Models of mild cognitive deficits in risk assessment in early psychosis.

BACKGROUND: Mild cognitive deficits (MCD) emerge before the first episode of psychosis (FEP) and persist in the clinical high-risk (CHR) stage. This study aims to refine risk prediction by developing MCD models optimized for specific early psychosis stages and target populations. METHODS: A comprehensive neuropsychological battery assessed 1059 individuals with FEP, 794 CHR, and 774 matched healthy controls (HCs). CHR subjects, followed up for 2 years, were categorized into converters (CHR-C) and non-converters (CHR-NC). The MATRICS Consensus Cognitive Battery standardized neurocognitive tests were employed. RESULTS: Both the CHR and FEP groups exhibited significantly poorer performance compared to the HC group across all neurocognitive tests (all p < 0.001). The CHR-C group demonstrated poorer performance compared to the CHR-NC group on three sub-tests: visuospatial memory (p < 0.001), mazes (p = 0.005), and symbol coding (p = 0.023) tests. Upon adjusting for sex and age, the performance of the MCD model was excellent in differentiating FEP from HC, as evidenced by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.895 (p < 0.001). However, when applied in the CHR group for predicting CHR-C (AUC = 0.581, p = 0.008), the performance was not satisfactory. To optimize the efficiency of psychotic risk assessment, three distinct MCD models were developed to distinguish FEP from HC, predict CHR-C from CHR-NC, and identify CHR from HC, achieving accuracies of 89.3%, 65.6%, and 80.2%, respectively. CONCLUSIONS: The MCD exhibits variations in domains, patterns, and weights across different stages of early psychosis and diverse target populations. Emphasizing precise risk assessment, our findings highlight the importance of tailored MCD models for different stages and risk levels.

Correlative relationship between body mass index and heart rate variability in psychiatric disorders.

OBJECTIVE: Indicators of heart rate variability (HRV) have been used to assess the autonomic activity. However, the influence of obesity on HRV in these patients remains to be determined. This study aimed to examine how obesity (measured with the body mass index [BMI]) affects HRV and determine whether the effect varies among different psychiatric disorders. We recruited 3159 consecutive patients, including 1744 with schizophrenia, 966 with mood disorders, and 449 with anxiety disorders. Patients were divided into four groups based on BMI: underweight (< 18.5), normal weight (18.5-23.9), overweight (24-27.9), and obese (≥ 28). The cardiovascular status was assessed using several time- and frequency-based HRV indicators, measured via electrocardiogram signals recorded for 5 min. The mean BMI of the participants was 23.6 ± 4.0. The patients in the overweight and obese groups were 29.4% and 13.6% of the total, respectively. The HRV indicators were higher in underweight and normal-weight patients than in the overweight and obese ones. After stratification based on the psychiatric diagnosis, the patients with mood disorders showed lower HRV than those with schizophrenia or anxiety disorder in the normal-weight group. In contrast, in the overweight and obese groups the patients with mood disorders showed higher HRV than those with the other disorders. The HRV variables were significantly associated with BMI, and higher BMI was associated with higher heart rates and lower HRV. These results indicate that weight gain in psychiatric disorders is associated with an imbalance in autonomic nerve activity. However, the relationship between autonomic activity, weight gain, and psychiatric disorders warrants further investigation.

Association between serum cytokines and timeframe for conversion from clinical high-risk to psychosis.

AIM: Although many studies have explored the link between inflammatory markers and psychosis, there is a paucity of research investigating the temporal progression in individuals at clinical high-risk (CHR) who eventually develop full psychosis. To address this gap, we investigated the correlation between serum cytokine levels and Timeframe for Conversion to Psychosis (TCP) in individuals with CHR. METHODS: We enrolled 53 individuals with CHR who completed a 5-year follow-up with a confirmed conversion to psychosis. Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) levels were measured at baseline and 1-year. Correlation and quantile regression analyses were performed. RESULTS: The median TCP duration was 14 months. A significantly shorter TCP was associated with higher levels of TNF-α (P = 0.022) and VEGF (P = 0.016). A negative correlation was observed between TCP and TNF-α level (P = 0.006) and VEGF level (P = 0.04). Quantile regression indicated negative associations between TCP and GM-CSF levels below the 0.5 quantile, IL-10 levels below the 0.3 quantile, IL-2 levels below the 0.25 quantile, IL-6 levels between the 0.65 and 0.75 quantiles, TNF-α levels below the 0.8 quantile, and VEGF levels below the 0.7 quantile. A mixed linear effects model identified significant time effects for IL-10 and IL-2, and significant group effects for changes in IL-2 and TNF-α. CONCLUSIONS: Our findings underscore that a more pronounced baseline inflammatory state is associated with faster progression of psychosis in individuals with CHR. This highlights the importance of considering individual inflammatory profiles during early intervention and of tailoring preventive measures for risk profiles.

Effects of polygenic risk of schizophrenia on interhemispheric callosal white matter integrity and frontotemporal functional connectivity in first-episode schizophrenia.

