
Links Between Perception of Temporal Order Judgment and Causality in Schizophrenia
SchizophreniaPeople with schizophrenia show disturbances in the perception of time. Among these alterations are the perturbations of the temporal order judgment. They are characterized by the fact that, as opposed to the general population, people with schizophrenia require a longer time interval between two successive stimuli to estimate which of the two events appeared first. If these alterations are now well documented, their consequences remain little explored. Among these consequences could however appear distortions of the judgment of causality (likely to underlie certain delusional interpretations) as well as a distressing experience of loss of the continuity of the lived experience (that could contribute to the alterations basic of self-awareness).

Reactivity of the Vestibular System to Caloric Vestibular Stimulation in Schizophrenia
SchizophreniaHealthyThis study aims to determine if individuals with schizophrenia have greater reactivity to vestibular stimulation than healthy controls. The physiological response of vestibular stimulation will be assessed with electronystagmography, which provides a measure of the intensity of the nystagmus via PSPV. Positive results would suggest greater vestibular system reactivity to vestibular stimulation may be a biomarker of schizophrenia. Pathophysiologically, increased vestibular reactivity to vestibular stimulation may reflect abnormal vestibular function or impaired central suppression of the vestibular ocular reflex.

Imaging Cannabinoid Receptors Using Positron Emission Tomography (PET) Scanning
SchizophreniaCannabis Dependence5 moreThe aim of the present study is to assess the availability of cannabinoid receptors (CB1R) in the human brain. CB1R are present in everyone's brain, regardless of whether or not someone has used cannabis. The investigators will image brain cannabinoid receptors using Positron Emission Tomography (PET) imaging and the radioligand OMAR, in healthy individuals and several conditions including 1) cannabis use disorders, 2) psychotic disorders, 3) prodrome of psychotic illness and 4) individuals with a family history of alcoholism, 5) Post-Traumatic Stress Disorder 6) Opioid Use Disorder using the PET imaging agent or radiotracer, [11C]OMAR. This will allow us to characterize the number and distribution of CB1R in these conditions. It is likely that the list of conditions will be expanded after the collection of pilot data and as new data on cannabinoids receptor function and psychiatric disorders becomes available. Those in the cannabis us disorder arm of the study will have a PET scan on at least three occasions: once while smoking as usual, once after 48-hours of abstinence from cannabis, and a final time after 4 weeks of abstinence. Additional scans may be conducted within the 4 weeks and the last scan may be conducted well beyond 4 weeks. Similarly, while most schizophrenia patients may get scanned just once, a subgroup of patients may get scanned more than once. For example to tease out the effects of medications, unmedicated patients may get scanned while unmedicated and again after treatment with antipsychotic medications. Similarly prodromes may get scanned while in the prodromal stage off medications, on medications and after conversion to schizophrenia.

Functional Relevance of Dopamine Receptors in Healthy Controls and Patients With Schizophrenia:...
Schizoaffective DisorderSchizophreniaBackground: Some illnesses, such as schizophrenia, have effects on brain cells called dopamine receptors, which are required for normal brain function. People with schizophrenia have difficulty thinking and experience hallucinations and delusions. Medications that change brain dopamine receptors can decrease these hallucinations and delusions. The cause of schizophrenia and its association with brain dopamine receptors is not known but may be clarified by studying dopamine receptors in people who have dopamine disorders (such as schizophrenia) and those who do not. Researchers are interested in studying the dopamine system to gain a better idea of how dopamine disorders develop, which may lead to better medical care for people with schizophrenia. Objectives: - To study the amount and distribution of two types of dopamine receptors. Eligibility: Individuals between the ages of 18 and 60 who have schizophrenia. Healthy volunteers between the ages of 18 and 90. Design: Participants will undergo a full screening, with physical and psychological history, a neurological examination, and blood and urine samples. Participants will have a blood flow map of the brain recorded with a positron emission tomography (PET) brain scan. A magnetic resonance imaging (MRI) scan will also be performed to determine brain anatomy. To study the amount and distribution of dopamine receptors in the brain, participants will receive a small amount of a radioactive chemical in the vein, followed by a PET scan. The procedure will be performed twice in two separate sessions, once for [18F]fallypride and once for [11C]NNC-112.

Cannabis and Thought Disorder in Schizophrenia
SchizophreniaRecent studies have suggested a strong relationship between cannabis use and the level of thought disorder in subjects with schizophrenia. Moreover, the level of thought disorder has been associated with an increased functional connectivity between the temporal lobe and the Putamen. However, the brain mechanisms underlying these two relationships are still poorly known. Better understanding these mechanisms is important to improve patients' care, in particular among treatment-resistant patients. The objective of the CANDI study consists of assessing whether the level of cannabis use in patients with schizophrenia modulates the level of thought disorder via a modulation of the functional connectivity between the temporal lobe and the Putamen. Analyses will be controlled for the composition of cannabis, in particular the tetrahydrocannabinol / cannabidiol ratio.

