Evaluation of Social Skills Intervention on Cognitive Function in Schizophrenia
SchizophreniaIntervention aimed at improving understanding of irony in social situations by using movies and comic strip will improve theory of mind.
Phenomics and Genomics of Clozapine Pharmacotherapy
Schizophrenia Spectrum and Other Psychotic DisordersA burgeoning body of research has pointed to increased efficacy of clozapine (CLZ) over other antipsychotics in schizophrenia (SCZ). On the other hand, safety concerns likely cause underutilization across a range of European and other nations. The lack of data available to predict efficacy and adverse drug reactions (ADRs) of CLZ further contributes to underprescription rates in these countries. Here, we hypothesize that (epi)genetic and non-genetic factors aid to help predict treatment outcome (efficacy + ADRs) to CLZ. We furthermore posit that such prediction will result in enhanced quality of life of both patients and family members. Our primary objective is to predict CLZ treatment outcome based on phenotypic and genetic data obtained through the current design. The first secondary objective is to investigate which methylation levels/patterns are correlated with CLZ treatment outcome. The second secondary objective is to aid in the further elucidation of the genetic architecture of SCZ and any possible differences between 'regular' SCZ patients and those on CLZ, who are generally more severely ill. We thus intend to cover two currently unmet needs using a precision medicine approach: the lack of knowledge about determinants of treatment response to CLZ and the lack of insight into neurobiological differences between 'regular' SCZ and relatively treatment resistant subjects (CLZ users). The prime analysis will be a common variant hypothesis-generating genotyping endeavor investigating treatment response to CLZ. Additional analyses include whole-genome methylation and gene expression analyses and analyses of non-genetic determinants of response. We will include 2,500 CLZ treated patients for our discovery cohort, which is in line with previous whole-genome pharmacogenomics studies and our power calculations. We will replicate any genome-wide loci using our prospectively collected cohort of new users (N=59). Potential yields include a publicly available prediction tool to help identify patients responsive to CLZ in early disease stages and prevent harmful effects. In addition, common variant analyses compounded by pathway analyses may help elucidate the mechanisms of action of CLZ. We ask for broad informed consent from participants ensuring rich, longitudinal phenotypic and genotypic data resources for both currently planned and future analyses, allowing e.g. next-generation sequencing focused on both CLZ and SCZ disease genetics (e.g. in large consortia). We plan to also generate polygenic risk scores (PRS) of CLZ efficacy and use those to identify other diseases or patients for which CLZ may be helpful, e.g. schizoaffective disorder patients who are sometimes first treated with mood stabilizers. Last, evidence hints that disparaging genetic loci influence efficacy to different antipsychotics. Adding genetic data from our cohort to existing datasets of response to other antipsychotics may help identify such loci. Finally, comparison studies with non-CLZ using patients suffering from SCZ may deepen the understanding of biological mechanisms underlying treatment resistance (or: a relatively severe course of illness).The results of this genetic part of the study will be combined with the results from our other research protocol 'Phenomics and genomic of clozapine pharmacotherapy - New Users'.The overarching goal of both projects is to create a prediction model for clozapine outcome (response (and side effects). This model includes genetic, epigenetic and clinical data.
Therapeutic Drug Monitoring for Individualized Clozapine Therapy
SchizophreniaThe purpose of this study is to evaluate the factors affecting the occurrence of adverse drug reactions (glucose and lipid metabolism abnormality, changes in liver function index and sleeping tendency) and clinical effects in schizophrenia patients with clozapine treatment
Social Isolation and Loneliness in Older People
Very Late Onset SchizophreniaAlthough psychotic disorders such as schizophrenia usually present in late adolescence or early adulthood, research suggests that a substantial subset of people are diagnosed for the first time after the age of 60. This condition is referred to as 'very late-onset schizophrenia-like psychosis' (VLOSLP). People with VLOSLP are thought to experience high levels of social isolation, yet there has been little research systematically examining this. Additionally, little is known about how lonely people with VLOSLP feel, or how this group relate to and perceive other people. This study aims to examine levels of social isolation and loneliness in patients with VLOSLP. The investigators also aim to explore aspects of social cognition in relation to VLOSLP. A case-control study design will be used to examine the relationship between VLOSLP, loneliness, social isolation and social cognition. The case group will be people diagnosed with a non-organic psychotic disorder after age 60. The comparison group will be those aged 60 and above in contact with mental health services for a mental health difficulty, except from a psychotic disorder or dementia.
