Difference between treatment-resistant schizophrenia and clozapineresistant schizophrenia

We read the impressive review article“Clozapine resistant schizophrenia:Newer avenues of management”with great enthusiasm and appreciation.The author believes that preventing clozapine resistance from developing may be the most effective treatment strategy for patients with clozapine-resistant schizophrenia(CRS),and optimizing clozapine treatment is a key component.Disentangling the differences between treatment-resistant schizophrenia and CRS is important for studies addressing treatment strategies for these difficult-to-treat populations.

Altered thalamic subregion functional networks in patients with treatment-resistant schizophrenia

BACKGROUND The thalamus plays a key role in filtering information and has extensive interconnectivity with other brain regions.A large body of evidence points to impaired functional connectivity(FC)of the thalamocortical pathway in schizophrenia.However,the functional network of the thalamic subregions has not been investigated in patients with treatment-resistant schizophrenia(TRS).AIM To identify the neural mechanisms underlying TRS,we investigated FC of thalamic sub-regions with cortical networks and voxels,and the associations of this FC with clinical symptoms.We hypothesized that the FC of thalamic subregions with cortical networks and voxels would differ between TRS patients and HCs.METHODS In total,50 patients with TRS and 61 healthy controls(HCs)matched for age,sex,and education underwent resting-state functional magnetic resonance imaging(rs-fMRI)and clinical evaluation.Based on the rs-fMRI data,we conducted a FC analysis between thalamic subregions and cortical functional networks and voxels,and within thalamic subregions and cortical functional networks,in the patients with TRS.A functional parcellation atlas was used to segment the thalamus into nine subregions.Correlations between altered FC and TRS symptoms were explored.RESULTS We found differences in FC within thalamic subregions and cortical functional networks between patients with TRS and HCs.In addition,increased FC was observed between thalamic subregions and the sensorimotor cortex,frontal medial cortex,and lingual gyrus.These abnormalities were associated with the pathophysiology of TRS.CONCLUSION Our findings suggest that disrupted FC within thalamic subregions and cortical functional networks,and within the thalamocortical pathway,has potential as a marker for TRS.Our findings also improve our understanding of the relationship between the thalamocortical pathway and TRS symptoms.

Case Reports: Treatment-Resistant Schizophrenia with Severe Type 2 Diabetes Mellitus Treated with Clozapine

Objective: Clozapine is regarded as the most effective drug for treatment of schizophrenia but has complex adverse effects associated with hyperglycemia and diabetes mellitus. Method: We report that clozapine was very effective to treat positive, negative, and cognitive symptoms and well tolerated to a treatment-resistant schizophrenia patient with severe type 2 diabetes mellitus (DM) under cautious blood-sugar monitoring. Results: Clozapine itself and discontinuation of other psychotropic and anticholinergic agents after switching may improve cognitive function and adherence to the treatment regimens for schizophrenia and DM. Conclusion: Clozapine can be administered to treatment-resistant schizophrenia patients even with severe DM with caution.

Very-high-dose olanzapine for treatment-resistant schizophrenia

Treatment-resistant schizophrenia has an extremely negative impact on mental health and social life. If clozapine, the gold standard treatment, fails, there are very few options left. The literature suggests that high-dose olanzapine (20 - 60 mg/day) is a possible alternative. We report two cases in which very high doses of olanzapine were administered, with significant clinical improvements above 60 mg/day. Clinical, metabolic and cardiac tolerance was good. This report highlights the usefulness of very-high-dose olanzapine in treatment-resistant schizophrenia. The main hypotheses concerning the psychopharmacological mechanisms of very-high-dose olanzapine are discussed.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

What Are the Current and Developing Treatments for Cotard’s Syndrome, Alice in Wonderland Syndrome, and Catatonic Schizophrenia?

