Schizo-affective Disorder

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.

Although antipsychotic is effective for schizophrenia, however, still certain proportion of patients were not responsive to treatment. Treatment resistant schizophrenia (TRS) is accompanied by function decline and heavy burden. In recent decades, the biological mechanism of schizophrenia extended from dopamine theory to the role of glutamate system. This shift could be an alternative pathway to developing the treatment of TRS. Sodium benzoate (SB) could be an option as a glutamatergic agent for the patients with TRS. However, most evidence of SB is for treating patients with schizophrenia and other mental disorders but the evidence for treating patients with TRS is scarce. To predict the treatment response of SB will be an urgent topic in the future. Little is known about the precise medicine for treating patients with TRS. The present project will extend our pilot randomized clinical trial on SB for TRS. A total of 90 patients with TRS will be enrolled from three centers and will be assigned to 8 weeks of treatment with SB or placebo (2:1). A comprehensive battery of potential markers will be employed, including 1H- magnetic resonance spectroscopy (MRS), brain functional connectivity, genotyping, immune biomarkers, cognitive function, and clinical characteristics. The efficacy of SB on TRS will be confirmed in this project. Predictors for treatment response will be identified. Artificial intelligence algorithms will be used for probing the feasibility of precision medicine.

A new mental health application will be developed for persons with schizophrenia and schizoaffective disorder. The aim is to look at whether it is feasible to use a mobile health application for improving medication adherence in persons with schizophrenia and schizoaffective disorder and whether it is acceptable to that population.

To study the effect of adjunctive bazedoxifene - a selective estrogen receptor modulator (SERM) in a double blind, placebo-controlled adjunctive study in the treatment of women with schizophrenia. All patients receive standardized antipsychotic medication.

1. The purpose of this study is to evaluate the safety and feasibility of transcranial ultrasound stimulation (TUS) treatment in patients with schizophrenia. Subjects are individuals diagnosed with schizophrenia who will receive non-invasive, low-intensity pulsed ultrasound stimulation targeting the hippocampus and its surrounding regions. Evaluations will be conducted before and after the treatment sessions, including electrocardiograms (ECG), blood biochemistry tests, psychiatric symptom assessments, depression level assessments, and cognitive function assessments. 2. The primary objective is to assess the safety of this intervention in patients with schizophrenia. The secondary objective is to explore whether the current stimulation parameters may lead to improvements in the assessed symptoms. Ultimately, this study aims to support the future application of low-intensity pulsed ultrasound as a potential intervention to alleviate symptoms of schizophrenia and improve patients' quality of daily life.

This 16 week clinical trial investigates a precision-medicine approach to schizophrenia by targeting a biologically distinct subgroup,-approximately one-third of patients-characterized by the presence of anti-gliadin antibodies (AGA IgG+) which is associated with elevated inflammation in the IL-23/IL-17 immune axis (Th17 pathway). This specific biotype is associated with pronounced negative symptoms, cognitive deficits, and reduced white matter integrity. Building on evidence that this pathway can be modulated to improve clinical outcomes, we are conducting a randomized, double-blind clinical trial of mirikizumab, an FDA-approved monoclonal antibody targeting IL-23, in addition to current antipsychotics, in schizophrenia patients who are positive for AGA IgG. The primary objective is to determine whether mirikizumab - a repurposed FDA approved monoclonal antibody treatment inhibiting IL-23-- will be superior to placebo in treating experiential (e.g., anhedonia and asociality) negative symptoms and cognitive impairments. Secondary aims will be to assess changes in T-cell subtypes and relative abundance by gene expression, peripheral cytokines, and neuroimaging markers (in a smaller subset). By focusing on this patient subgroup, who are identified by their immune status, the research aims to provide a targeted, revolutionary treatment for symptoms that have traditionally remained resistant to standard antipsychotic therapies. This protocol includes a screening phase, with a separate consent form which is intended to identify those with AGA IgG antibodies. This screening portion will also serve to compare other aspects of immune functioning and the TH17 pathway between patient groups and controls in order to further characterize and show that Th17 (and similar immune cell lines) are different between AGA IgG positive, AGA IgG negative and healthy controls of either status.