A German Multicenter Study on Toxoplasma Gondii in First-episode Schizophrenia
SchizophreniaSchizophreniform Disorder1 moreEnvironmental risk factors for the development of schizophrenia include infections during the perinatal period or later in life with Toxoplasma gondii (TG) being one of the candidate agents. A recent review (Torrey and Yolken, 2003) on TG in schizophrenia and other serious mental disorder reported higher antibodies to TG in patients compared to controls in 18 of 19 studies, one having been conducted by the investigators group. In a second, independent study on first-episode schizophrenia (n=56) and control subjects (n=32), sera were sampled and standard instruments used to assess diagnoses and psychopathology, respectively to screening controls. For the total sample, contacts with animals during pregnancy and age emerged as a non-significant predictors of TG IgG titers. Means of patients' and controls' TG IgG titers did not differ significantly but variances did; a subgroup of patients' titers reached much higher levels than those of controls. Patients in the high TG IgG subgroup were older (p=0.001), also they were older when psychiatric symptoms appeared, more individuals had regular animal contacts during pregnancy, or rural upbringing including regular animal contact, more consumption of raw meat, and a higher absolute treatment response (all trend levels). Regarding the short term course of patients, the investigators detected decreasing IgG titers in several individuals A power analysis demonstrated that results fell short of significance due to lack of statistical power. Based on the power analysis, the investigators propose an opel label, multicenter study at three regionally different sites within Germany (Halle, Hamm, Heidelberg). The investigators intent to study 173 first-episode patients with schizophrenia, schizoaffective, and schizophreniform disorder and 173 matched controls. The investigators hypothesize that - according to the heterogeneity of the illness - a subgroup of patients will exhibit higher TG IgG titers compared to the remaining patients and to controls; that this subgroup will have had regular contact with animals during pregnancy and early life as well as developmental delays; and that clinical improvement, response to treatment, and subjective well-being will run parallel with TG IgG decrease. Patients shall be assessed on admission to hospital, at discharge and at 6- and 12-month-follow-up with respect to TG antibody titers, symptomatology, neuropsychology, predictors of outcome, quality of life, and neurological soft signs. In controls two assessments shall be performed, 12 months apart. All foreseen assessments will be performed using standard measurement instruments with sound reliability and validity such as the SCID and the PANSS. Exposure to cats, other warm-blooded life-stock, and raw meat will be assessed using a special questionnaire.
The Quality of Life of Patients With Severe Illnesses
SchizophreniaHIV InfectionsLately researchers and clinicians have emphasized the health related quality of life. Several reasons account for this trend. First of all, the advanced medical practices have contributed to the increased life expectancy. Secondly, the pattern of diseases has shifted from high acuity to chronicity. Therefore, the effectiveness of health care could not be solely evaluated by the rates of morbidity and mortality. The state of patients' quality of life has become the pivotal indicator of the effectiveness of health care interventions. On the other hand, patients' subjective perceptions of health care are crucial factors in treatment processes. Therefore quality of life becomes reference in choosing health care interventions to enhance the benefits of patients. The scopes of quality of life research include the essence of quality of life, the measurements of quality of life and the relationships between quality of life and its related factors, etc. The local researchers have long put efforts in quality of life research. The results of these studies have contributed to the understandings of different patients' quality of life. However, the majority of studies have focused on specific diseases. This study propose to extend the scope of quality of life research to study patients' quality of life of two severe illnesses, i.e. HIV infections and schizophrenia. These two illnesses represent two severe physical and psychiatric illnesses. Even their etiology, mechanisms, disease process, signs and symptoms, and treatments are different. However, the similarities of these two illnesses include both are severe illnesses without cure, both are stigmatized by the society. Patients with these two illnesses suffer in their personal lives, social relations and quality of life. Therefore the current study to further investigate and compare and contrast the essence of patients' quality of life and their related factors. The proposed study is a second year study of the two-year study - The quality of life of patients with severe illnesses (NSC93-2314-B-002-294). The first year study focused on the investigation of the quality of life of patients with HIV infections (NSC93-2314-B-002-294). The aim of this proposed study is to compare and contrast the quality of life and its related factors of patients with schizophrenia and HIV infections. The contributions of this study include the in-depth understandings of quality of life of patients with HIV infections and schizophrenia and the comparison of quality of life of different illnesses. The results serve as the foundations in future development of intervention programs to enhance patients' quality of life and cost-effectiveness analyses.
Gut Microbiome in AP Naive
Psychotic DisorderSchizophreniaAntipsychotic (AP) medications are currently the cornerstone of treatment for schizophrenia (SCZ), with off-label prescription rapidly increasing in youth, with an established two-fold increase in standardized mortality ratio attributable to cardiovascular disease in this population. However, APs have been associated with common and serious metabolic adverse effects including weight gain and diabetes, to which youth are disproportionally vulnerable. The Gut Microbiome (GMB) has been suggested as a potential target warranting further study as a mechanism of AP induced weight gain and has also been linked directly with cognition and behavior. It is hypothesized that there will be changes in the gut microbiome overtime with treatment correlated with metabolic measures and that APs will produce changes in glucose tolerance, insulin sensitivity, adipokines, glucagon like peptide (GLP)-1, lipids, fasting glucose, body weight, and cognition.
Searching for Early Biomarkers of Long-term Hepatic, Metabolic and Endothelial Dysfunction in Non-affective...
SchizophreniaPsychosis1 moreThis study aims to evaluate, at long-term, the occurrence of liver disease and cardio-vascular risk, in a sample of patients diagnosed with first episode of non-affective psychosis.
Effects of Hyperprolactinemia Induced by Antipsychotic Drugs on Bone Metabolism
SchizophreniaThe study is aimed to assess the severities of hyperprolactinemia caused by antipsychotic drugs and the effects of the duration of hyperprolactinemia on bone metabolism in schizophrenia patients.
Visual Information Processing in Schizophrenia Patients With Visual Hallucinations
SchizophreniaVisual Hallucination2 moreOccurrence of visual hallucinations (VHs) in schizophrenia depend in part on disorders in the processing of late visual information (Top-Down). The broader question of how these top-down mechanisms (cognitive and / or emotional mechanisms) are involved in the occurrence of VHs remains to be specified and very few behavioral studies have so far been interested. The investigators propose to study the implication of Top-Down mechanisms in the visual hallucinatory manifestations, more specifically in the processing of ambiguous stimuli during an emotional priming task. Schizophrenia patients with VHs would have more false visual perceptions in the treatment of ambiguous stimuli than schizophrenia patients with auditory hallucinations or no hallucinations (AH/NH) and healthy controls.