Manifestations Of Schizophrenia Research Articles

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models.

Schizophrenia is a grave neuropsychiatric disease which frequently onsets between the end of adolescence and the beginning of adulthood. It is characterized by a variety of neuropsychiatric abnormalities which are categorized into positive, negative and cognitive symptoms. Most therapeutical strategies address the positive symptoms by antagonizing D2-dopamine-receptors (DR). However, negative and cognitive symptoms persist and highly impair the life quality of patients due to their disabling effects. Interestingly, hippocampal deviations are a hallmark of schizophrenia and can be observed in early as well as advanced phases of the disease progression. These alterations are commonly accompanied by a rise in neuronal activity. Therefore, hippocampal formation plays an important role in the manifestation of schizophrenia. Furthermore, studies with animal models revealed a link between environmental risk factors and morphological as well as electrophysiological abnormalities in the hippocampus. Here, we review recent findings on structural and functional hippocampal abnormalities in schizophrenic patients and in schizophrenia animal models, and we give an overview on current experimental approaches that especially target the hippocampus. A better understanding of hippocampal aberrations in schizophrenia might clarify their impact on the manifestation and on the outcome of this severe disease.

A Study to Assess the Effectiveness of Planned Teaching Program on Management of Adverse Effects of Antipsychotics in Terms of Knowledge and Attitude among the Staff Nurses working in Govt. Hospital for Mental Health at Gujarat State

Background- Antipsychotics medications are also called ‘neuroleptics or major tranquilizer. They are effective in the treatment of acute and chronic manifestations of schizophrenia and other psychotic conditions Without drug treatment, an estimated 72% of individual who have experienced a psychotic episode relapse within a year. This relapse rate can be reduced to about 23% with continuous medication administration. Aims and Objectives-1. To Assess the Knowledge Regarding Management of Adverse Effects of Antipsychotics before and after implementation of planned teaching program among staff nurses. 2. To Assess the Attitude Regarding Management of Adverse Effects of Antipsychotics before and after implementation of planned teaching program among staff nurses. 3. To find out the correlation between of post test knowledge score and post test attitude score regarding management of adverse effects of antipsychotics among staff nurses. 4. To find out the association between of pre test knowledge score regarding management of adverse effects of antipsychotics among staff nurses with demographic variables. And 5. To find the association between of pre test attitude score regarding management of adverse effects of antipsychotics among staff nurses with demographic variables. Material and Method- Quasi Experimental Research approach used with One Group pre-test and post-test Design. The investigator has used simple random Sampling Techniques for selecting 60 Staff nurses. A Structured Knowledge Questionnaire and Likert’s Attitude Scale were prepared to assess the Knowledge and Attitude of the samples. Result- Mean pre-test knowledge score was 12.62 while Mean post-test knowledge score was 21.55 and the difference was 8.93. The Standard Deviation (SD) of pre-test and post-test knowledge was 2.48 and 2.47 respectively. The calculated ‘t’ value is 29.91which higher than the tabulated ‘t’ value 2.00, which indicates the increased knowledge. Mean Pre-test attitude score was 63.15 while Mean Post-test attitude score was 79.43 and the difference was 16.28. The Standard Deviation (SD) of pre-test and post-test attitude was 4.07 and 3.63 respectively. The calculated ‘t’ value is 26.46 which higher than the tabulated ‘t’ value 2.00, which indicates the increased attitude. The Correlation Coefficient was obtained using Karl Pearson's formula which yielded r=0.155. It suggests Positive Correlation between the Post-test Knowledge Score and Post-test Attitude Score of Samples. Association of selected Demographic Variables with the Pretest Knowledge and Attitude score was computed using Chi Square test and it showed that there is no Significant association between them. Data demonstrated that there was significant increase in the Knowledge and Attitude on Management of adverse effects of antipsychotics after Implementation of Planned Teaching Programme. Hence it is proved that Planned Teaching Programme on Management of adverse effects of antipsychotics was effective in improving knowledge and attitude among Staff nurses working in govt. Hospital for Mental health at Gujarat state.

