The linking of toxoplasmosis and schizophrenia.

Toxoplasmosis is caused by Toxoplasma gondii (Nicolle et Manceaux, 1908), a coccidian protist (Apicomplexa). It has a strong predilection for infecting the central nervous system. Researchers have therefore investigated its association with several neurological and psychiatric disorders, including Alzheimer's disease, attention-deficit hyperactivity disorder, autism, bipolar disorder, cerebral palsy, depression, Guillain-Barre syndrome, multiple sclerosis, obsessive compulsive disorder, Parkinson's disease, personality disorders, and schizophrenia. Among these disorders the strongest evidence for a role of T. gondii exists for psychosis in general and schizophrenia in particular. This paper reviews the origins of this association, briefly summarises the current evidence in support, and discusses future research strategies.

Antipsychotic prescription patterns among schizophrenia patients in Guangdong Province, China's 686 program: A retrospective study.

Schizophrenia is a severe mental disorder. However, there is limited data on the prescribing patterns of patients under China's Central Government Support for the Local Management and Treatment of Severe Mental Illnesses Program, known as the "686 program." This study aimed to investigate the use of antipsychotic medications and associated factors among discharged schizophrenia patients in Guangdong Province, within the 686 Program. This study encompassed schizophrenia patients who were discharged from the Affiliated Brain Hospital, Guangzhou Medical University and enrolled in the 686 Program between January 2019 and December 2019. A total of 1645 hospitalized schizophrenia patients were included in the analysis. Clinical and sociodemographic data were acquired from medical records upon discharge. A total of 15 unique antipsychotic medications were utilized, comprising 4 first-generation (FGAs) and 11 second-generation (SGAs) options. FGAs were prescribed at a rate of 8.3%, while SGAs dominated at 98.8%. Risperidone (40.8%), olanzapine (30.2%), clozapine (24.6%), and amisulpride (15.4%) emerged as the top 4 prescribed medications. Additionally, mood stabilizers were used by 20.4%, antidepressants by 14.8%, sedative-hypnotics by 33.6%, anticholinergics by 26.9%, and other internal medicine drugs by 46.4%. Notably, 60.5% received antipsychotic monotherapy (AMT), while 39.5% underwent antipsychotic polypharmacy (APP). Predictors of polypharmacy included multiple hospital admissions, longer hospital stays, and undergoing modified Electroconvulsive Therapy (mECT) during hospitalization. In Guangdong Province, China's 686 Program, hospitalized patients commonly receive multiple antipsychotic medications simultaneously. Due to the varying outcomes in current studies on the benefits and risks of polypharmacy, it's vital to educate psychiatrists about the importance of AMT to reduce APP. Additionally, randomized, controlled trials are essential to identify the safest and most effective antipsychotic combinations, as well as to understand which patient profiles may benefit from these combinations.

Integrative Neuro-social cognitive Strategy Programme for Instilling REcovery (INSPIRE): a community-based cognitive remediation trial-study procotol.

BACKGROUND: Adults with schizophrenia experience a range of neurocognitive problems that affect their daily functioning. Evidence for the efficacy of cognitive remediation in schizophrenia has been established, but its implementation in under-resourced community-based settings is less well-studied. In recent years, interventions have also focused on the strategy-learning approach in favor of drill-and-practice. Moreover, there is an increasing recognition to address social cognition and negative symptoms alongside neurocognition. This study attempts to carry out cognitive remediation in a community mental health setting. The Neuropsychological and Educational Approach to Remediation (NEAR) is used as the cognitive remediation intervention. Neurocognitive and social cognitive games will be introduced during the computer-assisted cognitive exercises sessions. In addition, the instructional technique will foster the use of metacognition and cognitive strategies. Moreover, metamotivation training will be the focus of some bridging sessions to enhance motivation to engage in goal-directed learning behaviors. The aims of the study are to 1) investigate the effects of cognitive remediation on neurocognition, social cognition and functional outcomes of participants with schizophrenia/schizoaffective disorders in community mental health settings; and 2) explore the mediators for change (eg: metamotivation, metacognition and negative symptoms) in cognitive performance and functional outcomes. METHODS: This randomized controlled trial will be conducted in three Singapore Anglican Community Services (SACS) centers, where standard psychiatric rehabilitation is delivered. Participants who are randomized to the experimental arm will receive cognitive remediation and psychiatric rehabilitation, while those randomized to the control arm will receive standard psychiatric rehabilitation only. Cognitive remediation is carried out three times a week for 12 weeks. It consists of computer-assisted cognitive exercises, as well as bridging groups to aid transfer of learning to daily living. Baseline, post-intervention and eight-week follow-up measurements will be collected. Group by time differences in cognitive performance, negative symptoms, metamotivation, metacognition, functioning and recovery will be analyzed across the three time points. Mediators for improvement in cognitive performance and functioning will also be explored. DISCUSSION: Findings of this research will add to the body of knowledge about the key therapeutic ingredients within a strategy-based cognitive remediation program and improve its implementation within under-resourced community settings. TRIAL REGISTRATION: This study has been registered with ClinicalTrials.gov (ID: NCT06286202). Date of registration: 29 February 2024. Date of last update: 21 May 2024.

