Meta-analysis of cognitive function in Chinese first-episode schizophrenia: MATRICS Consensus Cognitive Battery (MCCB) profile of impairment

Background Compromised neurocognition is a core feature of schizophrenia. With increasing studies researching cognitive function of Chinese patients with first-episode schizophrenia (FES) using MATRICS Consensus Cognitive Battery (MCCB), it is not clear about the level and pattern of cognitive impairment among this population. Aim To provide a meta-analysis systematically analysing studies of neurocognitive function using MCCB in Chinese patients with FES. Methods An independent literature search of both Chinese and English databases up to 13 March 2019 was conducted by two reviewers. Standardised mean difference (SMD) was calculated using the random effects model to evaluate the effect size. Results 56 studies (FES=3167, healthy controls (HC)=3017) were included and analysed. No study was rated as 'high quality' according to Strengthening the Reporting of Observational Studies in Epidemiology. Compared with HCs, Chinese patients with FES showed impairment with large effect size in overall cognition (SMD=-1.60,95% Cl -1.82 to -1.38,厂=67%) and all seven cognitive domains, with the SMD ranging from -0.87 to -1.41. In nine MCCB subtests, patients with FES showed significant difference in Symbol Coding (SMD=-1.90), Trail Making Test (TMT)(SMD=-1.36), Continuous Performance Test-Identical Pairs (SMD=-1.33), Hopkins Verbal Learning Test (SMD=-1.24), Brief Visuospatial Memory Test (SMD=-1.18), Mazes (SMD=-1.16), Category Fluency (SMD=-1.01), Spatial Span (SMD=-0.69) and Mayer-Salovey-Caruso Emotional Intelligence Test (SMD=-0.38). Conclusions Our meta-analysis demonstrates that Chinese patients with FES show neurocognitive deficits across all seven MCCB cognitive domains and all nine subtests, particularly in two neurocognitive domains: speed of processing and attention/vigilance, with the least impairment shown in social cognition. Symbol Coding and TMT may be the most sensitive tests to detect cognitive deficit in Chinese patients with FES.

Adjunctive aripiprazole for antipsychotic-related hyperprolactinaemia in patients with first-episode schizophrenia:a metaanalysis

Background Hyperprolactinaemia is a common antipsychotic(AP)-induced adverse effect,particularly in female patients.Aims This meta-analysis examined the efficacy and safety of adjunctive aripiprazole in preventing AP-related hyperprolactinaemia in patients with first-episode schizophrenia.Methods PubMed,PsycINFO,EMBASE,Cochrane Library,WanFang and China Journal Net databases were searched to identify eligible randomised controlled trials(RCTs).Primary outcomes were the reductions of serum prolactin level and prolactin-related symptoms.Data were independently extracted by two reviewers and analysed using RevMan(V.5.3).Weighted/standardised mean differences(WMDs/SMDs)±95%Cis were reported.Results In the five RCTs(n=400),the adjunctive aripiprazole(n=197)and the control groups(n=203)with a mean of 11.2 weeks of treatment duration were compared.The aripiprazole group had a significantly lower endpoint serum prolactin level in all patients(five RCTs,n=385;WMD:-50.43 ng/mL(95%Cl:-75.05 to-25.81),p<0.00001;l2=99%),female patients(two RCTs,n=186;WMD:-22.58 ng/mL(95%Cl:-25.67 to-19.49),p<0.00001;l2=0%)and male patients(two RCTs,n=127;WMD:-68.80 ng/mL(95%Cl:-100.11 to-37.49),p<0.0001).In the sensitivity analysis for the endpoint serum prolactin level in all patients,the findings remained significant(p<0.00001;l2=96%).The aripiprazole group was s叩erior to the control group in improving negative symptoms as assessed by the Positive and Negative Syndrome Scale(three RCTs,n=213;SMD:-0.51(95%Cl:-0.79 to-0.24),p=0.0002;l2=0%).Adverse effects and discontinuation rates were similar between the two groups.Conclusions Adjunctive aripiprazole appears to be associated with reduced AP-induced hyperprolactinaemia and improved prolactin-related symptoms in first-episode schizophrenia.Further studies with large sample sizes are needed to confirm these findings.

