabetes and obesity, have shown promise as a novel treatment for alcohol use disorder (AUD). This study aims to investigate whether the Glucose-dependent Insulinotropic Polypeptide/GLP-1RA tirzepatide will reduce alcohol consumption in patients with a dual diagnosis of AUD and schizophrenia, a population in dire need of improved treatment options. To further investigate the neurobiological underpinnings of a potential dampening effect on alcohol consumption, functional magnetic resonance imaging (fMRI) brain scans will be applied. The key anticipated outcomes include: * decreased alcohol consumption and * reduced alcohol cue-induced brain activity in the GIP/GLP-1-treated patient group compared with the placebo group. To the best of the investigators knowledge, this has never been examined before.

The purpose of this study is to evaluate the effectiveness of a psychosocial intervention called iTEST for people with psychotic disorders that targets introspective accuracy, or the ability to accurately gauge ones abilities. iTEST combines daily cognitive training on a mobile device with coaching that addresses recovery goals. In this trial, we will randomize people to one of two interventions conditions, iTEST or a control condition that receives coaching and cognitive training that does not emphasize introspective accuracy. Both interventions will take place over 12 weeks and participants will be asked to complete assessments at baseline, 6 weeks, 12 weeks, and 24 weeks. The primary outcome of the study is community functioning. Participants will be from three metropolitan areas: San Diego, Dallas, or Miami.

This study aims to identify novel markers of psychosis using electroencephalography (EEG).

This observational study aims to provide new insights into the nature and classification of severe mental illness and dementias that in time should help improve diagnostic practise, and enable the development of new and improved treatments. The investigators will achieve aims by gathering information and biological samples from over 50,000 research participants and then linking this information with participants' electronic health records, genetic and other potential markers of mental illnesses (called biomarkers, derived from biological samples). The investigators will use this resource to analyse how potential risk factors - genetic, other biological and non-biological (related to the participants' life circumstances) - influence participants' experiences, symptoms, and outcomes (both mental and physical health). The investigators will also use advanced analysis to assess whether there may be better ways of grouping together and understanding the experiences of those with severe mental illnesses and dementias. Given the value and importance of this resource for advancing mental health research, the investigators will also make the data available to other researchers to pursue these broad research aims.

This study aims to evaluate the relationship between cognitive, metacognitive and social cognition variables in patients with psychosis undergoing VR-based Avatar Therapy for the treatment of auditory hallucinations. In addition to the primary intervention, participants will be assessed using validated tools for emotion recognition, attributional style, theory of mind, neurocognition, and metacognition. The study also explores the potential role of trauma as a predisposing factor. Assessments will be conducted at four time points: screening (week 0), baseline (week 12), intervention period (weeks 12-24), and post-therapy follow-up (week 24). By investigating these variables, this study seeks to better understand their impact on treatment outcomes and contribute to the development of personalized therapeutic approaches.

This is a study investigating how brief online activities can influence mood and attitudes.

Disorganized speech, language and communication, also called 'formal thought disorder,' is a key part of severe mental illnesses like psychosis and mood disorders. When someone's communication is disorganized, it makes social interactions difficult, increases stigma and affect educational and employment opportunities. However, we do not know much about why this happens. This project, called DIALOG, aims to understand the brain's role in disorganization by studying everyday language use instead of traditional clinical ratings. The study will look at how our brain creates predictions during interactions and how these processes break down in psychosis. This international project also includes experts with personal experience of mental illness. The study will look at speech, thinking patterns, symptoms, and brain waves. The goal of the study is to see if brain waves are disrupted in psychosis, especially in language-related problems. Speech tasks, like describing pictures, talking about a significant event, and telling a story are administered. These tasks will be audio-recorded for analysis. Non-invasive brain imaging technologies such as Magnetoencephalography (MEG) and Magnetic Resonance Imaging (MRI) are utilized. MRI creates images of the brain's structure, while MEG records magnetic activity from neurons, shown as brain waves. The MRI machine uses a large magnet to create images, and MEG captures small magnetic field changes from brain activity. Participants will also undergo clinical and neurocognitive assessments. The study will combine Large Language Models (LLM) applied to speech recordings with large scale participant data from neuroimaging tools (MRI/MEG). The goal of DIALOG is to pioneer a computationally informed, molecular-to systems-level account of disorganisation, identifying the precise mechanisms that can be targeted with novel treatments. This project aims to gather speech and neuroimaging data from Montreal \[100 healthy volunteers and 50 patients with psychosis\], Groningen \[17 synaptic density PET scans\], Cardiff \[600 participants\] and Marburg \[1600 participants\] with schizophrenia, schizoaffective disorder or mood disorders and user acceptability data at Pavia and Melbourne.