Cariprazine in Psychiatry: A Comprehensive Review of Efficacy, Safety, and Therapeutic Potential.

This article provides a comprehensive review of recent developments regarding a new atypical antipsychotic drug - cariprazine - considering the mechanism of action, efficacy, safety, and promising therapeutic option for various psychiatric disorders, including schizophrenia and bipolar disorder, therapy of addictions, and treatment in the pediatric population. Its distinct pharmacological profile, characterized by partial agonism at dopamine D2 and D3 receptors, as well as serotonin receptors - 5HT1A with a preference for the D3 receptor - sets it apart from other antipsychotics. The unique mechanism of action contributes to cariprazine's positive impact on negative symptoms in schizophrenia and an antidepressant effect. Its relatively low risk of adverse effects, such as sedation, metabolic issues, and hypotension, enhances its tolerability. In bipolar affective disorder, cariprazine exhibits effectiveness in managing both depressive and manic episodes. Ongoing research in pediatric populations suggests potential benefits in schizophrenia, bipolar I disorder, and autism spectrum disorder, but further research is necessary to establish safety and efficacy. Moreover, cariprazine shows promise in addiction therapy, particularly with coexisting psychiatric disorders. Continued research and clinical exploration may discover additional insights, broadening its use in diverse patient populations. This article aims to review the role of cariprazine, a dopamine D2/D3 and serotonin 5-HT1A receptor partial agonist, in the management of psychotic illnesses, including schizophrenia, bipolar disorder, addiction therapy, and pediatric treatment.

Prevalence of spontaneous movement disorders (dyskinesia, parkinsonism, akathisia and dystonia) in never-treated patients with chronic and first-episode psychosis: a systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis is to evaluate and compare the prevalence rates of spontaneous movement disorders (SMDs), including dyskinesia, parkinsonism, akathisia and dystonia, in antipsychotic-naïve individuals with chronic psychosis and first-episode psychosis (FEP) and gain a more nuanced understanding of factors influencing their presence. METHODS: Several literature databases were systematically searched and screened based on predetermined eligibility criteria. Included articles underwent risk of bias assessment. The prevalence rates of SMDs were calculated using a random-effects model. RESULTS: Out of 711 articles screened, 27 were included in this meta-analysis. The pooled prevalence of spontaneous dyskinesia was 7% (3% FEP and 17% chronic schizophrenia) across 24 studies (95% CI 3 to 11; I2=94%, p<0.01) and 15% for spontaneous parkinsonism (14% FEP and 19% chronic schizophrenia) in 21 studies (95% CI 12 to 20; I2=81%, p<0.01). A meta-regression analysis found a significant positive correlation between age (p<0.05) and duration of untreated psychosis (DUP) (p<0.05) with dyskinesia but not parkinsonism prevalence. Akathisia and dystonia appear to be both less studied and less frequent in occurrence with a pooled prevalence of 4% (95% CI: 3 to 6; I2=0%, p=0.65) for akathisia in eight studies and a mean prevalence of 6% (range 0%-16%) for dystonia in five studies. CONCLUSION: The presence of varying degrees of neurodysfunction in antipsychotic-naïve patients with schizophrenia underscores the need for individualised treatment approaches that consider each patient's unique predisposition and neuromotor profile. Further research is warranted into the role of specific SMDs and risk factors including sex, race and diagnostic variations. PROSPERO REGISTRATION NUMBER: CRD42024501951.