Partial ablation of frontal cortical subplate leads to developmental abnormalities in KCC2 in the prefrontal cortex

During early brain development, the subplate relays thalamocortical afferents to the overlying cortex. Disconnection of thalamic inputs to the prefrontal cortex by lesions of the subplate of the developing prefrontal cortex at early neonatal periods result in adult-onset behavioral abnormalities reminiscent of positive, negative, and cognitive symptoms of schizophrenia. Delayed maturation of γ-amino butyric acid (GABA) function may contribute to certain abnormalities of the prefrontal cortex and clinical manifestations of schizophrenia. Lesions to the subplate have also been implicated in developmental abnormalities of GABA neurotransmission in somatosensory and visual cortices. Therefore, we sought to examine the effects of subplate lesions in the developing prefrontal cortex of rats on the expression of GABA markers [parvalbumin and glutamic acid decarboxylase (GAD67)] and proteins responsible for GABAergic synaptic maturation [potassium-chloride cotransporter (KCC2) and sodium‑potassium-chloride cotransporter (NKCC1)]. Lesioned and control rats were sacrificed between postnatal days (P) 5 and 90 and immunolabeled for parvalbumin, GAD67, KCC2, and NKCC1 in the prelimbic area of the prefrontal cortex. We found decreased immunoreactivity of KCC2 on neuronal cell membranes at P11 compared to control rats. However, the overall immunoreactivity of KCC2 and NKCC1 did not differ between lesion and control animals at all time points studied. Lesioned rats also showed decreased expression of parvalbumin, but not GAD67. Our results indicate that mechanisms underlying trafficking and membrane binding of KCC2 may contribute to altered GABA receptor function during development in schizophrenia.

Imputed expression of schizophrenia-associated genes and cognitive measures in patients with schizophrenia.

BackgroundCognitive dysfunction is a core manifestation of schizophrenia and one of the best predictors of long‐term disability. Genes increasing risk for schizophrenia may partly act through the modulation of cognition.MethodsWe imputed the expression of 130 genes recently prioritized for association with schizophrenia, using PsychENCODE variant weights and genotypes of patients with schizophrenia in CATIE. Processing speed, reasoning, verbal memory, working memory, vigilance, and a composite cognitive score were used as phenotypes. We performed linear regression models for each cognitive measure and gene expression score, adjusting for age, years of education, antipsychotic treatment, years since the first antipsychotic treatment and population principal components.ResultsWe included 425 patients and expression scores of 91 genes (others had no heritable expression; Bonferroni corrected alpha = 5.49e‐4). No gene expression score was associated with cognitive measures, though ENOX1 expression was very close to the threshold for verbal memory (p = 6e‐4) and processing speed (p = 7e‐4). Other genes were nominally associated with multiple phenotypes (MAN2A1 and PCGF3).ConclusionA better understanding of the mechanisms mediating cognitive dysfunction in schizophrenia may help in the definition of disease prognosis and in the identification of new treatments, as the treatment of cognitive impairment remains an unmet therapeutic need.

Molecular-genetic and immunological aspects of the formation of psychopathological symptoms in schizophrenia

The authors present the data indicating that the formation of psychopathological symptoms of schizophrenia is due to complex and diverse genetic factors associated with various functional and metabolic pathways at different stages of ontogenesis. Despite the fact that at present the genetic basis of positive and negative symptoms as the main pathophysiological manifestations of schizophrenia remains largely unknown, the current level of research allows the identification of some common and unique associations for positive and negative disorders. Based on the analysis of the literature, the specificity of the association of genetic variants with negative symptoms of schizophrenia is shown. It has been also suggested that genes of the immune system may be specifically associated with negative symptoms of schizophrenia. The relevance of studying the relationship of immune system genes, in particular, pro- and anti-inflammatory cytokines, with dimensional characteristics of negative symptoms (abulia-apathy and expressive deficit) is substantiated. Studies of this type have not yet been conducted, despite accumulating data indicating that the heterogeneity of negative symptoms is based on different neurobiological mechanisms. It is concluded that the immunological and molecular genetic study of the subdomains of psychopathological symptoms can be promising as part of the transition to deep phenotyping, which seems to be especially relevant for the study of such an extremely heterogeneous disease from a clinical point of view as schizophrenia. The development of this area is important for solving the problems of precision medicine, which aims to provide the most effective therapy for a particular patient by stratifying the disease into subclasses, taking into account their biological basis.