This multimodal study explores the mechanisms underlying social dysfunction in individuals with schizophrenia. It focuses on the relationship between disorganized communication and social interaction, aiming to identify measurable markers of disorganized communication and link them to clinical symptoms and social functioning. Key Research Questions: How do neural and behavioural synchrony contribute to social impairments in schizophrenia? What roles do interbrain synchrony, motor imitation, reaction time, and verbal coherence play in disorganized communication? Participants will: 1. Engage in structured and semi-structured real-time social interactions while undergoing dual-brain electroencephalogram (EEG) hyperscanning to measure neural and behavioural activity. 2. Perform nonverbal tasks such as motor imitation and reaction time assessments to investigate coordination and behavioural synchrony patterns. 3. Participate in a clinical interview that evaluates verbal production, thought coherence, and speech organization. By combining these assessments, the study aims to advance our understanding of how social and communication impairments manifest in schizophrenia. The findings will contribute to developing improved diagnostic tools and targeted interventions, ultimately supporting patients in achieving better social functioning and quality of life.

This study aims to determine whether Cognitive Remediation Therapy (CRT) can improve attention, memory, and emotional regulation in people with schizophrenia. CRT is a structured program that includes exercises to strengthen cognitive skills such as problem-solving, working memory, and emotion regulation. The study will recruit 60 participants: 30 individuals with schizophrenia and 30 healthy individuals of similar age and gender. Those with schizophrenia will be randomly assigned to either receive CRT or be placed on a waitlist without therapy. All participants will undergo non-invasive brain activity (EEG) and emotional response (GSR) recordings before and after the therapy. The study's main question is: Does participating in a 12-week CRT program improve brain-based markers of attention and emotional regulation in people with schizophrenia? Additional tests, such as memory and emotion recognition tasks and self-report questionnaires, will help assess changes in thinking skills and emotional well-being. The study may help better understand how CRT affects both brain function and quality of life in schizophrenia.

The study design is a de-escalation of current atypical AP treatment to X/T at a maintenance dose of X/T established either at 100 mg xanomeline/20 mg trospium chloride BID (total daily dose 200 mg xanomeline/40 mg trospium chloride) or 125 mg xanomeline/30 mg trospium chloride BID (total daily dose 250 mg xanomeline/60 mg trospium chloride) based on participants' clinical response and/or tolerability. While the package insert for X/T provides guidance for clinicians on dosing, this study is designed to assess how transitioning will occur in the "real world" situation.

Rationale: Ethnic minorities and asylumseekers have a two- to three-times increased risk of psychosis compared to people from their host country. Among patients experiencing psychosis, paranoid delusions are a common symptom. Diagnostic assessments are challenging in this group because of language differences and sociocultural differences in interpersonal social behavior and communication. To fill this gap this research will make use of Virtual Reality (VR) to assess thoughts, behaviours and emotions in real-time. VR has a high ecological validity and its partial non-verbal nature has a clear potential in terms of a transcultural application among asylumseekers. Objective: The main objective of this study is to discover how asylumseekers with a psychotic disorder who are experiencing paranoid delusions behave and evaluate threat in a virtual environment. Secondary objectives: To assess the suitability and applicability of using VR within the specific population of asylumseekers with a psychotic disorder and paranoid delusions. Study design: The study uses a mixed-methods design, combining qualitative phenomenological data and descriptive quantitative data. Study population: Adult psychiatric patients that are seeking asylum in the Netherlands with a DSM-5 classification of a psychotic disorder and paranoid delusion (as measured by the PANSS) will be included. Furthermore, patients must receive mental health care from CTP Veldzicht, either in one of the wards (closed or open) or through ambulatory care. Intervention: The patients will be immersed in a VR-environment using a head mounted display. Four different VR-scenarios are used, each taking up three to four minutes. Using simple movement instructions, patients are asked to walk around and observe their environment. Main study parameters/endpoints: Phenomenological semi-structured interview. The interview measures the experience of participants in a qualitative matter. Audio recordings of the semi-structured interviews will be transcribed. These transcriptions containing rich qualitative data are the main study parameter. Additional descriptive qualitative data (demographic \& symptom specific) will be gathered through questionnaires to provide quantitative insight in the sample-population (questionnaires used: PANSS, SSPS, SBQ, and VAS). Subsequently, psychiatrists working in the field of transcultural psychiatry will be interviewed about the paranoid behaviour of participants based on video and audio recordings of the VR-session. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Some participants might experience simulator sickness symptoms. No major adverse events are expected or have been documented in previous VR studies of our research group using the same VR hardware and software. The assessment will take approximately 90 minutes in total. No benefits are expected. An empathic and transparent approach, a clear consent procedure, close monitoring of participants' moods and consistently adverting an opt-out will be used.