The prognosis of schizophrenia.

Psychotic and negative symptoms are core features of schizophrenia but knowledge on the long-term course of these symptoms is lacking. While antipsychotics improve psychotic symptoms, they have limited effect on negative symptoms. Specialized early interventions like OPUS show great effects while ongoing but long-term follow-up indicates no lasting disease-modifying effects. 18% of patients achieved clinical recovery, and 40% obtained symptom remission after 20 years, but high mortality rates and continuous negative symptoms constitute an unmet treatment need, as argued in this review.

Prevalence of schizophrenia spectrum and other psychotic disorders in problem gambling: A systematic review and meta-analysis.

BACKGROUND: High rates of psychiatric comorbidities have been found in people with problem gambling (PBG), including substance use, anxiety, and mood disorders. Psychotic disorders have received less attention, although this comorbidity is expected to have a significant impact on the course, consequences, and treatment of PBG. This review aimed to estimate the prevalence of psychotic disorders in PBG. METHODS: Medline (Ovid), EMBASE, PsycINFO (Ovid), CINAHL, CENTRAL, Web of Science, and ProQuest were searched on November 1, 2023, without language restrictions. Studies involving people with PBG and reporting the prevalence of schizophrenia spectrum and other psychotic disorders were included. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal checklist for systematic reviews of prevalence data. The pooled prevalence of psychotic disorders was calculated using a random effects generalized linear mixed model and presented with forest plots. RESULTS: Of 1,271 records screened, 22 studies (n = 19,131) were included. The overall prevalence of psychotic disorders was 4.9% (95% CI, 3.6-6.5%, I2 = 88%). A lower prevalence was found in surveyed/recruited populations, compared with treatment-seeking individuals and register-based studies. No differences were found for factors such as treatment setting (inpatient/outpatient), diagnoses of psychotic disorders (schizophrenia only/other psychotic disorders), and assessment time frame (current/lifetime). The majority of included studies had a moderate risk of bias. CONCLUSIONS: These findings highlight the relevance of screening problem gamblers for schizophrenia spectrum and other psychotic disorders, as well as any other comorbid mental health conditions, given the significant impact such comorbidities can have on the recovery process.

Higher levels of AKT-interacting protein in the frontal pole from people with schizophrenia are limited to a sub-group who have a marked deficit in cortical muscarinic M1 receptors.

We are studying the molecular pathology of a sub-group within schizophrenia (∼ 25 %: termed Muscarinic Receptor Deficit subgroup of Schizophrenia (MRDS)) who can be separated because they have very low levels of cortical muscarinic M1 receptors (CHRM1). Based on our transcriptomic data from Brodmann's area ((BA) 9, 10 and 33 (controls, schizophrenia and mood disorders) and the cortex of the CHRM1-/- mouse (a molecular model of aberrant CHRM1 signaling), we predicted levels of AKT interacting protein (AKTIP), but not tubulin alpha 1b (TUBA1B) or AKT serine/threonine kinase 1 (AKT1) and pyruvate dehydrogenase kinase 1 (PDK1) (two AKTIP-functionally associated proteins), would be changed in MRDS. Hence, we used Western blotting to measure AKTIP (BA 10: controls, schizophrenia and mood disorders; BA 9: controls and schizophrenia) plus TUBA1B, AKT1 and PDK1 (BA 10: controls and schizophrenia) proteins. The only significant change with diagnosis was higher levels of AKTIP protein in BA 10 (Cohen's d = 0.73; p = 0.02) in schizophrenia compared to controls due to higher levels of AKTIP only in people with MRDS (Cohen's d = 0.80; p = 0.03). As AKTIP is involved in AKT1 signaling, our data suggests that signaling pathway is particularly disturbed in BA 10 in MRDS.