Prepulse inhibition deficits in antipsychotic-na-ve first-episode schizophrenia:a meta-analysis

Objective:Published studies have found prepulse inhibition(PPI)in schizophrenia is impaired,suggesting PPI may be a biomarker of schizophrenia.We aim to examine whether PPI deficits exist in antipsychotic-na-ve,first-episode schizophrenia,and evaluate the effect size of PPI deficits between patients and healthy controls.Methods:The effect size of PPI deficits was evaluated for PPI%by calculating standard mean differences(SMDs)between patients with antipsychotic-na-ve,first-episode schizophrenia and healthy controls.Results:Twelve studies met the inclusion criteria,consisting390antipsychotic-na-ve,first-episode schizophrenia and406healthy controls.The effect sizes of76dB PPI in60ms and120ms interstimulus interval(ISI)were-0.19and-0.41respectively,and the76dB PPI overall effect size was-0.30.The effect sizes of85/86dB PPI in30ms,60ms and120ms ISI were-0.25,-0.42and-0.59respectively,and the85/86dB PPI overall effect size was-0.46.One study were excluded due to heterogeneity in the85/86dB,120ms ISI group,the pooled effect size of the PPI differences between patient group and health control dropped to-0.42,and the overall effect size changed to-0.39.There were no statistical differences in startle magnitude(overall effect size=-0.18)and habituation%(overall effect size=-0.17)between patients and healthy controls.Conclusions:Antipsychotic-na-ve,first-episode schizophrenia patients exhibit robust and reliable deficits in PPI,85/86dB PPI deficit was more severe than76dB PPI,and85/86dB,60-ms ISI PPI was more likely to be a biomarker for schizophrenia,it suggested that the parameters of PPI are particularly significant to affect the effect size so that should be interpreted with cautions in the future studies.

FOLLOW-UP STUDY ON AUDITORY EVOKED POTENTIAL P50 IN FIRST-EPISODE SCHIZOPHRENIA

Objective To investigate the variation of auditory evoked potential P50 in first-episode schizo- phrenia. Methods P50 was recorded from 66 schizophrenics and 92 normal controls with American Brova instrument, and assessing their psychotic symptoms with PANSS. Results Compared with NC, schizophrenics showed sensory gating deficit, reflecting by increased S2/S1 ratio (NC: 42±21% , Sch:81±40% ,P <0. 01). No significant correlation was found between PANSS score and the three markers for assessing the sensory gating, such as the S2/S1 ratio, S2-S1, and 100 (1 -S2/S1) (P > 0. 05). Schizophrenics showed no differences with P50 markers between the 5 weeks and 12 weeks of treatment. Conclusion P50 might be biological trait marker of schizophrenia.

Sensory Gating of Patients with First-Episode Schizophrenia

Objective To observe the characteristics of sensory gating P50 in patients with first-episode schizophrenia(Sch). Methods Auditory evoked potentials P50 were recorded in 92 normal controls(NC)and 66 schizophrenia patients by the conditioning/testing paradigm presented with auditory double clicks stimuli, using American Nicolet Bravo instrument. Results Compared with NC, schizophrenia patients showed decreased S1-P50 amplitude(NC:[6±3]μV, Sch: [3±2]μV, P<0.01), increased S2-P50 amplitude(NC: [2±1]μV, Sch: [4±2]μV, P<0.01), higher S2/S1 ratio(NC: [42±21]%, Sch: [81±40]%, P<0.01), decreased S2-S1(NC: [3±2]μV, Sch: [2±1]μV, P<0.05) and 100(1-S2/S1) (NC: [58±21]%, Sch: [19±17]%, P<0.01), suggesting that patients had sensory gating deficits. Conclusion The first-episode schizophrenia patients had sensory gating deficits, reflecting by auditory evoked potential P50.