The main question this study is trying to answer is whether lumateperone, an FDA-approved antipsychotic drug, can help reduce possible side effects of clozapine, such as weight gain and elevated levels of sugar and bad cholesterol. Participants will be randomly assigned to either take lumateperone (Caplyta) or a placebo for 12 weeks, in addition to their regularly prescribed clozapine. During their participation, patients will answer questions about their psychiatric and daily functioning, have blood drawn, and have their body composition analyzed (similar to stepping on a scale).

The purpose of this study is to understand how different types of community-based mental health care affect thinking abilities, daily functioning, and brain activity in adults with schizophrenia and related conditions. The investigators are especially interested in learning whether the Clubhouse Model-a structured, supportive community for individuals with mental illness-has unique benefits compared to standard outpatient mental health services. If participants decide to join, they will be asked to complete a total of six study visits with the research team over the course of your participation. Three of these study visits are at the beginning (baseline) and the remaining three are six months later. Two of the three visits will includes interviews, questionnaires, and thinking and memory tasks (cognitive testing) and one session will be an MRI brain scan, which is a safe and non-invasive imaging procedure. The total time required for each visit will be approximately 90 minutes to two hours. Participants may take breaks as needed.

Individuals living with a psychotic disorder often experience changes to their thinking and social skills that can lead to challenges with work, school, relationships and living independently. One intervention to target these areas is cognitive remediation therapy, which can be delivered in virtual reality to help apply the skills and strategies learned to day-to-day life. Over the past few years, our team has co-developed a cognitive remediation program in virtual reality with healthcare professionals and people with lived experiences of psychosis. The current trial tests the feasibility and efficacy of this cognitive remediation program in virtual reality at improving thinking skills, social skills, and daily life functioning.

This is a study of the efficacy and safety of BXCL501 in children and adolescents with acute agitation and either bipolar disorder or schizophrenia.

This is a double blind adjunctive randomized controlled trial for schizophrenia using acetazolamide.

This is a double blind adjunctive randomized controlled trial for schizophrenia using cromoglicate.

This study investigates the ability of transcranial direct current stimulation (tDCS) applied over the motion processing area of the brain (area MT) to improve face emotion recognition (FER) ability. tDCS is a type of non-invasive brain stimulation in which low level currents are applied over the scalp to influence underlying brain function. In schizophrenia, impaired ability to detect facial motion has been shown to contribute to impaired FER, which, in turn, leads to difficulties in social cognition and poor social outcome. The study will use both fMRI and EEG to measure brain function while participants view moving dot and dynamic face stimuli. Analyses will compare changes in fMRI and EEG activity in individuals receiving active vs. sham stimulation.

The goal of this clinical trial is to identify the specific characteristics (phenotypes) that may be useful to help select the right medication for weight loss, and to study the effect of individualized guided medication in patients with bipolar disorder ages 18-65. The main questions it aims to answer are: * Can the investigators compare the distribution of obesity characteristics (hungry brain, hungry gut, emotional hunger) between bipolar patients and non-bipolar participants (comparing from IRB #24-002375)? * Can the investigators evaluate the feasibility of anti-obesity medication (AOM) in patients with bipolar disorder? Participation will last for about 20 weeks and includes 8 in-person study visits, up to 11 phone call visits, and 13 virtual group therapy sessions. The first visit lasts about 2 hours and includes going over the informed consent form, a diagnostic interview to confirm diagnosis, gathering vital signs, mood questionnaires, an ECG, a blood draw, and urine drug and pregnancy tests (if applicable). The second visit lasts about 6-7 hours and involves multiple procedures and completing questionnaires to determine which study drug would allow participants to lose weight most effectively. At the third visit, participants will be assigned to take one of three FDA approved medications for weight loss: Semaglutide (Wegovy®), Naltrexone/Bupropion (Contrave®), or Phentermine/Topiramate (Qsymia®). It is possible that participants could be assigned to a group that receives no study medication. All participants will be enrolled in a 12-week virtual group therapy program targeted for weight loss. On this third visit the investigators will also gather vital signs, and participants will give a sample of blood. After the third visit, participants will come in for study visits every 4 weeks for 20 weeks (5 visits) to assess medication adherence, vitals, and answer questions about mood and eating (participants will also give a sample of blood at the 8-week and 20-week visits). For participants assigned to a study medication, the study team will call every week for the first 2 months (excluding in-person visit weeks) to assess mood and safety. After the first 2 months, the study team will call the participant every two weeks in between in-person visits. Participants will be compensated for time spent in this study. Participants assigned to a study medication will also be given the option to participate in the open-label phase of the study, which involves 3 follow-up visits (weeks 24, 36, and 48) over 7 months after the 20-week trial. During this phase, participants can continue to take the medication through their clinical care provider.