Contribution of astrocytes to familial risk and clinical manifestation of schizophrenia.

Previous studies have implicated several brain cell types in schizophrenia (SCZ), but the genetic impact of astrocytes is unknown. Considering their high complexity in humans, astrocytes are likely key determinants of neurodevelopmental diseases, such as SCZ. Human induced pluripotent stem cell (hiPSC)‐derived astrocytes differentiated from five monozygotic twin pairs discordant for SCZ and five healthy subjects were studied for alterations related to high genetic risk and clinical manifestation of SCZ in astrocyte transcriptomics, neuron‐astrocyte co‐cultures, and in humanized mice. We found gene expression and signaling pathway alterations related to synaptic dysfunction, inflammation, and extracellular matrix components in SCZ astrocytes, and demyelination in SCZ astrocyte transplanted mice. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co‐twins and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Differentially expressed transcriptomes and signaling pathways related to synaptic functions, inflammation, and especially collagen and glycoprotein 6 pathways indicate abnormal extracellular matrix composition in the brain as one of the key characteristics in the etiology of SCZ.

Association of Cognitive Impairment With Anhedonia in Patients With Schizophrenia.

Anhedonia is considered as one of the five dimensions of negative symptoms and mainly refers to the reduction of the capacity of feeling pleasure. Increasing evidence suggests that anhedonia in schizophrenia may be partly explained by cognitive impairment. However, the associations between specific cognitive impairment and anhedonia are not fully investigated. The purpose of this study was to examine anticipatory anhedonia, consummatory anhedonia, and their cognitive associations in schizophrenia. A total number of 100 patients with schizophrenia and 67 healthy volunteers were recruited. The clinical symptoms of schizophrenia were assessed. Anticipatory pleasure, consummatory pleasure, and cognitive functions of each participant were measured. Multiple linear regression analysis was performed to investigate the influencing factors of anhedonia in schizophrenia. The results showed no significant differences in sex, age, education year, body mass index (BMI), and marital status between the schizophrenia group and healthy control group (all P > 0.05). Both anticipatory and consummatory pleasure in the schizophrenia group were significantly lower than those in the healthy control group (all P < 0.05). Immediate memory, visual spanning, language, attention, and delayed memory were significantly poorer in the schizophrenia group (all P < 0.05). The results showed that language deficit is an independent risk factor for anticipatory anhedonia (B' = 0.265, P = 0.008, 95% CI: 0.038-0.244), while delayed memory deficit is an independent risk factor for consummatory anhedonia (B' = 0.391, P < 0.001, 95% CI:0.085-0.237). To the best of our knowledge, this is the first study that reported the specific cognitive associations of anhedonia in schizophrenia. The findings have added new evidence on the influencing factors of anhedonia and provided clues for the associations between clinical manifestations of schizophrenia.