Comparison of Treatment Effect of Resperidone on First-Episode Schizophrenia Patients at Different Ages and its Influencing Factor Analysis

Objectives To explore the treatment effect of risperidone on patients with firstepisode schizophrenia at different ages and analyze its influencing factors.Methods fifty cases of adult patients with the first-episode schizophrenia(adult group)and forty cases of juvenile patients with the firstepisode schizophrenia(juvenile group)treated in our hospital from March 2013 to March 2015 were selected for oral administration of risperidone.The clinical efficacy,adverse effect,brief psychiatric rating scale(BPRS)score before and after the therapy,brain-derived neurotrophic factor(BDNF)and blood lipid level were compared between the two groups after eight weeks’treatment with risperidone,and meanwhile,the multivariable linear regression analysis was performed to the related factors possibly influencing the efficacy of risperidone.Results The difference of total effective rate between the adult group(86%)and the juvenile group(82.5%)was not significant(P>0.05).The total score of BPRS,TC,TG,and LDL-C levels in the two groups after the treatment were significantly decreased compared with that before the treatment,while BDNF was significantly increased.The difference of inter-group comparison was significant before and after the treatment(P>0.05).However,the comparison difference between two groups was not significant before and after the treatment(P>0.05).The multivariable linear regression equation was used to analyze the longer duration of untreated psychosis(DUP),BPRS total score before treatment and BDNF levels that influence the efficacy of risperidone on patients with schizophrenia.Conclusion the treatment efficacy of risperidone on adult patients and juvenile patients with first-episode schizophrenia was similar and it was safe and effective.The DUP,BPRS total score before treatment and BDNF levels were associated with the efficacy of risperidone.

MiRNA-365 and miRNA-520c-3p respond to risperidone treatment in first-episode schizophrenia after a 1 year remission

Background MicroRNAs （miRNAs） control gene expression by destabilizing target transcripts and inhibiting their translation. Aberrant expression of miRNAs has been described in many human diseases, including schizophrenia. However, the effects on miRNA expression in response to antipsychotic treatment in peripheral circulation have not been thoroughly examined. Methods Using quantitative real-time PCR （qRT-PCR）, We quantified the expression of seven candidate miRNAs in plasma samples of 40 first-episode schizophrenics before and after antipsychotic treatment. The patients were all treated with risperidone and achieved remission in 1 year. Results Compared with the baseline, the expression levels of miR-365 and miR-520c-3p were significantly down- regulated after 1 year of risperidone treatment （P 〈0.001）. There were no significant correlations between the clinical symptoms and the expression levels of these two miRNAs （P 〉0.05）. Conclusions This study analyzed possible circulating miRNAs in response to antipsychotic monotherapy for schizophrenia, the further mechanism need to be confirmed.

Neurocognitive Graphs of First-Episode Schizophrenia and Major Depression Based on Cognitive Features

Neurocognitive deficits are frequently observed in patients with schizophrenia and major depressive disorder(MDD). The relations between cognitive features may be represented by neurocognitive graphs based on cognitive features, modeled as Gaussian Markov random fields. However, it is unclear whether it is possible to differentiate between phenotypic patterns associated with the differential diagnosis of schizophrenia and depression using this neurocognitive graph approach. In this study, we enrolled 215 first-episode patients with schizophrenia(FES), 125 with MDD, and 237 demographically-matched healthy controls(HCs). The cognitive performance of all participants was evaluated using a battery of neurocognitive tests. The graphical LASSO model was trained with aone-vs-one scenario to learn the conditional independent structure of neurocognitive features of each group. Participants in the holdout dataset were classified into different groups with the highest likelihood. A partial correlation matrix was transformed from the graphical model to further explore the neurocognitive graph for each group. The classification approach identified the diagnostic class for individuals with an average accuracy of 73.41% for FES vs HC, 67.07% for MDD vs HC, and 59.48% for FES vs MDD. Both of the neurocognitive graphs for FES and MDD had more connections and higher node centrality than those for HC. The neurocognitive graph for FES was less sparse and had more connections than that for MDD.Thus, neurocognitive graphs based on cognitive features are promising for describing endophenotypes that may discriminate schizophrenia from depression.