In schizophrenia, an abnormal reduction in neuronal gamma oscillations (30-100 Hz) is associated with negative symptoms such as cognitive dysfunction. The literature suggests that rescuing gamma oscillations through non-invasive brain stimulation may be an accessible and safe add-on strategy to mitigate negative symptoms. Here, a stimulation protocol based on gamma visual stimulation will be tested. This pilot study will follow an uncontrolled clinical trial design: A minimum of ten patients diagnosed with schizophrenia or a schizoaffective disorder and predominant negative symptoms will be recruited at Klinikum rechts der Isar. They will undergo a multisession stimulation protocol, consisting of one hour of 40 Hz visual stimulation per day over five consecutive days, during which they will be encouraged to fall asleep. An equal number of patients will be recruited for a treatment-as-usual group without intervention. Pre- and post-assessments will include EEG, a cognitive test battery (THINC-IT), a mood scale (PANAS), and a schizophrenia symptom scale (PANSS). This study's results will inform on the feasibility of gamma visual stimulation as a potential add-on intervention in schizophrenia.

Schizophrenia is a chronic, recurrent and disabling illness that usually lasts a lifetime and causes serious problems in quality of life and functioning. Psychoeducation programmes added to drug treatment in the treatment of schizophrenia have been shown to increase the knowledge of patients and their relatives about the disease, coping skills, prevention of exacerbations and relapses of the disease, social functioning, insight into the disease, compliance with drug treatment and quality of life. Rehabilitated individuals diagnosed with schizophrenia who are registered and continuing at Kastamonu Training and Research Community Mental Health Centre will constitute the population, and individuals who continue between April 2024 and May 2024 will constitute the sample. The research will be conducted with schizophrenic patients in a pre-test-post-test, experimental and control group experimental design. Power analysis will be performed to determine the number of people to be sampled and calculated with the G\*Power 3.1 programme. 40 people will be reached in the groups, 20 people in the experimental group and 20 people in the control group. In the evaluation of the data, descriptive statistical methods (Mean, Standard deviation) as well as the correlation test will be used to evaluate the relationship between the average scores before and after the training in the comparison of quantitative data. Wilcoxon related sample test will be used to make comparisons before and after the training. Personal Information Form, Internalised Stigma Scale in Mental Illness (ISIS) and Healthy Lifestyle Behaviours (HBSB) scale will be used to collect the data. Awareness-based psychoeducation programme will be applied to the experimental group. The aim of psychoeducation is to create a change in knowledge and behaviour towards healthy lifestyle behaviours (1- Self-actualisation, 2- Health responsibility, 3- Exercise, 4- Nutrition, 5- Interpersonal support, 6- Stress management) by reducing internalised stigma. Therefore, it will be evaluated whether the applied psychoeducation programme creates the intended change in knowledge and behaviour. This study will be conducted to examine the effect of a 6-week 12-session self-awareness-based psychoeducation programme given to schizophrenia patients on internalised stigma and healthy lifestyle behaviours. In this study, schizophrenic patients will be provided with regular psychoeducation to provide individual support, to ensure the development of coping skills for self-protection, and to gain knowledge and skills to gain a healthy lifestyle. After the prepared psychoeducation, a training guide will be created for the participants and will be given after the training, thus ensuring continuity of education.

Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by cognitive decline, social withdrawal, and positive symptoms such as hallucinations and delusions. Research suggests that SCZ and schizotypy exist along a continuum, with shared structural and behavioral abnormalities, the latter of which encompass the sensory and perceptual domain, often in the form of altered multisensory integration, as seen in tasks like the Sound-Induced Flash Illusion (SIFI). Individuals with schizotypal traits or SCZ show enlarged temporal binding windows (TBW) of cross-modal integration, affecting perceptual accuracy and multisensory judgments. However, whether these deficits stem from overactive top-down modulation or weakened bottom-up sensory precision remains unclear. The current study seeks to address these questions, by asking participants (healthy individuals screened as for their schizotypal traits, and patients suffering from SCZ) to complete a modified version of the SIFI, as well as an audiovisual temporal order judgment (TOJ) task. Cross-modal performance will be assessed via signal detection theory (SDT) metrics and psychometric modeling to estimate individual TBWs, thereby assaying audiovisual processing abilities along the schizotypal continuum

Offspring of parents with bipolar disorder (BD) and schizophrenia (SZ) are vulnerable and at high risk for these disorders. Despite the fact that positive family history of SZ or BD is the strongest predictor for the development of these severe mental illnesses, there is limited evidence assessing young adults of SZ and BP simultaneously with lack of detailed handling of similarities in risk and developmental trajectories during adolescence