Bromocriptine for Patients With Schizophrenia and Impaired Glucose Tolerance
SchizophreniaGlucose IntoleranceThis is a multicenter open-label, pilot study to evaluate the safety and tolerability of bromocriptine, a dopamine D2/D3 receptor and serotonin 5-HT2C receptor agonist, as an adjunct to preexisting standard-of-care antipsychotic drug (APD) regimens in the management of APD-associated impaired glucose tolerance (IGT)/insulin resistance (IR). The ultimate aim of the study team is to evaluate the efficacy of bromocriptine in treating the metabolic disturbances associated with APDs and the hypothesis is that bromocriptine will be a well-tolerated, safe, and inexpensive way to ameliorate these metabolic complications and prevent or delay the onset of type 2 diabetes (T2D). This study will be a small, short-duration pilot focusing on safety and tolerability. Twenty psychiatrically stable APD-treated outpatients, at two sites (VA Pittsburgh and Stanford), aged 18 to 60 years old, with schizophrenia and comorbid IGT will be recruited and receive 6 weeks of bromocriptine (flexibly titrated, 2.5-5.0 mg PO daily). Key inclusion criteria are: 1) currently being treated with second generation APDs for 3 or more months with no change in dose in the 1 month prior to enrollment, 2) fasting glucose 100 to 125mg/dL and/or hemoglobin A1c (HbA1c) 5.7-6.4%. Key exclusions are: 1) prior APD nonadherence, 2) drug/alcohol abuse in the 3 months prior to screening, 3) a history of violent behavior/psychoses, 4) pregnancy, or 5) a diagnosis of diabetes. Subjects on other dopamine agonists or on medications that may interact with bromocriptine and those taking corticosteroids or other medications that may alter glucose levels will be excluded. The purposes of the study are to demonstrate safety/tolerability, demonstrate feasibility, provide proof of concept, and provide an open-label assessment of the metabolic and psychiatric effects of bromocriptine in patients with schizophrenia treated with APDs. The primary metabolic outcome measures will be change in IR as measured by the HOMA-IR and change in IGT measured by HbA1c. Secondary metabolic outcome measures include body weight, fasting lipids, and prolactin. The specific aims are as follows: Specific aim 1: To establish the safety and tolerability of bromocriptine in patients with schizophrenia and IGT/IR treated with APDs. Specific aim 2: To demonstrate feasibility/proof of concept for an improvement in APD-induced IGT/IR with bromocriptine.

Do Antipsychotic Agents Induce Supersensitivity in Humans: A Combined PET/MRI Study in Patients...
SchizophreniaThe aim of the present study is to detect changes in the dopamine system in the brain of patients with schizophrenia, especially when pretreated with antipsychotic medication. Here, the investigators want to find out whether the treatment with these drugs can cause permanent changes in docking points (receptors) of dopamine in the brain. It will be examined whether number and response of dopamine receptors is altered, which are associated with the onset of psychotic symptoms. For this purpose, a single PET/MR measurement will be performed in all participants. In total 140 volunteers, consisting of 30 healthy volunteers, 20 first-episode, drug-naive patients with schizophrenia and 90 pretreated patients with schizophrenia will be included over a time period of three years. In addition, the influence of nicotine consumption on dopamine receptors will be invesitgated by comparing data from smoking and non-smoking patients. In clinical practice, an elevation of dopamine action caused by alterations in receptors in the brain is of most importance. This may be the reason why the treatment with antipsychotic agents does not work in some patients. In addition, a permanent elevation of dopamine action is associated with permanent brain alterations by these drugs. The result can contribute to work out valuable indications, whether it makes sense to continue a long term therapy with antipsychotic drugs in a patient. But also the in-depth understanding of the impact of nicotine on the course of therapy can help to open up possibilities for improved drug treatment.

Early-Phase Schizophrenia: Practice-based Research to Improve Outcomes
First Episode PsychosisThe goal if the project is to develop a learning health network devoted to the treatment of first episode psychosis.

Effect of Nicotine Transdermal Patch on Cognitive Function and Glycolipid Metabolism in Non-smoking...
SchizophreniaSchizophrenia is a group of severe mental disorders of unknown etiology, with significant abnormalities in mental activities such as cognition, thinking, emotion, and behavior, and lead to obvious occupational and social function damage. At present, many studies have found that nicotine and cognitive function changes are related, and many studies have carried out a series of explorations for patients with schizophrenia, but there is no study on the mechanism of nicotine on cognitive function in patients with schizophrenia through changes in glycolipid metabolism, and this study intends to explore whether nicotine participates in the cognitive changes of patients with schizophrenia by regulating glycolipid metabolism, which is conducive to the in-depth study of the mechanism of cognitive function change in schizophrenia, in order to find an effective way to improve the cognitive function of schizophrenia.

Mental Health During the Whole Life Cycle of Community Patients With Schizophrenia
SchizophreniaSchizophrenia is one of the components of severe mental disorders. It has the characteristics of prolonged course, low cure rate, high recurrence rate and high disability rate. It brings many short-term and long-term effects to individuals, families and society. Studies on patients with schizophrenia mainly focus on cross-sectional and case-control studies, but there is a lack of long-term follow-up of patients with schizophrenia in the community. Therefore, this study would establish a cohort study to solve the chronological relationship between exposure and effect, focus on community schizophrenia, and establish a community schizophrenia patient biobank that has been tracked for a long time from diagnosis.