Active clinical trials for "Schizophrenia"

The goal of our research is to check the levels of D-Serine, Glycine, and other Glutamatergic amino acids, in patients with First Psychotic Episode (FPE). These patients are in the early stage of the disease, treated with neuroleptics for short periods of time, and are usually hospitalized for the first time. The hypothesis of the research is that we will find low levels of Glycine and D-Serine in these patients. Following an Anti-psychotic treatment we will expect these levels to return to the norm, and that this correction will be accompanied by a reduction of positive and negative symptoms. In addition, we will check the D-Serine and Glycine levels in the plasma of first degree relatives of the patients and a group of healthy subjects. The results of this study might support the hypothesis that the Glutamatergic system in involved in the pathology of Schizophrenia from it's early stages. In addition, we will check the levels of Oxytocin and Estrogen in the plasma of patients in FPE. Our hypothesis is that we will find low levels of Estrogen and High levels of Oxytocin in this group of patients. The results of the study might support the hypothesis that Estrogen and Oxytocin are involved in the pathology of Schizophrenia from it's early stages.

We are going to investigate the association of multiple genetic polymorphisms with the metabolic side effects in patients with schizophrenia taking clozapine.

Schizophrenia (SCH) is a devastating brain disorder with grave personal, family and social cost. SCH is a complex and heterogeneous (both genetic and clinical) disorder with oligogenetic endowed vulnerability risk of disease, which manifested as a clinical syndrome comprised of positive, negative and cognitive symptoms in late adolescent or young adulthood under the interaction with environmental stress. The fact that most positive psychotic symptoms can be well controlled by dopamine-blocking antipsychotics substantiates that dopamine hyperactivity is the pathophysiological model of SCH positive symptoms. This is the dopamine model of SCH. The presence of negative and cognitive symptoms has not being fully explained by the dopamine model. The hypo-glutaminergic function was hypothesized to replace or to supplement the dopamine pathological model. The hypo-glutaminergic state was due to a neurodevelopmental disturbance in early-stage of life, and was coined as a pathophysiological mechanism of SCH. The neurodevelopmental disturbance supports the hypo-glutamine model based on the cytoarchitecture abnormality in glutamate-pyramidal cells and reduced gray matter volume. We have found potential vulnerability genes of DISC1 and NRG1 in our Taiwanese SCH family samples. These two genes have functions on neurodevelopmental process. Besides, we, the investigators, also found two vulnerability genes of DRD2 receptor gene and COMT genes in our Taiwanese SCH families. The dopamine neurotransmission disturbance could be another pathophysiological mechanism of SCH. With the awareness of confounding variables of antipsychotic treatment response revealed in pharmacogenetic studies, such as drug metabolism related genes and plasma HVA level, we intend to test the etiological genetic hypotheses in antipsychotic treatment response: (1) The group of neurodevelopmental etiology with risk variations in DISC1 and NRG1 genes is of poor treatment response group; (2) The group of pure hyperdopamine etiology with risk variation in DRD2 receptor and COMT genes is of good treatment group. The potential treatment response related biomarkers, which are directly or indirectly induced by the etiological risk genetic variations, will be examined. These potential biomarkers include homovanillic acid (HVA), glutamate, serotonin, cytokines, and signaling proteins, the neurocognitive function, event-related evoked potential, Niacin skin test, and the AKT1 level in the peripheral lymphocytes. After obtained the informed consult, we'll recruit 30 drug-naïve early schizophrenia (first episode or prodromal stage) patients for pre-treatment and post-treatment assessment on treatment response using positive and negative syndrome scale (PANSS), changes in biomarkers (including biochemical, electro-physiological and neuro-cognitive variables), and brain imaging (studies of component Project No.2 of this Integrated Program) of PET, fMRI, MRI, DSI and MRS (please refer to Project No.2) in addition to genotyping on DISC1, NRG1, DRD2 and COMT genes. The treatment agent is the dopamine stabilizing agent (aripiprazole, 15mg/day for 4 weeks) taking the advantage of dopamine activity balancing effect. Besides, we'll recruit 30 normal controls matched with age, gender, and education, who will receive genotyping and evaluations in all biomarker variables, and brain imaging studies. In order to have adequate statistical power in the genetic analysis of 17 SNP variations in 4 vulnerability genes of DISC1, NRG1, DRD2, COMT, we'll recruit 200 more cases of schizophrenia with duration of illness less than 5 years, who have received regular clinical follow up and had good compliance on medication. The treatment response will be evaluated using PANSS. These cases will also receive all biomarker examinations and genotyping studies. For comparison, we'll also recruit 100 normal controls for study. We'll delineate the heterogeneity issue of schizophrenia using genetic variation, neurobiological biomarkers. This study result will be beneficial for understanding pathogenesis of SCH, and for developing better treatment and prevention methods.