The incidence of depressive disorders in patients with schizophrenia

Summary. Introduction. Historically, depressive disorders have been described in various forms of schizophrenia by Kraepelin (1923) or as a reaction to illness by Bleuler (1922). One of the alternative points of view that has been considered in recent years is that depressive disorders are a comorbid condition of schizophrenia or one of the manifestations of schizophrenia. However, to date, depression, as a symptom, is not included in the diagnostic criteria of the ICD-10. Methodological approaches to diagnosing depressive disorders in patients with schizophrenia differ in different countries and research groups. This influences the prevalence rates of depressive disorders in schizophrenic patients. Purpose. The study and systematization of studies of the incidence of depressive disorders in patients with schizophrenia.Methods. Russian-language and foreign literature was analyzed with a search depth of 10 years (2010–2020) in the following databases: PubMed, Springer, Wiley Online Library, Taylor &amp; Francis Online, US National Library of Medicine National Institutes of Health, Science Direct and eLIBRARY .RU.Results. A total of 51 studies of depressive disorders in children and adults with schizophrenia were found.Conclusion. The frequency of occurrence of depressive disorders in patients with schizophrenia varies from 9.1 and to 100%, the average frequency is 41.6%. Their frequency is variable and depends on the region of residence and ethnicity. It is noted that depressive disorders in patients with schizophrenia are more often recorded among residents of the Middle East (72.7%), Russia (61.8%) and Europe (39.6%), less often among residents of Southeast Asia (32%) and the Pacific region ( 37.3%). The countries with the highest incidence of depressive disorders in schizophrenia include: USA, Germany, China; and to the countries with the lowest frequency — Denmark, Israel, South Africa. Also, I would like to note that the largest number of studies conducted was in Europe (16 studies with 36 928 patients with schizophrenia), the USA (6 studies with 2314 patients) and the Russian Federation (6 studies with 582 patients). In general, in the world, according to 51 studies analyzed, the incidence of depressive disorders in schizophrenia in men is higher than in women, although gender differences did not reach statistical significance in all regions of the world.

Изменение некоторых провоспалительных хемокинов, цитокинов и показателей нейродеструкции в крови у пациентов с первым эпизодом шизофрении при терапии антипсихотиками

In a longitudinal prospective experimental study to study some pro-inflammatory chemokines, cytokines and neurodestruction indicators in patients with the first episode of schizophrenia during therapy with first-and second-generation antipsychotics, 40 patients with a diagnosis of F20.09 were examined, of which 20 took haloperidol and 20 risperidone. CCL2, sTREM-1, sTREM-2, TGF-β1, VILIP-1 and sRAGE in the blood serum by flow fluorimetry before the starts of therapy and after 8 weeks were determined. Before treatment, the CCL2 value exceeded the control values by 65%, sTREM-1 – by 120%, VILIP-1 – by 60%, sRAGE – by 79%. After 8 weeks of therapy with haloperidol, the blood levels of CCL2, VILIP-1, TGF-β1 continued to increase and sRAGE decreased. During the treatment with risperidone, an increase in the content of only VILIP-1 was noted, with a decrease in CCL2, TGF-β1 and sRAGE. The results indicate an increase in the central nervous system damage during the manifestation of schizophrenia, while therapy with risperidone in comparison with haloperidol has a beneficial effect on a greater number of the studied parameters.

Traumatization and Schizophrenic Disorders - A Multidimensional View

Prevalence of traumatizing of patients with schizophrenia is higher as in the normal community. Meta analyses show significant relationships between traumatic experiences in childhood and psychotic disorders. Patients with schizophrenia as well as those with posttraumatic stress disorder (PTSD) are characterized by brain morphological changes (mygdala und Hippocampus). In these two patient groups, neuroendocrinological disturbances (cortisol und α-amylase) as well as a worse clinical outcome could be additionally found. In the psychodynamic theoretical discussion, there are only few approaches concerning trauma and psychosis. Specifically here, the name of Frieda Fromm-Reichmann should be noted, who already pointed out the great meaning of child traumatization (especially physical and sexual abuse) for the later manifestation of schizophrenia. She also developed first principles of analytic psychosis therapy with the working on the deep life anxiety caused by the trauma in the here and now of the transference situation. It is assumed that schizophrenic disorders and PTSD have to be understood as trauma consequence diseases, which occur in comorbidty in a so far unknown extent.

Combined Low Dose of Ketamine and Social Isolation: A Possible Model of Induced Chronic Schizophrenia-Like Symptoms in Male Albino Rats.