Effects of Risperidone and Paliperidone on Brain-Derived Neurotrophic Factor and N400 in First-Episode Schizophrenia

Background：Risperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor （BDNF） and N400 （an event-related brain potential component）.So far,different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments.However,few studies have been conducted on the mechanism ofrisperidone and paliperidone on BDNF and N400.This study aimed to compare the effects ofrisperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia.Methods：Ninety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone,respectively,for 12 weeks.Serum BDNF level,the latency,and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale （PANSS） scores were compared between the two groups.Results：A total of 94 patients were included in the final analysis （47 patients in each group）.After the treatment,the serum BDNF levels in both groups increased （all P 〈 0.01）,while no significant difference in serum BDNF level was found between the groups before and after the treatment （all P 〉 0.05）.After the treatment,N400 amplitudes were increased （from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv,respectively） under congruent condition in both risperidone and paliperidone groups （all P 〈 0.01）.Under incongruent conditions,the N400 latencies were shortened in the paliperidone group （from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms,P 〈 0.05）,and the N400 amplitudes were increased in the risperidone group （from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv,P 〈 0.01）.After treatment,the total PANSS score in both groups decreased significantly （all P 〈 0.01）,but the difference between the groups was not significant （P 〉 0.05）.A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group.Conclusions：Both risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function （N400 latency and amplitude）,but their antipsychotic mechanisms might differ.

The burden of depression,anxiety and schizophrenia among the older population in ageing and aged countries:an analysis of the Global Burden of Disease Study 2019

Background Depression,anxiety and schizophrenia among older persons have become global public health challenges.However,the burden of these disorders in ageing and aged countries has not been analysed.Aims To investigate the burden of depression,anxiety and schizophrenia among older adults in ageing and aged countries.Methods Using data from the Global Burden of Disease Study 2019,we calculated the estimated annual percentage change(EAPC)in the age-standardised incidence rates(ASiR)and age-standardised disability-adjusted life years(DALYs)rates(ASDR)for depression,anxiety and schizophrenia of older people in ageing countries(China,India,Indonesia)and aged countries(Japan,Italy,Portugal)between 1990 and 2019.Trends in incidence and DALYs were analysed by gender and age.Results In 2019,the highest incidence of depression,anxiety and schizophrenia in the older population in aged countries was in Japan(927271.3(752552.3-1125796.5),51498.2(37625.7-70487.3)and 126.0(61.0-223.2),respectively),while the highest incidence in ageing countries was in China(5797556.9(4599403.4-7133006.5),330256.1(246448.9-445987.4)and 1067.7(556.2-1775.9),respectively).DALYs for these disorders were similar,with the highest in Japan and China.From 1990 to 2019,the ASIR for depressive disorders decreased in aged countries but increased in ageing countries;the ASIR for anxiety disorders and schizophrenia declined in both ageing and aged countries.The ASDR for depressive disorders was consistent with the ASIR but not for anxiety disorders and schizophrenia.The ASIR for depressive disorders was higher in older women,while the opposite was observed in anxiety disorders and schizophrenia.Notably,the conditions of burden of depressive disorders,anxiety disorders and schizophrenia in the 65-70-year-old age group were the most burdensome.Conclusions The incidence and DALYs of these three mental disorders increased while exhibiting differences between ageing and aged countries.Raising awareness about formulating health policies for preventing and treating mental disorders in the older population is necessary to reduce the future burden posed by the ageing challenge.