Feuerstein Instrumental Enrichment Program for People With Schizophrenia After the First Episode of Psychosis: Protocol for an Open-Label Intervention Study.

BACKGROUND: Schizophrenia is a disorder associated with neurocognitive deficits that adversely affect daily functioning and impose an economic burden. Cognitive rehabilitation interventions, particularly during the early phases of illness, have been shown to improve cognition, functionality, and quality of life. The Feuerstein Instrumental Enrichment (FIE) program, based on the Mediated Learning Experience and the Structural Cognitive Modifiability theory, has been applied in various disorders, but its applicability in schizophrenia has not yet been clarified. OBJECTIVE: This study aims to investigate the effects of the FIE program on the functionality of patients with first-episode schizophrenia. METHODS: In total, 17 patients will be recruited for an open-label intervention consisting of twice-weekly sessions for 10 weeks. The primary outcome measure will be changes in the Goal Achievement Scale score. Maze task performance from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery will serve as a secondary outcome measure. At the same time, changes in Positive and Negative Syndrome Scale scores and other MATRICS domains will be analyzed as exploratory outcomes. Assessments will be administered before and after the intervention, with a follow-up period of 6 months. RESULTS: This trial was preregistered in The Brazilian Registry of Clinical Trials (RBR-4gzhy4s). By February 2024, 11 participants were enrolled in the training. Recruitment is expected to be completed by May 2024. Data analysis will be conducted between May and September 2024. The results are expected to be published in January 2025. CONCLUSIONS: This study may establish a protocol for the FIE program that uses mediation techniques for individuals in the early stages of schizophrenia. The results will add to the knowledge about strategies to promote cognitive skills and functional impairment in daily life. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57031.

Randomized open-label study of second-generation antipsychotics for the treatment of schizophrenia: 104-week final results of the JUMPs study assessing treatment discontinuation, remission, and social functioning.

BACKGROUND: We report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study. METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension). RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p < 0.05) in QOL and total PANSS scores (including all subscales) was observed at Week 104 compared with baseline. Multivariable analysis identified a shorter disease duration and a higher chlorpromazine-equivalent antipsychotic dosage level (≥ 1000 mg) before switching to monotherapy as predictors of treatment discontinuation. CONCLUSIONS: The 104-week treatment outcomes were comparable between groups; the overall trend of improvement in remission rate, safety, and QOL suggests the importance of continued treatment. CLINICAL TRIAL REGISTRATION: UMIN-Clinical Trials Registry UMIN000007942 (public release date: 14/05/2012).

Functioning Management and Recovery, a psychoeducational intervention for psychiatric residential facilities: a multicenter follow-up study.

AIM: Functional Management and Recovery is a standardized Psychoeducational Intervention, derived from "Integro", an effective salutogenic-psychoeducational intervention for people in recovery journey, designed to improve recovery and functioning of individuals with psychotic disorders in Psychiatric Residential Facilities (PRFs). The aim of this study is to evaluate the primary and secondary outcomes of this intervention elaborated specifically for PRFs where evidence based structured interventions seem rare and desirable. METHODS: 66 individuals with psychotic disorders were recruited in 9 PRFs dislocated in the North, Center and South Italy and 63 underwent a multicenter follow-up study with a two time-point evaluation (t0, pre-treatment and t1, 6 months; ). At each time point, social functioning was assessed as primary outcome by the Personal and Social Performance scale (PSP); furthermore, psychopathological status was assessed by Brief Psychiatric Rating Scale (BPRS), Recovery by Recovery Assessment Scale (RAS), Cognitive Functioning by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Stress management by Stress-Scale, Cognitive Flexibility by Modified Five-Point Test (M-FPT), Emotional Intelligence by Emotional Intelligence Index (EI-I), the PRF Atmosphere and the Opinion of users about the PFR by an ad hoc questionnaire. The Abilities Knowledge, the Utility and Pleasantness of sessions were measured by an ad hoc list of items. RESULTS: 63 individuals out of 66, 52 (82,5%) affected by schizophrenia and 11 (17,5%) by bipolar I disorder with psychotic symptoms according to DSM-5-TR completed the study. At the end of the study, 43 (68,3%) were male, 57 (90.5%) were single, 5 (7.9%) engaged, 1 (1.6%) married; 45 (71.4%) unemployed. The total scores of PSP, RAS, BPRS, BANS, Stress management, Abilities Knowledge, Utility and Pleasantness of sessions showed a statistically significant improvement at t1 vs. t0. Two sub-scales out of 5 of M-FPT showed a statistically significant improvement. The Emotional Intelligence, the Unit Atmosphere and the Opinion of Users about PFR improved without statistical significance. Six months after the end of the follow-up study 22 individuals of the sample were dismissed with a very high turnover. CONCLUSIONS: After a six-month follow-up (a short period of time), these results showed improvement in functioning, the primary outcome, as well as in the following secondary outcome variables: RAS, BPRS, BANS, Stress management, Abilities Knowledge, two sub-scales out of 5 of M-FPT, Utility and Pleasantness of sessions. Overall, a remarkable impact of psychoeducational structured intervention on the key Recovery variables is observed. Further studies are needed to address extent and duration of these improvements.