While animal models for schizophrenia, ranging from pharmacological models to lesions and genetic models, are available, they usually mimic only the positive symptoms of this disorder. Identifying a feasible model of chronic schizophrenia would be valuable for studying the possible underlying mechanism and to investigate emerging treatments. Our hypothesis starts from the observation that combining ketamine with isolation could result in long-lasting neuro-psychological deficits and schizophrenia-like features; thus, it could probably be used as the first model of chronic schizophrenia that emphasizes the characteristic of having a multifactorial etiology. By the means of this study, we investigated the effects of ketamine administration combined with isolation in inducing schizophrenia-like symptoms in male albino rats and the brain reactive oxygen species levels. Our results showed that the number of lines crossings in the open field test, the number of open arm entries in the elevated plus maze, and the spontaneous alternations percentage in the Y-maze were significantly lower in the ketamine + isolation group compared to both the control and ketamine + social housing group (p < 0.05). Furthermore, the ketamine + isolation intervention significantly increased the MDA levels and decreased the GPx levels both in the hippocampus and the cortex of the rats. In addition, our premise of creating a model capable of exhibiting both positive and negative symptoms of schizophrenia was also based on adding the aripiprazole treatment to a group of rats. Therefore, we compared the ketamine + social isolation group with the ketamine + social isolation + aripiprazole group in order to attempt to discover if the antipsychotic drug would significantly decrease the potential positive schizophrenia-like symptoms induced by social isolation and ketamine. Given that we obtained significant results, we cautiously presume that this might be an important step in developing our animal model capable of illustrating both positive and negative symptoms of schizophrenia. This study could be a first step towards the creation of a complex animal model capable of exhibiting the multifactorial origin and manifestation of schizophrenia.

Cognitive symptoms associated with antipsychotic course experience in residual schizophrenia

Urgency. The cognitive symptoms of schizophrenia are recognized either as a part of a negative complex of symptomatic, where cognitive malfunction seem to be the secondary complication of emotional and motivational dysregulation; or as a separate group of schizophrenia manifestations that constitutes a massive part of a residual condition. Aim – to evaluate the cognitive functioning and analyze its violation levels in association with antipsychotic course experience in patients with residual schizophrenia. Results. The assessment of cognitive functions was established by direct testing in clinical setting. Education in years varied from 9 to 16, mean 11,27±2,12 in the population under study. The basic level of cognitive impairment was established: verbal memory test result was 31,6±11,6; digit sequencing test result was 13,4±5,7; token motor task test result was 40,1±18,3; verbal fluency test result was 41,2±10,7; symbol coding test result was 30,6±13,1; tower of london test result was 12,2±4,5. Some correlations were found: for chlorpromazine we can assume minor negative impact on token motor task (r= -0,22) and verbal fluency test (r= -0,27) results; for haloperidol we can assume more pronounced but still minor impact on token motor task (r= -0,22), verbal fluency test (r= -0,27), verbal memory test (r= -0,28) and tower of London test (r= -0,20) results; for trifluoperazine we can see minor negative impact on verbal fluency test (r= -0,26); for clozapine we can’t find any representative correlations with cognitive tests; chlorprothixene as we can assume have minor negative impact on verbal memory test (r= -0,32) result, but minor positive – on tower of London test (r= 0,21) result; for risperidone also assume minor positive impact on sequence coding test (r= 0,25), but other tests in battery show no significant correlations; for zuclopenthixol we can assume minor negative impact on token motor task (r= -0,22) and verbal fluency test (r= -0,31) results.

Mental Disorders Associated with the Abuse of Synthetic Cannabinoids (Spices)