Purpose: Cotard’s syndrome, Alice in Wonderland Syndrome, and Catatonia are all rare psychiatric disorders that have relatively little research regarding their treatments. The aim of this article is to highlight any gaps in knowledge regarding represented demographics in these treatment studies, and to discuss the current and upcoming treatment options. Background: This literature review explores under-researched psychiatric conditions: Cotard’s syndrome, Alice in Wonderland syndrome, and Catatonic Schizophrenia. Understanding psychiatric disorders requires basic knowledge of brain anatomy. These conditions are often result of or associated with neurological issues, such as migraines or tumors. The brain has eight lobes, two of four kinds: frontal, parietal, occipital, and temporal lobes, which all govern different functions and abilities. Frontal lobes control judgment, decision-making, personality traits, and fine motor movements. Parietal lobes interpret pain and temperature, occipital lobes handle visual stimuli, and temporal lobes enable hearing. The pre-frontal cortex is associated with high intelligence, psychotic traits, and psychosis. The Broca’s Area in the frontal lobes controls expressive language. These areas and divisions of the brain contribute to the complexity of the psychiatric disorders discussed in this review. Introduction: Cotard’s syndrome is a psychiatric disorder characterized by delusions of being dead or not having certain limbs or organs. It is believed that there is a disconnect between their fusiform face area and the amygdala, causing a lack of familiarity between one’s mind and body. Alice in Wonderland Syndrome (AIWS) is another psychiatric disorder which is characterized by visual hallucinations, such as distorted perceptions of color, size, distance, and speed. The most common symptoms include micropsia and macropsia. Catatonia/Catatonic Schizophrenia is an uncommon type of schizophrenia. This type of schizophrenia is characterized by motor rigidity, verbal rigidity, the flat effect, psychomotor retardation, waxy flexibility, and overall negative symptoms. Thus, these people may come off as emotionally detached, and able to stay frozen in odd positions for periods on end. Treatments and Results: Cotard’s syndrome seemed to be most effectively treated by ECT (electroconvulsive therapy). Alice in Wonderland Syndrome (AIWS) had the highest positive responses to treatment by Valproate (an anti-epileptic drug), as well as intervention to treat the associated neurological conditions they had. Catatonia/Catatonic Schizophrenia seemed to be most effectively treated with a combination of benzodiazepines and ECT. Discussion and Demographics: In all 3 disorders, the Latino and African communities were underrepresented. There also seemed to be an underrepresentation of men in Cotard’s syndrome, and of women in Alice in Wonderland Syndrome. Japan and India seemed to have the highest density of treatment studies in all 3 disorders.

Costs of Schizophrenia at Psychiatric Hospital of Bingerville (Ivory Coast)

Schizophrenia is classified as a priority mental disorder by the World Health Organization (WHO) and accounts for around 35% of diagnoses at the Bingerville Psychiatric Hospital (HPB). The aims of the study were to identify the cost drivers for hospitalization and to calculate the costs of managing schizophrenia in hospital, with a view to planning household expenditure on care. This pilot cross-sectional study involved 31 patients with schizophrenia who had been hospitalized in the various third-category wards at the HPB between 1st January 2019 and 31st May 2020. Sampling was accidental. The methods used to estimate costs were based on the actual costs of drugs, hospitalization and additional examinations which prices were known, and on patients’ estimations for certain expenses such as food and transport. Results: The sex ratio was 3.42, the mean age was 29.52 years. The mean length of stay was 46.19 days, and the most frequent clinical forms were paranoid schizophrenia (41.9%) and schizoaffective disorder (29%). The combination of haloperidol and chlorpromazine was the most common medications for initial treatment (67.8%) and maintenance treatment (41.9%). The average cost of hospitalization at HPB for schizophrenia was XOF 164,412 (€249.90). The average direct medical cost was XOF 105,412 (€160.226) and the average direct non-medical cost was XOF 59,000 (€89.68). The average daily cost of antipsychotic treatment was XOF 795/day (€1.2084). The high cost of drugs as a proportion of hospitalization costs suggested the need of a reflection on the simplification of prescribing practices, assistance in psychiatric emergencies and the development of other alternatives to psychiatric hospitalization in Côte d’Ivoire.

MicroRNAs as potential biomarkers for diagnosis of schizophrenia and influence of antipsychotic treatment

Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.

Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine‑resistant treatment‑refractory schizophrenia:a 12‑week randomized,double‑blind,placebo‑controlled trial

Background:Although clozapine is an effective option for treatment-resistant schizophrenia(TRS),there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine.The main purpose of this randomized,double-blind,placebocontrolled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia(CTRS)patients.Methods:A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride(amisulpride group)or clozapine plus placebo(placebo group).Positive and Negative Syndrome Scale(PANSS),Scale for the Assessment of Negative Symptoms(SANS),Clinical Global Impression(CGI)scale scores,Repeatable Battery for the Assessment of Neuropsychological Status(RBANS),Treatment Emergent Symptom Scale(TESS),laboratory measurements,and electrocardiograms(ECG)were performed at baseline,week 6,and week 12.Results:Compared with the placebo group,amisulpride group had a lower PANSS total score,positive subscore,and general psychopathology subscore at week 6 and week 12(PBonferroni<0.01).Furthermore,compared with the placebo group,the amisulpride group showed an improved RBANS language score at week 12(PBonferroni<0.001).Amisulpride group had a higher treatment response rate(P=0.04),lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group(PBonferroni<0.05).There were no differences between the groups in body mass index(BMI),corrected QT(QTc)intervals,and laboratory measurements.This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients.

Prevalence and Characteristics of Treatment-Resistant Hypertension among Hypertensive Japanese Outpatients

Aims: To retrospectively investigate the prevalence and characteristics of treatment-resistant hypertension (R-HT) among consecutive hypertensive outpatients, since patients with R-HT are candidates for catheter-based renal sympathetic denervation (RD). Methods: Consecutive hypertensive outpatients (n = 999) were recruited in our hospital. R-HT patients who were candidates for RD had clinic systolic blood pressure > 160 mmHg despite taking three or more antihypertensive drugs including at least one diuretics at higher than standard doses. Results: Our survey indicated that only 26 patients (2.6%) were potential candidates for renal denervation. Candidates for RD showed a significantly higher age (P < 0.005), brain natriuretic peptide level (P = 0.0001), urinary albumin/creatinine excretion ratio in spot urine (P < 0.005), pulse wave velocity (P < 0.01), left ventricular end-diastolic diameter (P < 0.005), and interventricular septal thickness (P < 0.005) than the other 973 patients. Candidates for denervation had a significantly lower hemoglobin (P = 0.0001), serum albumin (P < 0.001), eGFR (P < 0.0005), plasma renin activity (P = 0.0001), and plasma aldosterone level (P < 0.005) than other patients, while their urinary sodium/creatinine ratio was higher, indicating that patients with R-HT appeared to have a high salt intake. Conclusion: Our retrospective clinical survey indicated that only 0.5% of Japanese hypertensive outpatients (5/999 patients) were candidates for RD. Therefore, establishment of hypertension cohort network will be essential to recruit R-HT patients for RD.

Genetic variables of the glutamatergic system associated with treatment-resistant depression:A review of the literature

Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide.Up to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,can be defined as treatment-resistant depression(TRD).The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment.Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD.Specifically,the N-methyl-D-aspartic acid receptor(NMDAR)andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR),which are targeted by ketamine and esketamine,are proposed as promising pathways.A literature search was performed to identify studies on the genetics of the glutamatergic system in depression,focused on variables related to NMDARs and AMPARs.Our review highlights GRIN2B,which encodes the NR2B subunit of NMDAR,as a candidate gene in the pathogenesis of TRD.In addition,several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation.These genes encoding glutamatergic receptors could,therefore,be candidate genes for understanding the etiopathogenesis of TRD,as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.

