Study of OH Radicals in Human Serum Blood of Healthy Individuals and Those with Pathological Schizophrenia

The human body is constantly under attack from free radicals that occur as part of normal cell metabolism, and by exposure to environmental factors such as UV light, cigarette smoke, environmental pollutants and gamma radiation. The resulting “Reactive Oxygen Species” (ROS) circulate freely in the body with access to all organs and tissues, which can have serious repercussions throughout the body. The body possesses a number of mechanisms both to control the production of ROS and to cope with free radicals in order to limit or repair damage to tissues. Overproduction of ROS or insufficient defense mechanisms leads to a dangerous disbalance in the organism. Thereby several pathomechanisms implicated in over 100 human diseases, e.g., cardiovascular disease, cancer, diabetes mellitus, physiological disease, aging, etc., can be induced. Thus, a detailed investigation on the quantity of oxygen radicals, such as hydroxyl radicals (OH^•) in human serum blood, and its possible correlation with antioxidant therapy effects, is highly topical. The subject of this study was the influence of schizophrenia on the amount of OH^• in human serum blood. The radicals were detected by fluorimetry, using terephthalic acid as a chemical trap. For all experiments the serum blood of healthy people was used as a control group.     

Cystine/Glutamate Antiporter in Schizophrenia: From Molecular Mechanism to Novel Biomarker and Treatment

Glutamate, a crucial excitatory neurotransmitter, plays a major role in the modulation of schizophrenia’s pathogenesis. New drug developments for schizophrenia have been prompted by the hypoglutamatergic hypothesis of schizophrenia. The cystine/glutamate antiporter system x_c⁻ is related to glutamate-release regulation. Patients with schizophrenia were recently discovered to exhibit downregulation of x_c⁻ subunits—the solute carrier (SLC) family 3 member 2 and the SLC family 7 member 11. We searched for relevant studies from 1980, when Bannai and Kitamura first identified the protein subunit system x_c⁻ in lung fibroblasts, with the aim of compiling the biological, functional, and pharmacological characteristics of antiporter x_c⁻, which consists of several subunits. Some of them can significantly stimulate the human brain through the glutamate pathway. Initially, extracellular cysteine activates neuronal x_c⁻, causing glutamate efflux. Next, excitatory amino acid transporters enhance the unidirectional transportation of glutamate and sodium. These two biochemical pathways are also crucial to the production of glutathione, a protective agent for neural and glial cells and astrocytes. Investigation of the expression of system x_c⁻ genes in the peripheral white blood cells of patients with schizophrenia can facilitate better understanding of the mental disorder and future development of novel biomarkers and treatments for schizophrenia. In addition, the findings further support the hypoglutamatergic hypothesis of schizophrenia.     

Intentional inhibition in memory and hallucinations: Directed forgetting and updating.

Hallucinations have been recently associated with inhibitory deficits in memory. In this study, the authors investigated whether hallucinations were related to difficulties to inhibit irrelevant information from episodic memory (Experiment 1) and working memory (Experiment 2). In Experiment 1, a directed forgetting task was used. This task measures participants' ability to intentionally forget some recently learned material, when instructions indicate that it is no longer relevant. In Experiment 2, an updating task was used. This task requires participants to intentionally suppress irrelevant information from working memory. Results showed that patients with schizophrenia with hallucinations presented inhibitory deficits in the directed forgetting task and an increase in the number of intrusions in the updating task, compared to patients without hallucinations and healthy controls. No correlations were found between indices of inhibition and other general, negative or positive symptoms. These findings support the existence of an association between intentional inhibition in memory and hallucinations, and they suggest that problems to suppress memory representations can underlie hallucinations in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychosis as a risk factor for violence to others: A meta-analysis.

The potential association between psychosis and violence to others has long been debated. Past research findings are mixed and appear to depend on numerous potential moderators. As such, the authors conducted a quantitative review (meta-analysis) of research on the association between psychosis and violence. A total of 885 effect sizes (odds ratios) were calculated or estimated from 204 studies on the basis of 166 independent data sets. The central tendency (median) of the effect sizes indicated that psychosis was significantly associated with a 49%–68% increase in the odds of violence. However, there was substantial dispersion among effect sizes. Moderation analyses indicated that the dispersion was attributable in part to methodological factors, such as study design (e.g., community vs. institutional samples), definition and measurement of psychosis (e.g., diagnostic vs. symptom-level measurement, type of symptom), and comparison group (e.g., psychosis compared with externalizing vs. internalizing vs. no mental disorder). The authors discuss these findings in light of potential causal models of the association between psychosis and violence, the role of psychosis in violence risk assessment and management, and recommendations for future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

阿立哌唑治疗精神分裂症的临床评价

目的: 评价国产阿立哌唑对精神分裂症的疗效与安全性。方法: 80例精神分裂症患者随机分为2组:阿立哌唑组40例,给予阿立哌唑10~ 20mg·d^-1,po,qd;氯氮平组40例,给予氯氮平300 ~500 mg·d^-1,po, Bid。采用阳性症状与阴性症状量表(PANSS)评价临床疗效、不良反应症状量表(TESS)评价不良反应,观察8周。结果: 阿立哌唑治疗后PANSS总分减分率为50.4%,有效率为87.5%;氯氮平PANSS总分减分率为49.4%,有效率为85.0%.两组总体疗效相当(P>0.05)。阿立哌唑对阴性症状起效较早。阿立哌唑组常见不良反应有锥体外系反应(EPS)(17.5%)、头痛(12.5%)、恶心呕吐(10%),但与氟氮平组比较差异无显著性(P>0.05),且程度较轻,无血象及糖代谢异常;与氯氮平组较多的过度镇静(37.5%)、流延(45%)、便秘(25%)、体重增加(25%)比较差异有显著性(P<0.05或P<0.01)。结论: 阿立哌唑是一种治疗精神分裂症安全有效的药物。     