Introduction: the abuse of synthetic cannabinoids may trigger the development of mental disorders characterized by distortions of disease processes that can cause incorrect diagnosis.Objective: to study the phenomenon of the abuse of synthetic cannabinoids (Spice) as a trigger psychotic episode in psychiatric patients (with schizophrenia and personality disorders) and risk factors for developing paranoid schizophrenia.Patients and research methods: 291 men were examined: 241 with dependence on synthetic cannabinoids — 101 of them were diagnosed with personality and behavior disorders in adulthood, 140 with a diagnosis of paranoid schizophrenia and 50 with a diagnosis of paranoid schizophrenia without drug dependence.Research methods: clinicalpsychopathological, psychometric (SANS, CGI, MMPI), follow-up, statistical R (R version 3.2.4).Results: intoxication conditions caused by synthetic cannabinoids can provoke the development of psychotic episodes and be a trigger for the manifestation of schizophrenia. There are four variants of narcotic intoxication: delirious, schizophrenic, with pseudo-hallucinations, with delirium. The personalities of patients addicted to synthetic cannabinoids are similar in the prevalence of emotionally unstable, rigid, introverted, deviant traits. Patients with personality disorders, dependent on synthetic cannabinoids, differed from typical drug addicts in such patterns of behavior as disorganization, conflict, unpredictability, spontaneity, thoughtlessness of actions, impulsivity, and nonconformity. The stigmatizing signs of the schizophrenic process in patients who are dependent on synthetic cannabinoids are the symptoms of abulia–apathy of mild severity. Patients with schizophrenia, dependent on synthetic cannabinoids, differed from patients without dependence on drugs by the phenomenon of the absence of an emotional defect expressed in the expressiveness of emotions, the desire for communication.Conclusion: the phenomenon of synthetic cannabinoid abuse is a trigger of a psychotic episode in both schizophrenic patients and those with personality disorders in whom antisocial, schizoid and paranoid personality traits prevail. The abuse of synthetic cannabinoids is a risk factor for the development of paranoid schizophrenia, which differs from schizophrenia without drug dependence by a mild degree of stigmatizing symptoms of abulia–apathy and social activity during periods of short-term remissions.

Pecularities of mental pathology at psychiatric patient with the comorbid somatic disorders

The paper presents the results of a comprehensive clinical and psychopathological examination of patients with schizophrenia comorbid with somatic pathology. The etiological factors and preconditions for the formation of schizophrenia combined with somatic pathology, general clinical and dynamic characteristics, and features of mental disorders, severity and specificity of clinical and psychopathological manifestations of schizophrenia are analyzed. It was found that the combination of schizophrenia with somatic diseases is more "malignant" variants of the course of psychotic disorders, including an increase in the number of hospitalizations, earlier manifestation, significant increase duration and greater severity of psychopathological symptoms.&#x0D; The specificity of mental disorders in patients with schizophrenia with somatic disorders was manifested by a predominance of disorders of sensation and perception in the form of senestopathy (schizophrenia with CVD and F 20 with obesity), hyperesthesia (schizophrenia with diabetes 2) and complex hallucinations.&#x0D; An important characteristic of mental disorders in patients with schizophrenia with somatic pathology is the presence of emotional disorders in the form of rigidity (in schizophrenia with CVD and obesity) and explosiveness (in schizophrenia with diabetes 2) emotional reactions, as well as depressive and anxiety (schizophrenia with CVD) and dysphoric (in schizophrenia with diabetes 2 and obesity) mood disorders. According to the frequency analysis of clinical-biological and social factors of formation, as well as features of clinical-psychopathological structure of schizophrenia in patients of the examined groups, diagnostic clinical-psychopathological signs (risk markers) of combination of schizophrenia with specific variants of somatic disorders are established.&#x0D; The obtained results show that the combination of schizophrenia with somatic disorders is reflected in the deepening and peculiarities of psychopathological symptoms, reducing the level of social realization of patients and requires the attention of clinicians in developing treatment strategies.

Modeling Schizophrenia with Glioblastoma Cells: In Vitro Analysis of Risperidone Treatment on Glial Spheroids.