This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study how hallucinations work in schizophrenia. TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study the investigators will be stimulating the brain to learn more about how TMS might improve these symptoms of schizophrenia.

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

This protocol proposes an initial randomized clinical trial that includes all patients with suicidal ideation (SI) at baseline, and with SI as the primary outcome measure to examine whether Right Unilateral Low-Amplitude Pulse - Seizure Therapy (RUL LAP-ST) treatment has more magnitude and rate of remission of SI as conventional pulse amplitude Right Unilateral Electroconvulsive Therapy (RUL ECT) (based on our prior secondary analysis). Our central hypothesis is that RUL LAP-ST has significantly less cognitive/memory side effects (no memory side effects were noted in our prior studies for 500mA and 600mA) and thus is more favorable in terms of side effects compared to RUL conventional pulse amplitude ECT, while maintaining better anti-suicidal effect.

The goal of this clinical trial is to examine if iTBS applied to the DMPFC improves social cognitive performance compared to sham stimulation in people diagnosed with schizophrenia, schizoaffective disorder, schizophreniform disorder, or psychotic disorder not otherwise specified. The main objectives of this trial are: * Compare changes in social cognitive performance between the active vs. sham treatment groups * Compare changes in social cognitive network functional connectivity between the active vs. sham treatment groups Each participant will receive iTBS (active or sham) five days per week for four consecutive weeks. Functional magnetic resonance imaging (fMRI) scans, clinical assessments, and cognitive tests will be performed at pre-treatment, post-treatment, and 6 months after the completion of treatment.

The current study examines the efficacy of a cognitive training intervention for improving emotion regulation in psychotic disorders. it is hypothesized that the cognitive training program will enhance prefrontal activation, leading to enhanced emotion regulation.

There is increasing awareness of the importance of providing mental health services and support that promote a recovery-oriented and human rights-based approach. A mental health service system that is guided by a rehabilitation and recovery perspective places emphasis on treating the consequences of the illness rather than just the illness "per se", and on empowering people to regain control of their identity and life, and to have hope for the future. Within this philosophy, mental health policies in several countries advocate for the introduction of peer workers in mental health services, people with lived experience of mental health issues and recovery, who are employed to use their lived experience to support those who access mental health services. However, more effectiveness and implementation research is needed. Evidence also suggests that the period following hospital discharge is of high risk of treatment dropout for people with serious mental illness, thus interrupting their recovery process. Therefore, this vulnerable population may particularly benefit from more targeted interventions during this transitional period. The research project will conduct a pilot randomized controlled trial to evaluate the feasibility, implementation and potential effectiveness of the Critical Time Intervention-Peer Support model, a recovery-oriented based model for people with serious mental illness discharged from inpatient psychiatric treatment facilities in Portugal. The randomized controlled trial (RCT) will be conducted in three psychiatric services in the Lisbon Metropolitan Area and their catchment areas. People with diagnoses of psychotic disorders discharged from inpatient psychiatric treatment facilities will be recruited and randomly divided into CTI-PS intervention or usual care. Those allocated to the intervention group will additionally receive CTI-PS rather than usual care alone over a 9-month period. Outcomes at baseline, 9- and 18-months will be analyzed by multilevel models, considering the observations clustered within sites. Longitudinal analyses will be used to examine trends over time of the outcomes of interest. The implementation of the CTI-PS model will introduce a novel approach to community mental health care that has not yet been tried in Portugal. This study aims to explore to what extent this intervention can be effectively implemented in countries with the characteristics of Portugal. Additionally, the proposed research aims to contribute to the global knowledge about peer interventions by exploring whether the CTI model can maintain its effectiveness using peers.