Follow-up of N400 in the Rehabilitation of First-episode Schizophrenia

Background：The N400 component of event-related potentials （ERP） has recently drawn widespread attention at home and abroad.This study was to explore the relationship between N400 changes and risperidone treatment and rehabilitation in first-episode schizophrenia （FES）.Methods：ERP component N400 was recorded by Guangzhou Runjie W J-l ERP instruments,in 58 FES before and 6 months,15 months after risperidone treatment,and in 62 normal controls.The patients＇ syndromes were assessed by Positive and Negative Syndrome Scale （PANSS）.And the stimuli are Chinese sentences with matching （congruent） or mismatching （incongruent） ending words.Results：N400 latencies were prolonged,and amplitudes were decreased in Cz,Pz,Fz,C3,C4,in FES compared with in NC,before treatment.The prolonged N400 latencies and decreased amplitudes were negatively correlated with the patients＇ positive scale and total scale of PANSS.There are significant differences of N400 amplitudes and latencies in 6 months and 15 months follow-up after treatment.Before treatment,6 months and 15 months after treatment,N400 latencies are 446 ± 35 ms,440 ± 37 ms,414 ± 31 ms （F =9.72,P 〈 0.01） in incongruent situation;N400 amplitudes are 5.2 ± 4.6 μtⅤ,5.7 ± 4.8 μⅤ,7.3 ± 5.0 μⅤ （F =2.06,P 〉 0.05） in congruent situation,and 8.5 ± 5.9 μⅤ,10.1 ± 5.0 μⅤ,11.9 ± 7.0 μⅤ （F =3.697,P 〈 0.05） in incongruent situation.Conclusions：N400 could be used to predict the effects of treatment of schizophrenia to some degree.The linguistic and cognitive impairment in schizophrenia can be improved by antipsychotic drugs.

Altered asymmetries of resting-state MRI in the left thalamus of first-episode schizophrenia

Background:Schizophrenia(SCZ)is a complex psychiatric disorder associated with widespread alterations in the subcortical brain structure.Hemispheric asymmetries are a fundamental organizational principle of the human brain and relate to human psychological and behavioral characteristics.We aimed to explore the state of thalamic lateralization of SCZ.Methods:We used voxel-based morphometry(VBM)analysis,whole-brain analysis of low-frequency fluctuations(ALFF),fractional amplitude of low-frequency fluctuations(fALFF),and resting-state seed-based functional connectivity(FC)analysis to investigate brain structural and functional deficits in SCZ.Also,we applied Pearson’’s correlation analysis to validate the correlation between Positive and Negative Symptom Scale(PANSS)scores and them.Results:Compared with healthy controls,SCZ showed increased gray matter volume(GMV)of the left thalamus(t=2.214,p=0.029),which positively correlated with general psychosis(r=0.423,p=0.010).SCZ also showed increased ALFF in the putamen,the caudate nucleus,the thalamus,fALFF in the nucleus accumbens(NAc),and the caudate nucleus,and decreased fALFF in the precuneus.The left thalamus showed significantly weaker resting-state FC with the amygdala and insula in SCZ.PANSS negative symptom scores were negatively correlated with the resting-state FC between the thalamus and the insula(r=-0.414,p=0.025).Conclusions:Collectively,these results suggest the possibility of aberrant laterality in the left thalamus and its FC with other related brain regions involved in the limbic system.

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.

Research Progress on the Association between Schizophrenia and Toxoplasma gondii Infection

Toxoplasma gondii(T.gondii or Tg),is an obligatory intracellular parasite with humans as its intermediate hosts.In recent years,significant correlations between T.gondii infection and schizophrenia have been reported,including the possible mediating mechanisms.Currently,mechanisms and hypotheses focus on central neurotransmitters,immunity,neuroinflammation,and epigenetics;however,the exact underlying mechanisms remain unclear.In this article,we review the studies related to T.gondii infection and schizophrenia,particularly the latest research progress.Research on dopamine(DA)and other neurotransmitters,the blood-brain barrier,inflammatory factors,disease heterogeneity,and other confounders is also discussed.In addition,we also summarized the results of some new epidemiological investigations.