A Qualitative Study on What It Means for Patients with Schizophrenia Living in the Community to Remain on Medication

Background: Little is known about what the experience of “taking antipsychotics” means in a patient’s life. Therefore, this study aims to identify what it means for patients with schizophrenia living in the community to remain on medication. Methods: The participants were five residents of communities, who had been discharged from a psychiatric hospital, but were currently visiting a private psychiatric hospital. In this study, we used participants’ narratives as data and analyzed them according to the procedures described in “An Application of Phenomenological Method in Psychology” (Giorgi, 1975), and “Practice of analyzing materials describing experiences” (Giorgi, 2004). Results: The study results are as follows. 1) The drug may be effective, but Subject (below, S) still wants to take it as little as possible. Meanwhile, S has people who care about S and a person who S can rely on nearby, to manage S’s life. The people above tell S to take medicine, and S takes it. 2) S does not know what kind of medication S is consuming, but recently S has been having a hard time walking;S has people who care for S’s foot and look after S. S thinks taking medicine is for living. 3) S feel some drugs is ineffective. However, S met some people S could trust who passionately recommended the medication to S. S started being careful in remembering to take it. 4) S does not think drugs are necessary for S, but S can interact with people and spend S’s days. S has people who accept S as S is. S continues living in the community while taking medicine that a doctor offers. 5) S was skeptical about the drugs. However, S has a person S can trust, who recommended a way to take the medication in a way that S does not feel overwhelmed. S thinks that it may be a good idea to take it. Conclusions: Based on the analysis of the narratives of each of the five participants, the essential structure was read from the perspective of a third party regarding participants’ medication adherence. A generalized reading of the structure common to the above five essential structures reveals a structure that includes the following three opportunities: 1) Patients realize the importance of people;2) They sometimes entrust themselves to people or follow people’s opinions when taking actions;3) They have come to terms with their initial negative feelings about antipsychotic drugs, subsequently continuing to take antipsychotic drugs. This suggests that the following are important attitudes of supporters of patients with schizophrenia who continue to live in the community: To accept what is happening to the patients, to talk to them with encouragement and compassion, and to be there for them. It is also important for supporters to make patients feel comfortable in opening up while the patients reside in the community and to support patients in making decisions.

Active components of Bupleuri Radix in the treatment of schizophrenia analyzed by network pharmacology and clinical verification

Background:Bupleuri Radix is a common Chinese medicinal material in traditional Chinese medicine.Currently,the therapeutic effect of treating schizophrenia is relatively well understood.However,there are fewer studies examining the underlying mechanisms of its treatment.The objective of the study was to investigate the primary mechanisms of Bupleuri Radix in treating schizophrenia through network pharmacology and clinical validation.Method:Network pharmacology revealed possible molecular mechanisms,followed by clinical verification.Sixty-seven schizophrenia patients undergoing treatment at the Hunan Brain Hospital between October and November 2022 were recruited and randomly divided into the olanzapine group and the olanzapine+Bupleuri Radix group.Additionally,32 healthy people undergoing physical examinations during the same period were included as the control group.The patient’s positive and negative symptom scale scores were compared.qPCR was used to detect the mRNA expression levels of ESR1,mTOR,EIF4E,and SMAD4 in peripheral blood.Results:Through network pharmacological analysis,it was concluded in this study that Bupleuri Radix might regulate the mTOR,PI3K-Akt,and HIF-1 signaling pathways.Clinical experiments indicated that compared with before treatment,the positive and negative symptom scale scores and total scores of the two treatment groups were significantly decreased after treatment(P<0.01).In addition,the positive and negative symptom scale scores and total scores in the olanzapine+Bupleuri Radix group were significantly decreased(P<0.01)compared to the olanzapine group after treatment.Before treatment,ESR1 mRNA expression levels in peripheral blood were significantly higher in the two treatment groups than in the control group,whereas the mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly lower(P<0.01).The mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly higher after therapy than before treatment,whereas the mRNA expression levels of ESR1 in peripheral blood were significantly lower(P<0.01).After therapy,the olanzapine+Bupleuri Radix group’s mRNA expression levels of mTOR,EIF4E,and SMAD4 were significantly higher than those of the olanzapine group,whereas the mRNA expression levels of ESR1 were significantly lower(P<0.01).Conclusion:The mechanism of Bupleuri Radix’s therapeutic efficacy in schizophrenia may involve the up-regulation of mTOR,EIF4E,and SMAD4 mRNA expression and the down-regulation of ESR1 mRNA expression in peripheral blood.