Impact of Biological Sex on Emotional Perception Among Adults With Schizophrenia Spectrum Disorders: Protocol for a Systematic Review.

BACKGROUND: It is well established that individuals with schizophrenia experience deficits in emotional perception that can impact long-term social and occupational functioning. Understanding the factors that impact these impairments is important for targeting interventions to improve recovery. In the general population, compared with males, females tend to show greater perception of emotions. Whether this sex difference persists in schizophrenia is less clear. In contrast to males, females diagnosed with schizophrenia tend to have a higher age of disease onset and better premorbid functioning but do not necessarily have better outcomes. Effective treatments for social cognitive impairments are highly relevant to long-term functional rehabilitation. A greater understanding of the cognitive deficits in emotional perception within females and males living with schizophrenia may assist interventions to be better tailored to individuals. OBJECTIVE: This systematic review aims to collate, synthesize, and critically appraise evidence considering the influence of biological sex (female and male) on the emotional perception of individuals with schizophrenia. METHODS: This is a systematic review protocol based on the PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) guidelines. The electronic databases MEDLINE, Embase, CENTRAL, CINAHL, and PsycINFO will be systematically searched. To be included in this review, studies must compare the emotional perceptions of male and female participants older than 18 years who have a primary diagnosis of a schizophrenia spectrum disorder. Qualitative studies, case reports, case series, unpublished manuscripts, and studies not reported in English will be excluded. Key search strategies will include combinations of the following terms: "men," "male," "man," "female," "women," "woman," "sex," "gender," "emotional perception," "emotional processing," "schizophrenia," "schizophren," "psychotic disorders," "psychosis," "psychoses," "psychotic," "schizoaffective," "schizotypal personality disorder," and "schizotyp." Identified studies will be uploaded to the web-based Covidence systematic review management software. The risk of bias for individual studies will be assessed using the relevant Joanna Briggs Institute checklist tools. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system will also be used to evaluate the strength of the evidence base. Findings will be synthesized to provide a systematic summary of the existing literature. If sufficiently comparable data to permit meta-analysis emerges, a random-effects meta-analysis will be performed. RESULTS: This systematic review was registered with the PROSPERO (International Prospective Register of Systematic Reviews) in October 2023. The search and screening of study titles and abstracts are currently underway. Data are expected to be extracted and analyzed in July 2024. CONCLUSIONS: Results will contribute to an improved understanding of the social cognitive profiles of males and females with schizophrenia. This knowledge is expected to inform the adaptation of interventions to improve functional outcomes. TRIAL REGISTRATION: PROSPERO CRD42023463561; https://tinyurl.com/34sr3rnf. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56977.

Direct targets of MEF2C are enriched for genes associated with schizophrenia and cognitive function and are involved in neuron development and mitochondrial function.