Glioblastoma is the most malicious type of glioma presenting a genetic background via diverse mutations and exhibits differential sensitivity to treatment. Meanwhile, schizophrenia is a heterogeneous disease with a complex etiology. Studies report an elevation in pro-inflammatory cytokines in patients with schizophrenia and changes in biochemical metabolism. In the present study, the tumor spheroid technology is applied to two different glioblastoma lines which resemble schizophrenia manifestation along with the investigation of the potential anti-tumor effect of an atypical antipsychotic drug, risperidone. Our hypothesis built on case reports showing patients with schizophrenia being treated with risperidone that turned out to have glioblastoma in post-mortem evaluation. Risperidone has been suggested to carry therapeutic effects for glioblastoma and elongated lifespan after the diagnosis of cancer. In this current study, 3D models using C6 and U87 glioblastoma cells and monocytes for representing the disease grown as multicellular spheroids were established. Spheroids were treated with the anti-schizophrenic agent risperidone and indicated almost similar results to the clinics suggesting that glioblastoma and schizophrenia share mutual physiological characteristics. U87 and C6 spheroid systems were analyzed molecularly after the treatment of risperidone where U87 spheroid models were found highly resembling the overall behavior of schizophrenia. This present work correlated the stated two diseases in molecular level to encourage the efforts for personalized medicine. The anti-tumor effects of risperidone on glioblastoma is not very well established yet. It should not be missed that a picture of schizophrenia in clinics may be the result of an underlying lesion in a specific brain area. Thus, especially schizophrenia patients who may be at risk for developing brain tumors should be further investigated and treated accordingly.

Association of the kynurenine pathway metabolites with clinical, cognitive features and IL-1β levels in patients with schizophrenia spectrum disorder and their siblings

ObjectiveThere is evidence suggesting that tryptophan (TRP)-kynurenine (KYN) pathway dysregulation is involved in the pathophysiology of schizophrenia and is regulated by inflammatory cytokines. The study investigate for the first time whether this dysregulation occurs in advanced stages of the disease as a byproduct or emerges as one of the early and inherited manifestations of schizophrenia. MethodSera of 148 patients with schizophrenia spectrum disorders (SCZ), 139 unaffected siblings (SIB) and 210 controls were investigated. Serum interleukin (IL)-1β levels were measured by ELISA, and TRP, KYN and kynurenic acid (KYNA) levels were measured by a high-performance liquid chromatography system. Also, we collected clinical data by applying Comprehensive Assessment of Symptoms and History in SCZ, and SIS-R in SIB and control groups. ResultsCompared to controls, SCZ and SIB groups had lower TRP and higher KYNA levels. TRP levels showed significant differences only between SCZ and controls (p < 0.01). KYNA levels of both SCZ (p ≤ 0.001) and SIB (p < 0.05) were higher than controls. No statistical significance was found for KYN levels across groups. SCZ and SIB groups had higher serum IL-1β levels than controls (p ≤ 0.001). ConclusionsPatients with SCZ and their siblings exhibited similar clinical features and TRP metabolite levels suggesting that TRP-KYN dysregulation may be an inherited component of the disease putatively conferring increased risk to schizophrenia. Elevation of IL-1β is one of the factors promoting overconsumption of the TRP-KYN pathway leading to increased production of neuroregulatory KYNA and presumably to neurodegeneration.

The Association between Lifestyle Choices and Schizophrenia Symptoms.

Due to poor eating habits, insufficient physical activity, and nicotine use, schizophrenia patients are at increased risk of lifestyle diseases. Factors contributing to unhealthy behaviors include lower socioeconomic status and level of education as well as social isolation. Schizophrenia manifestations such as amotivation, apathy, and cognitive deficits can further hinder development of proper health habits. The aim of this study was to assess the possible association between lifestyle-related choices and schizophrenia symptoms severity. This observational study enrolled 106 patients with schizophrenia (42 Males/64 Females), 18–69 years (mean: 41.89 ± 9.7 years). Mean duration of schizophrenia was 14.61 ± 9.7 years. Multiple significant correlations were found between patients’ lifestyle and their biochemical laboratory parameters (lipid profile and fasting glucose). Most importantly, a significant link emerged between presented habits and schizophrenia symptom severity. There were also significant gender differences in the intake of sweets and sweet beverages. Quite unexpectedly, a behavioral shift towards more healthy lifestyle choices was observed after completion of questionnaires on lifestyle and health habits. There are clear benefits to systematic provision of educational interventions concerning physical activity and proper eating habits to schizophrenia patients. These simple preventive measures could significantly improve both mental and physical health outcomes in schizophrenia patient populations.