Navigating personal recovery:multinomial logistic regression analysis of schizophrenia outcomes in community-dwelling individuals

Background Schizophrenia is a chronic mental disorder affecting individuals globally,emphasising the significance of personal recovery in mental healthcare.Understanding the recovery stages and the associated factors can provide essential insights for targeted interventions.Aims This study aimed to discern the stages of personal recovery in Thai patients with schizophrenia and elucidate the associated factors with each stage.Methods A multistage sampling technique was employed,selecting 231 patients with schizophrenia from mental health outpatient departments of general and psychiatric hospitals.Data collected from March to May 2023 included screening for psychotic symptoms using the Brief Psychiatric Rating Scale and six self-report questionnaires—Stage of Recovery Scale,Beck Cognitive Insight Scale,Brief Resilience Scale,Family Support,Therapeutic Relationship-Patients Version and Social Support Questionnaire—along with personal data sheets.Pearson correlation and multinomial logistic regression were performed.Results The predominant personal recovery stage among participants was stage 3,‘living with disabilities’,comprising 42.4%of the participants.Key factors contributing to personal recovery,explaining approximately 38.4%of the variance,included resilience,family support,therapeutic alliance,hospitalisations since onset and recovery-oriented nursing service utilisation.Logit equations for stages 3 and 4 are as follows:stage 3(living with disability):logit=−4.44+0.74×resilience+0.07×therapeutic alliance+0.02×recovery-oriented nursing service utilisation;stage 4(living beyond disability):logit=−11.57-0.05×hospitalisation since onset+1.96×resilience+0.11×family support+0.06×therapeutic alliance.Conclusion The findings emphasise the significance of mental health nursing interventions.In conjunction with recovery-oriented nursing services,strengthening resilience,therapeutic alliances and family support may accelerate personal recovery and reduce hospitalisations among individuals with schizophrenia.

New role of platelets in schizophrenia:predicting drug response

Background Elevated platelet count(PLTc)is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis.However,the impact of antipsychotic medications on PLTc and its association with symptom improvement remain unclear.Aims We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related variables.Methods A total of 2985 patients with schizophrenia were randomised into seven groups.Each group received one of seven antipsychotic treatments and was assessed at 2,4 and 6 weeks.Clinical symptoms were evaluated using the positive and negative syndrome scale(PANSS).Additionally,we measured blood cell counts and metabolic parameters,such as blood lipids.Repeated measures analysis of variance was used to examine the effect of antipsychotics on PLTc changes,while structural equation modelling was used to assess the predictive value of PLTc on PANSS changes.Results PLTc significantly increased in patients treated with aripiprazole(F=6.00,p=0.003),ziprasidone(F=7.10,p<0.001)and haloperidol(F=3.59,p=0.029).It exhibited a positive association with white blood cell count and metabolic indicators.Higher baseline PLTc was observed in non-responders,particularly in those defined by the PANSS-negative subscale.In the structural equation model,PLTc,white blood cell count and a latent metabolic variable predicted the rate of change in the PANSS-negative subscale scores.Moreover,higher baseline PLTc was observed in individuals with less metabolic change,although this association was no longer significant after accounting for baseline metabolic values.Conclusions Platelet parameters,specifically PLTc,are influenced by antipsychotic treatment and could potentially elevate the risk of venous thromboembolism in patients with schizophrenia.Elevated PLTc levels and associated factors may impede symptom improvement by promoting inflammation.Given PLTc’s easy measurement and clinical relevance,it warrants increased attention from psychiatrists.Trial registration number ChiCTR-TRC-10000934.

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.