A Comparison of Quality of Life, Medication Side-Effect and Adherence among Schizophrenia Patients on Conventional versus Atypical Antipsychotics

Quality of life (QoL) is becoming a widely accepted schizophrenia management outcome. But it is still not very clear if there are any significant differences between the conventional and atypical antipsychotics in terms of QoL improvement among people with schizophrenia (PWS). It is also imperative that antipsychotic drug-related factors, such as medication adherence and side-effect, which could directly or indirectly affect the QoL of PWS, are determined and compared among PWS on different classes of the drugs. Data were collected on Socio-demographic Characteristics, Quality of Life and Medication adherence using Socio-demographic and Schizophrenia Clinical Characteristics questionnaire, World Health Organization Quality of Life (WHOQoL)-Brief, and Morisky Medication Adherence Scale (MMAS) respectively from 250 respondents attending a tertiary health center’s Psychiatric clinic in Kano, Nigeria. Although PWS on the two classes of antipsychotic drugs showed inequalities in different aspects and domains of QoL, as well as in the levels of adherence and side-effects, the differences were all insignificant. However, presence of drug side effects was significantly associated with lower health-related QoL in the conventional antipsychotics group (p = 0.001), and lower score in the physical domain of QoL in the atypical antipsychotics group (p = 0.044). Medication adherence was found to be associated with better scores in different domains of QoL in both groups of PWS. There are no significant differences in terms of QoL, medication side-effect and adherence among PWS on the two classes of antipsychotics. However, drug side-effects and adherence were significantly and respectively associated with lower and higher scores in different domains of QoL in both groups.

Clinical Study on the Combination of Dingjing Pills and Risperidone in the Treatment of Patients with Schizophrenia Accompanied by Risky Behaviors

[Objectives]To observe the clinical efficacy of Dingjing Pills on patients with schizophrenia accompanied by risky behaviors.[Methods]Two hundred patients diagnosed with schizophrenia and risky behaviors were divided into two groups based on the random and double-blinded principle:the treatment group(100 cases)treated with Dingjing Pills combined with risperidone,and the control group(100 cases)treated with risperidone alone.The observation course was 6 weeks.The clinical efficacy was compared using brief psychiatric rating scale(BPRS),modified overt aggression scale(revised edition)(MAOS),treatment emergent symptom scale(TESS),and blood routine,liver function,kidney function,and electrocardiogram examinations were conducted.[Results]After treatment,Dingjing Pills significantly reduced the scores of brief psychiatric rating scale,modified overt aggression scale and treatment emergent symptom scale in patients with schizophrenia and dangerous behaviors,and had no significant toxic or side effects.The total effective rate in the treatment group was 88.8%,while the total effective rate in the control group was 77.1%.There was a significant difference in therapeutic efficacy between the two groups(P<0.05).[Conclusions]Dingjing Pills has an intervention and therapeutic effect on high-risk behaviors of schizophrenia,with minimal side effects and easy acceptance by patients.

“Too Soon on Earth”: A Biophilosophical Model of Schizophrenia. Some Implications for Humanoid Robots

This paper presents a new explanatory model for schizophrenia based upon philosophical, molecular and neurobiological hypotheses as well as on years of experience in observing and treating these patients. To start with, a novel interpretation of the Hegelian concept of mediation is presented. Mediation is defined as the rejection of non-realizable programs, such as thoughts and ideas, at a certain point in time in the evolution of a living system. Whenever a system treats non-realizable programs as if they were realizable, its ability to “test the reality” is lost, and consequently a loss of ego-boundaries may occur. On the molecular level, I will try to show how “non-splicing” of introns during the mRNA splicing process is equivalent to a loss of the rejection function corresponding to mediation. At the cellular level in the brain, mediation can be explained in terms of glial-neuronal interactions. Glia exert a spatio-temporal boundary setting function determining the grouping of neurons into functional units. Mutations in genes that result in non-splicing of introns can produce truncated (“chimeric”) neurotransmitter receptors. I propose that such dysfunctional receptors are generated in glial cells and that they cannot interact properly with their cognate neurotransmitters. The glia will then lose their inhibitory-rejecting function with respect to the information processing within neuronal networks. This loss of glial boundary setting could be an explanation for the loss of ego or body boundaries in schizophrenia. Pertinent examples of case studies are given attempting to deduce the main symptoms of schizophrenia from the proposed hypothesis. Some implications for the design of delusional robots are also discussed. Finally, the evolutionary potency of non-coding introns is philosophically interpreted that schizophrenics may be “too soon on earth”.