Myocyte Enhancer Factor 2C (MEF2C) is a transcription factor that plays a crucial role in neurogenesis and synapse development. Genetic studies have identified MEF2C as a gene that influences cognition and risk for neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia (SCZ). Here, we investigated the involvement of MEF2C in these phenotypes using human-derived neural stem cells (NSCs) and glutamatergic induced neurons (iNs), which represented early and late neurodevelopmental stages. For these cellular models, MEF2C function had previously been disrupted, either by direct or indirect mutation, and gene expression assayed using RNA-seq. We integrated these RNA-seq data with MEF2C ChIP-seq data to identify dysregulated direct target genes of MEF2C in the NSCs and iNs models. Several MEF2C direct target gene-sets were enriched for SNP-based heritability for intelligence, educational attainment and SCZ, as well as being enriched for genes containing rare de novo mutations reported in ASD and/or developmental disorders. These gene-sets are enriched in both excitatory and inhibitory neurons in the prenatal and adult brain and are involved in a wide range of biological processes including neuron generation, differentiation and development, as well as mitochondrial function and energy production. We observed a trans expression quantitative trait locus (eQTL) effect of a single SNP at MEF2C (rs6893807, which is associated with IQ) on the expression of a target gene, BNIP3L. BNIP3L is a prioritized risk gene from the largest genome-wide association study of SCZ and has a function in mitophagy in mitochondria. Overall, our analysis reveals that either direct or indirect disruption of MEF2C dysregulates sets of genes that contain multiple alleles associated with SCZ risk and cognitive function and implicates neuron development and mitochondrial function in the etiology of these phenotypes.

Risk factors for violent crime in patients with schizophrenia: a retrospective study.

Introduction: The relationship between schizophrenia and violence is heterogeneous and complex. The aim of this study was to explore the characteristics and the potential risk factors for violence crime in patients with schizophrenia. Methodology: We conducted a retrospective case-control study at the Judicial Psychiatric Identification Unit of Xiangya Second Hospital of Central South University from January 1, 2013 to December 31, 2016. The case group included violent offenders diagnosed with schizophrenia, while the control group comprised non-violent individuals with the same diagnosis. Results: There were 308 individuals in the violent group [subdivided into the homicide group (n = 155) and the intentional injury group (n = 153)] and 139 individuals in the non-violent group. A risk model showed that a history of violence (odds ratio (OR) = 2.88, 95% CI [1.79-4.64]), persecutory delusions (OR = 2.57, 95% CI [1.63-4.06]), regular treatment in the previous four weeks (OR = 0.29, 95% CI [0.16-0.51]) and insight (OR = 0.30, 95% CI [0.14-0.62]) were independently associated with violence. Conclusion: This study provided useful clinical information to identify risk factors for violence and develop better strategic programs to manage violence in patients with schizophrenia.

Psychological interventions for early-phase schizophrenia: protocol for a systematic review and network meta-analysis.

Introduction: Treating the early phase of schizophrenia is crucial for preventing further episodes and improving quality of life, functioning, and social inclusion. Pharmacotherapies are first-line treatments, but have limitations. There is consensus on the need for non-pharmacological interventions for individuals in the early phase of schizophrenia. Several psychological interventions have shown promising effects; however, their comparative effectiveness remains largely unknown. To address this issue, a network meta-analysis will be performed. We aim to develop a hierarchy of existing psychological treatments concerning their efficacy and tolerability, which will inform treatment guidelines. Protocol: Randomized controlled trials (RCTs) investigating psychological interventions for first-episode psychosis, first-episode schizophrenia, or early phase schizophrenia will be included. The primary outcome will be overall schizophrenia symptoms (measured up to 6 and 12 months, and at the longest follow-up) and relapse as a co-primary outcome. Secondary outcomes are premature discontinuation; change in positive, negative, and depressive symptoms of schizophrenia; response; quality of life; overall functioning; satisfaction with care; adherence; adverse events; and mortality. The study selection and data extraction are performed by two independent reviewers. We will assess the risk of bias of each study using the Cochrane Risk of Bias tool 2 and evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). Subgroup and sensitivity analyses will be conducted to explore heterogeneity and assess the robustness of our findings. Discussion: This systematic review and network meta-analysis aims to compare multiple existing psychological interventions, establishing which are best for symptom reduction, relapse prevention, and other important outcomes in early phase schizophrenia. Our results may provide practical guidance concerning the most effective psychological intervention to reduce symptom severity and the societal burden associated with the disorder.