Oxidative Stress-Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives.

Schizophrenia is recognized to be a highly heterogeneous disease at various levels, from genetics to clinical manifestations and treatment sensitivity. This heterogeneity is also reflected in the variety of oxidative stress-related mechanisms contributing to the phenotypic realization and manifestation of schizophrenia. At the molecular level, these mechanisms are supposed to include genetic causes that increase the susceptibility of individuals to oxidative stress and lead to gene expression dysregulation caused by abnormal regulation of redox-sensitive transcriptional factors, noncoding RNAs, and epigenetic mechanisms favored by environmental insults. These changes form the basis of the prooxidant state and lead to altered redox signaling related to glutathione deficiency and impaired expression and function of redox-sensitive transcriptional factors (Nrf2, NF-κB, FoxO, etc.). At the cellular level, these changes lead to mitochondrial dysfunction and metabolic abnormalities that contribute to aberrant neuronal development, abnormal myelination, neurotransmitter anomalies, and dysfunction of parvalbumin-positive interneurons. Immune dysfunction also contributes to redox imbalance. At the whole-organism level, all these mechanisms ultimately contribute to the manifestation and development of schizophrenia. In this review, we consider oxidative stress-related mechanisms and new treatment perspectives associated with the correction of redox imbalance in schizophrenia. We suggest that not only antioxidants but also redox-regulated transcription factor-targeting drugs (including Nrf2 and FoxO activators or NF-κB inhibitors) have great promise in schizophrenia. But it is necessary to develop the stratification criteria of schizophrenia patients based on oxidative stress-related markers for the administration of redox-correcting treatment.

Psychosis - A Disconnection from Reality

Psychosis includes loss of contact with reality and may have hallucinations and delusions. It is a side effect of schizophrenia and bipolar issue; however, there are numerous different causes. Psychosis influences how an individual thinks and their perceptions. Their senses might appear to identify things that don't exist, and they might think that it is hard to figure out what is genuine and valid. Individuals with psychosis may hear voices and see individuals or things that are not there, smell odours that others can't recognize. They believe that they are in a critical scenario or somebody is chasing them. An individual may not know that they have psychosis because they dreams feel genuine to them. Psychosis can be overpowering and confounding. At times, the manifestations can make the individuals damage themselves. In rare cases, they might hurt someone else. Psychosis is one of the vital manifestations of schizophrenia.

Preliminary evidence that oxytocin does not improve mentalizing in women with schizophrenia

IntroductionMentalizing, the ability to infer other people's intentions and emotions, is commonly impaired in schizophrenia and may represent an endophenotype. The hypothalamic neuropeptide oxytocin has been shown to improve mentalizing in men with schizophrenia, but its effects in women remain unclear. Given sex differences in the clinical manifestations of schizophrenia and oxytocin system function, this is an important gap to address. MethodsWe tested the effects of a single-dose oxytocin challenge (40 IU) on mentalizing task performance among 26 women with schizophrenia and 38 healthy control women using a randomized, placebo-controlled, double-blind, crossover design. We aimed to replicate our prior study of oxytocin effects on mentalizing in men with schizophrenia, using the same oxytocin administration procedures and performance-based assessments. We used mixed-effects models and equivalence testing as well as Bayesian hierarchical models to examine oxytocin effects. ResultsIn contrast to our previous finding in a male sample, oxytocin did not improve mentalizing in this sample of women with schizophrenia. Exploratory analyses showed that higher anti-dopaminergic medication dosage was associated with a decreased response to oxytocin, consistent with previous findings in men. ConclusionThese findings provide preliminary evidence that exogenous oxytocin administration may have sex-specific effects on mentalizing in schizophrenia. Inclusion of women in future clinical studies with larger samples is critical, as oxytocin effects observed in men may not extend to women with the disorder.