Safety and effectiveness of lurasidone in the treatment of Chinese schizophrenia patients:An interim analysis of post-marketing surveillance

BACKGROUND Schizophrenia is a psychiatric disorder characterized by chronic or recurrent symptoms.Lurasidone was licensed in China in 2019 for the treatment of adult schizophrenia in adults with a maximum dose of 80 mg/d.However,post-market surveillance(PMS)with an adequate sample size is required for further validation of the drug’s safety profile and effectiveness.AIM To conduct PMS in real-world clinical settings and evaluate the safety and effectiveness of lurasidone in the Chinese population.METHODS A prospective,multicenter,open-label,12-wk surveillance was conducted in China's Mainland.All patients with schizophrenia from 10 sites who had begun medication with lurasidone between September 2019 and August 2022 were eligible for enrollment.Safety assessments included adverse events(AEs),adverse drug reactions(ADRs),extrapyramidal symptoms(EPS),akathisia,use of EPS drugs,weight gain,and laboratory values as metabolic parameters and the QTc interval.The effectiveness was assessed using the brief psychiatric rating scale(BPRS)from baseline to the end of treatment.RESULTS A total of 965 patients were enrolled in the full analysis set and 894 in the safety set in this interim analysis.The average daily dose was 61.7±19.08 mg(mean±SD)during the treatment.AEs and ADRs were experienced by 101 patients(11.3%)and 78 patients(8.7%),respectively,which were mostly mild.EPS occurred in 25 individuals with a 2.8%incidence,including akathisia in 20 individuals(2.2%).Moreover,59 patients received drugs for treating EPS during the treatment,with an incidence of 6.6%which dropped to 5.4%at the end of the treatment.The average weight change was 0.20±2.36 kg(P=0.01687)with 0.8%of patients showing a weight gain of≥7%at week 12 compared with that at the baseline.The mean values of metabolic parameters and the QTc interval at baseline and week 12 were within normal ranges.The mean changes in total BPRS scores were-8.9±9.76(n=959),-13.5±12.29(n=959),and-16.8±13.97(n=959)after 2/4,6/8,and 12 wk,respectively(P<0.001 for each visit compared with the baseline)using the last-observation-carried-forward method.CONCLUSION The interim analysis of the PMS of adult patients with schizophrenia demonstrate the safety and effectiveness of lurasidone in the Chinese population.No new safety or efficacy concerns were identified.

Correlation between cognitive impairment and metabolic imbalance of gut microbiota in patients with schizophrenia

BACKGROUND The gut microbiome interacts with the central nervous system through the gutbrain axis,and this interaction involves neuronal,endocrine,and immune mechanisms,among others,which allow the microbiota to influence and respond to a variety of behavioral and mental conditions.AIM To explore the correlation between cognitive impairment and gut microbiota imbalance in patients with schizophrenia.METHODS A total of 498 untreated patients with schizophrenia admitted to our hospital from July 2020 to July 2022 were selected as the case group,while 498 healthy volunteers who underwent physical examinations at our hospital during the same period were selected as a control group.Fluorescence in situ hybridization was employed to determine the total number of bacteria in the feces of the two groups.The cognitive function test package was used to assess the score of cognitive function in each dimension.Then,the relationship between gut microbiota and cognitive function was analyzed.RESULTS There were statistically significant differences in the relative abundance of gut microbiota at both phylum and class levels between the case group and the control group.In addition,the scores of cognitive function,such as attention/alertness and learning ability,were significantly lower in the case group than in the control group(all P<0.05).The cognitive function was positively correlated with Actinomycetota,Bacteroidota,Euryarchaeota,Fusobacteria,Pseudomonadota,and Saccharibacteria,while negatively correlated with Bacillota,Tenericutes,and Verrucomicrobia at the phylum level.While at the class level,the cognitive function was positively correlated with Class Actinobacteria,Bacteroidia,Betaproteobacteria,Proteobacteria,Blastomycetes,and Gammaproteobacteria,while negatively correlated with Bacilli,Clostridia,Coriobacteriia,and Verrucomicrobiae.CONCLUSION There is a relationship between the metabolic results of gut microbiota and cognitive function in patients with schizophrenia.When imbalances occur in the gut microbiota of patients,it leads to more severe cognitive impairment.