Local-structure-preservation and redundancy-removal-based feature selection method and its application to the identification of biomarkers for schizophrenia.

Accurate diagnosis of mental disorders is expected to be achieved through the identification of reliable neuroimaging biomarkers with the help of cutting-edge feature selection techniques. However, existing feature selection methods often fall short in capturing the local structural characteristics among samples and effectively eliminating redundant features, resulting in inadequate performance in disorder prediction. To address this gap, we propose a novel supervised method named local-structure-preservation and redundancy-removal-based feature selection (LRFS), and then apply it to the identification of meaningful biomarkers for schizophrenia (SZ). LRFS method leverages graph-based regularization to preserve original sample similarity relationships during data transformation, thus retaining crucial local structure information. Additionally, it introduces redundancy-removal regularization based on interrelationships among features to exclude similar and redundant features from high-dimensional data. Moreover, LRFS method incorporates l2,1 sparse regularization that enables selecting a sparse and noise-robust feature subset. Experimental evaluations on eight public datasets with diverse properties demonstrate the superior performance of our method over nine popular feature selection methods in identifying discriminative features, with average classification accuracy gains ranging from 1.30 % to 9.11 %. Furthermore, the LRFS method demonstrates superior discriminability in four functional magnetic resonance imaging (fMRI) datasets from 708 healthy controls (HCs) and 537 SZ patients, with an average increase in classification accuracy ranging from 1.89 % to 9.24 % compared to other nine methods. Notably, our method reveals reproducible and significant changes in SZ patients relative to HCs across the four datasets, predominantly in the thalamus-related functional network connectivity, which exhibit a significant correlation with clinical symptoms. Convergence analysis, parameter sensitivity analysis, and ablation studies further demonstrate the effectiveness and robustness of our method. In short, our proposed feature selection method effectively identifies discriminative and reliable features that hold the potential to be biomarkers, paving the way for the elucidation of brain abnormalities and the advancement of precise diagnosis of mental disorders.

Blood metabolites, neurocognition and psychiatric disorders: a Mendelian randomization analysis to investigate causal pathways.

BACKGROUND: Neurocognitive dysfunction is observationally associated with the risk of psychiatric disorders. Blood metabolites, which are readily accessible, may become highly promising biomarkers for brain disorders. However, the causal role of blood metabolites in neurocognitive function, and the biological pathways underlying their association with psychiatric disorders remain unclear. METHODS: To explore their putative causalities, we conducted bidirectional two-sample Mendelian randomization (MR) using genetic variants associated with 317 human blood metabolites (nmax = 215,551), g-Factor (an integrated index of multiple neurocognitive tests with nmax = 332,050), and 10 different psychiatric disorders (n = 9,725 to 807,553) from the large-scale genome-wide association studies of European ancestry. Mediation analysis was used to assess the potential causal pathway among the candidate metabolite, neurocognitive trait and corresponding psychiatric disorder. RESULTS: MR evidence indicated that genetically predicted acetylornithine was positively associated with g-Factor (0.035 standard deviation units increase in g-Factor per one standard deviation increase in acetylornithine level; 95% confidence interval, 0.021 to 0.049; P = 1.15 × 10-6). Genetically predicted butyrylcarnitine was negatively associated with g-Factor (0.028 standard deviation units decrease in g-Factor per one standard deviation increase in genetically proxied butyrylcarnitine; 95% confidence interval, -0.041 to -0.015; P = 1.31 × 10-5). There was no evidence of associations between genetically proxied g-Factor and metabolites. Furthermore, the mediation analysis via two-step MR revealed that the causal pathway from acetylornithine to bipolar disorder was partly mediated by g-Factor, with a mediated proportion of 37.1%. Besides, g-Factor mediated the causal pathway from butyrylcarnitine to schizophrenia, with a mediated proportion of 37.5%. Other neurocognitive traits from different sources provided consistent findings. CONCLUSION: Our results provide genetic evidence that acetylornithine protects against bipolar disorder through neurocognitive abilities, while butyrylcarnitine has an adverse effect on schizophrenia through neurocognition. These findings may provide insight into interventions at the metabolic level for risk of neurocognitive and related disorders.