Risperidone is a selective monoamine receptor antagonist. It plays an antipsychotic effect by antagonizing 5-HT2 / D2 receptor. As a second-generation antipsychotic drug, risperidone is metabolized to 9-hydroxy Risperidone in the body very quickly. There are individual differences in the pharmacokinetics and pharmacodynamics of risperidone. For example, CYP2D6 genotype can greatly affect the metabolism of risperidone, and provide evidence for adjusting the type and dose of medication to treat Schizophrenia. In this study, we will verify the correlation between the polymorphisms of genes related with risperidone drug metabolites, drug transporters, drug targets and drug metabolism, pharmacodynamics, adverse reactions in Chinese population, providing basis for clinical rational use of risperidone.

As in the general population, there is a gradual and steady increase in life expectancy of patients with schizophrenia. But this increase is at a smaller scale, with a rate of premature death that is still 2 to 3 times higher than that found in the general population. This excessive early mortality is explained by an overrepresentation of suicide deaths, but also a higher prevalence of somatic diseases, mainly cardiovascular. But today there are only very few epidemiological data on the mortality of patients with schizophrenia, including those aged over 60 years. What are the sociodemographic and clinical characteristics (psychiatric and somatic) of these schizophrenic elderly patients? Do they benefit from a somatic follow-up adequate and systematic? What are their levels of social independence and of quality of life? the answers these questions and the description of the offer of geriatric care and of psychiatric care currently provided by different sectors of psychiatry in France is an indispensable prerequisite for any project to improve the quality of life, state of health and mortality of older patients with schizophrenia.

The purpose of this project is to examine potential mechanisms that may underlie early visual and auditory perception as well as visual and auditory affect perception deficits in schizophrenia and the possible connection between these processes. Given that affect perception largely involves visual and/or auditory information processing and likely relies on intact basic visual and/or auditory perceptual mechanisms, the investigators will examine affect perception deficits within the framework of the more basic visual and auditory processes. Specifically, the investigators will examine magnetophysiological correlates of vocal and visual affect discrimination, non-affective face discrimination and voice discrimination, and simple visual and auditory stimulus discrimination, using Magnetoencephalography (MEG), to identify neural mechanisms underlying perceptual deficits, as well as their contribution to affect perception deficits in schizophrenia.

It is hypothesized, that local retinoic acid (RA) homeostasis is functionally involved in the pathophysiology of depression. In a cross-sectional (and partly longitudinal) analysis, serum RA status will be assessed in healthy controls and subjects with Major Depression, Alzheimer's disease, alcoholism and in subjects with schizophrenia.

The perception of music requires coordinated neural activities in distributed multi-functional centers across both hemispheres. The association between musical abilities and other general cognitive functions have been studied in several populations with inconsistent results. Schizophrenia is a major mental disorder that is strongly associated with cognitive deficits. These often appear before the onset of psychotic symptoms and persist throughout effective treatment of positive and negative symptoms. Like other disorders of psychosis, schizophrenia features general deficits in auditory memory and sensory processing. Recently, Sawada et al. (2014) and Wen et al. (2014) studied music abilities in Japanese and Chinese schizophrenic populations. They both used a standardized assessment for amusia called Montreal Battery of Evaluation of Amusia (MBEA) and found marked impairments in perception of scale, contour, interval, rhythm, meter and memory. Both studies showed that deficits in music perception were associated with cognitive deficits and negative symptoms. In regards to positive symptoms, Wen et al., but not Sawada et al., found a significant association. The present clinical study will assess musical abilities using the MBEA in a Canadian population with and without refractory psychosis. It will explore associations between musical deficits, positive and negative psychiatric symptomology and cognition. The patient population will have a diagnosis of schizophrenia, schizoaffective disorder, affective disorder with psychosis or non substance-related psychosis who were referred to the British Columbia Psychosis Program (BCPP) due to inadequate or no response to at least two trials of antipsychotics. A focus on refractory psychosis may provide greater insights because these patients have relatively more pronounced psychiatric symptoms and cognitive deficits. It will also be valuable to administer the MBEA assessment on a Canadian population, because the test was originally intended for Western populations and its musical phrases were designed with Western tonalities.

The aim of the investigators analysis is to identify the neural correlates of quality of life scores in schizophrenia. For this, the investigators will constitute group of patients according to their quality of life scores and the investigators will analyze their differences in patterns of brain structures and activations.

There were a few studies about the relationship of structural or functional abnormalities of brain and social cognitive dysfunctions in patients with schizophrenia. In addition, default network, which increases activity during mental explorations referenced to oneself including remembering, considering hypothetical social interactions, and thinking about one's own future, may be associated with social cognitive dysfunctions in patients with schizophrenia. Therefore, we will investigate the dysfunction of default network in patients with schizophrenia compared with healthy controls and the effect of default network dysfunctions on the social cognition in patients with schizophrenia.