Brain-derived neurotrophic factor, sex hormones and cognitive decline in male patients with schizophrenia receiving continuous antipsychotic therapy

BACKGROUND There are systematic differences in clinical features between women and men with schizophrenia(SCZ).The regulation of sex hormones may play a potential role in abnormal neurodevelopment in SCZ.Brain-derived neurotrophic factor(BDNF)and sex hormones have complex interacting actions that contribute to the etiology of SCZ.AIM To investigate the influence of BDNF and sex hormones on cognition and clinical symptomatology in chronic antipsychotic-treated male SCZ patients.METHODS The serum levels of follicle-stimulating hormone,luteinizing hormone(LH),estradiol(E2),progesterone,testosterone(T),prolactin(PRL)and BDNF were compared between chronic antipsychotic-treated male(CATM)patients with SCZ(n=120)and healthy controls(n=120).The Positive and Negative Syndrome Scale was used to quantify SCZ symptoms,while neuropsychological tests were used to assess cognition.Neuropsychological tests,such as the Digit Cancellation Test(DCT),Semantic Verbal Fluency(SVF),Spatial Span Test(SS),Paced Auditory Serial Addition Test(PASAT),Trail Making Task(TMT-A),and Block Design Test(BDT),were used to assess executive functions(BDT),attention(DCT,TMT-A),memory(SS,PASAT),and verbal proficiency(SVF).RESULTS Although E2 levels were significantly lower in the patient group compared to the healthy controls,T,PRL,and LH levels were all significantly higher.Additionally,the analysis revealed that across the entire sample,there were positive correlations between E2 Levels and BDNF levels as well as BDNF levels and the digital cancellation time.In CATM patients with SCZ,a significant correlation between the negative symptoms score and PRL levels was observed.CONCLUSION Sex hormones and BDNF levels may also be linked to cognitive function in patients with chronic SCZ.

Signal Conducting System with Effective Optimization Using Deep Learning for Schizophrenia Classification

Signal processing based research was adopted with Electroencephalogram(EEG)for predicting the abnormality and cerebral activities.The proposed research work is intended to provide an automatic diagnostic system to determine the EEG signal in order to classify the brain function which shows whether a person is affected with schizophrenia or not.Early detection and intervention are vital for better prognosis.However,the diagnosis of schizophrenia still depends on clinical observation to date.Without reliable biomarkers,schizophrenia is difficult to detect in its early phase and hence we have proposed this idea.In this work,the EEG signal series are divided into non-linear feature mining,classification and validation,and t-test integrated feature selection process.For this work,19-channel EEG signals are utilized from schizophrenia class and normal pattern.Here,the datasets initially execute the splitting process based on raw 19-channel EEG into 6250 sample point’s sequences.With this process,1142 features of normal and schizophrenia class patterns can be obtained.In other hand,157 features from each EEG patterns are utilized based on Non-linear feature extraction process where 14 principal features can be identified in terms of considering the essential features.At last,the Deep Learning(DL)technique incorporated with an effective optimization technique is adopted for classification process called a Deep Convolutional Neural Network(DCNN)with mayfly optimization algorithm.The proposed technique is implemented into the platform of MATLAB in order to obtain better results and is analyzed based on the performance analysis framework such as accuracy,Signal to Noise Ratio(SNR),Mean Square Error,Normalized Mean Square Error(NMSE)and Loss.Through comparison,the proposed technique is proved to a better technique than other existing techniques.