Systematic Review and Meta-Analysis of Mass Spectrometry Proteomics Applied to Human Peripheral Fluids to Assess Potential Biomarkers of Schizophrenia

Mass spectrometry (MS)-based techniques can be a powerful tool to identify neuropsychiatric disorder biomarkers, improving prediction and diagnosis ability. Here, we evaluate the efficacy of MS proteomics applied to human peripheral fluids of schizophrenia (SCZ) patients to identify disease biomarkers and relevant networks of biological pathways. Following PRISMA guidelines, a search was performed for studies that used MS proteomics approaches to identify proteomic differences between SCZ patients and healthy control groups (PROSPERO database: CRD42021274183). Nineteen articles fulfilled the inclusion criteria, allowing the identification of 217 differentially expressed proteins. Gene ontology analysis identified lipid metabolism, complement and coagulation cascades, and immune response as the main enriched biological pathways. Meta-analysis results suggest the upregulation of FCN3 and downregulation of APO1, APOA2, APOC1, and APOC3 in SCZ patients. Despite the proven ability of MS proteomics to characterize SCZ, several confounding factors contribute to the heterogeneity of the findings. In the future, we encourage the scientific community to perform studies with more extensive sampling and validation cohorts, integrating omics with bioinformatics tools to provide additional comprehension of differentially expressed proteins. The produced information could harbor potential proteomic biomarkers of SCZ, contributing to individualized prognosis and stratification strategies, besides aiding in the differential diagnosis.     

Temporal discounting of rewards in patients with bipolar disorder and schizophrenia.

Patients with bipolar disorder (BD) and schizophrenia (SZ) often show decision-making deficits in everyday circumstances. A failure to appropriately weigh immediate versus future consequences of choices may contribute to these deficits. We used the delay discounting task in individuals with BD or SZ to investigate their temporal decision making. Twenty-two individuals with BD, 21 individuals with SZ, and 30 healthy individuals completed the delay discounting task along with neuropsychological measures of working memory and cognitive function. Both BD and SZ groups discounted delayed rewards more steeply than did the healthy group even after controlling for current substance use, age, gender, and employment. Hierarchical multiple regression analyses showed that discounting rate was associated with both diagnostic group and working memory or intelligence scores. In each group, working memory or intelligence scores negatively correlated with discounting rate. The results suggest that (a) both BD and SZ groups value smaller, immediate rewards more than larger, delayed rewards compared with the healthy group and (b) working memory or intelligence is related to temporal decision making in individuals with BD or SZ as well as in healthy individuals. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Crosstalk between Schizophrenia and Metabolic Syndrome: The Role of Oxytocinergic Dysfunction

The high prevalence of metabolic syndrome in persons with schizophrenia has spurred investigational efforts to study the mechanism beneath its pathophysiology. Early psychosis dysfunction is present across multiple organ systems. On this account, schizophrenia may be a multisystem disorder in which one organ system is predominantly affected and where other organ systems are also concurrently involved. Growing evidence of the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, such as an association with cognitive dysfunction, altered autonomic nervous system regulation, desynchrony in the resting-state default mode network, and shared genetic liability, suggest that metabolic syndrome and schizophrenia are connected via common pathways that are central to schizophrenia pathogenesis, which may be underpinned by oxytocin system dysfunction. Oxytocin, a hormone that involves in the mechanisms of food intake and metabolic homeostasis, may partly explain this piece of the puzzle in the mechanism underlying this association. Given its prosocial and anorexigenic properties, oxytocin has been administered intranasally to investigate its therapeutic potential in schizophrenia and obesity. Although the pathophysiology and mechanisms of oxytocinergic dysfunction in metabolic syndrome and schizophrenia are both complex and it is still too early to draw a conclusion upon, oxytocinergic dysfunction may yield a new mechanistic insight into schizophrenia pathogenesis and treatment.     

Pursuing the kernel of truth in the psychotherapy of schizophrenia.

This article concerns the utility of pursuing the kernels of truth in the delusions of schizophrenic patients as a means of empathizing with their unique personal experience of events. Pursuing the kernel of truth implies listening for the real interpersonal experiences past and present that are represented within delusions, as opposed to focusing on derivatives of infantile fantasy. This orientation restores the rights of the schizophrenic person as a perceptive observer of events with a valid, although not commonly understood, point of view. A clinical case example is presented in which the delusion of being raped while others stand idly by both literally and metaphorically described a wide variety of interpersonal experiences which had shaped the patient's life. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multimodal Integrative Cognitive Stimulating Group Therapy: Moving Beyond the Reduction of Psychopathology in Schizophrenia.

The authors present a group therapy for schizophrenia called multimodal integrative cognitive stimulating group therapy (MICST). MICST is founded upon a theoretical model that views schizophrenia as a condition characterized by information-processing and memory deficits, which interfere with communication. MICST is designed to stimulate clients' cognitive and memory functioning, improve information processing, and enhance clients' abilities to engage in reality-based conversations. The therapy combines elements of social skills relaxation exercise, cognitive rehabilitation, and traditional psychotherapy but also emphasizes accessing clients' "intact" cognitive functioning by using both visual and auditory modalities. MICST's long-term use, its eager acceptance by clients and staff, and results from various outcome measures support its potential value. However, formal studies are required to more firmly establish MICST's efficacy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)