BACKGROUND: Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported. METHODS: Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts. RESULTS: Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)-left inferior temporal gyrus (ITG), right IFG-left ITG, right IFG-left middle frontal gyrus (MFG), and right IFG-right MFG in the FES group. CONCLUSION: Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.

Serum angioneurin levels following electroconvulsive therapy for mood disorders.

OBJECTIVES: The efficacy of electroconvulsive therapy (ECT) in treating mood disorders (MDs) is hypothesized to be mediated by the induction of neurotrophic factors (denoted "angioneurins") that trigger neuronal plasticity. This study aimed to assess the effects of ECT on serum angioneurin levels in patients with MD. METHODS: A total of 110 patients with MDs including 30 with unipolar depression, 25 with bipolar depression (BD), 55 with bipolar mania (BM), and 50 healthy controls were included in the study. Patients were subdivided into two groups: those who received ECT + medication (12 ECT sessions) and those who received only medication (no-ECT). Depressive and manic symptom assessments and measurements of vascular endothelial growth factor (VEGF), fibroblast growth factor-2, nerve growth factor (NGF), and insulin-like growth factor-1 levels in blood samples were performed at baseline and week 8. RESULTS: Patients in the ECT group, specifically those with BD and BM, had significantly increased levels of VEGF compared to their baseline VEGF levels (p = 0.002). No significant changes in angioneurin levels were observed in the no-ECT group. Serum NGF levels were significantly associated with a reduction in depressive symptoms. Angioneurin levels were not associated with manic symptom reduction. CONCLUSIONS: This study hints that ECT may increase VEGF levels with angiogenic mechanisms that amplify NGF signaling to promote neurogenesis. It may also contribute to changes in brain function and emotional regulation. However, further animal experiments and clinical validation are needed.

Changes in Inflammatory Markers in Clinical High Risk of Developing Psychosis.

INTRODUCTION: Immune alterations are associated with the progression of psychosis. However, there are few studies designed to longitudinally measure inflammatory biomarkers during psychotic episodes. We aimed to assess changes in biomarkers from the prodromal phase to psychotic episodes in individuals with clinical high risk (CHR) of psychosis and compare converters and non-converters to psychosis as well as healthy controls (HCs). METHODS: We enrolled 394 individuals with CHR and 100 HCs. A total of 263 individuals with CHR completed the 1-year follow-up, and 47 had converted to psychosis. Interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor levels were measured at baseline and 1 year after completion of the clinical assessment. RESULTS: The baseline serum levels of IL-10, IL-2, and IL-6 were significantly lower in the conversion group than in the non-conversion group (IL-10, p = 0.010; IL-2, p = 0.023; IL-6, p = 0.012) and HC (IL-6: p = 0.034). Self-controlled comparisons showed that IL-2 changed significantly (p = 0.028), and IL-6 levels tended toward significance (p = 0.088) in the conversion group. In the non-conversion group, serum levels of TNF-α (p = 0.017) and VEGF (p = 0.037) changed significantly. Repeated measures analysis of variance revealed a significant time effect related to TNF-α (F = 4.502, p = 0.037, effect size (η2) = 0.051), a group effect related to IL-1ß (F = 4.590, p = 0.036, η2 = 0.062), and IL-2 (F = 7.521, p = 0.011, η2 = 0.212), but no time × group effect. DISCUSSION: Alterations in the serum levels of inflammatory cytokines were found to precede the first episode of psychosis in the CHR population, particularly for those who later converted to psychosis. Longitudinal analysis supports the varied roles of cytokines in individuals with CHR with later psychotic conversion or non-conversion outcomes.

Microcystins-Loaded Aged Nanoplastics Provoke a Metabolic Shift in Human Liver Cells.

Studies concerning the toxicity of pollutant-loaded nanoplastics (NPs) toward humans are still in their infancy. Here, we evaluated the adsorption of microcystins (MCs) by pristine and aged polystyrene nanoplastics (PSNPs), prepared MCs-loaded aged PSNPS (1, 5, 10, 15, and 19 µg/mg), and systematically mapped the key molecular changes induced by aged and MCs-loaded PSNPs to human hepatoblastoma (HepG2) cells. According to the results, MC-LR adsorption is increased 2.64-fold by aging, and PSNP accumulation is detected in HepG2 cells. The cytotoxicity of the MC-LR-loaded aged PSNPs showed a positive relationship with the MC-LR amount, as the cell viability in the 19 µg/mg loading treatment (aPS-MC19) was 10.84% lower than aged PSNPs; meanwhile, more severe oxidative damage was observed. Primary approaches involved stressing the endoplasmic reticulum and reducing protein synthesis that the aged PSNPs posed for HepG2 cells, while the aggravated cytotoxicity in aPS-MC19 treatment was a combined result of the metabolic energy disorder, oxidative damage, endoplasmic reticulum stress, and downregulation of the MC-LR target protein. Our results confirm that the aged PSNPs could bring more MC-LR into the HepG2 cells, significantly interfere with biological processes, and provide new insight into deciphering the risk of NPs to humans.

Attenuated niacin response is associated with a subtype of first-episode drug-naïve psychosis characterized as serious negative symptoms.

Although the phenomenon of attenuated niacin response (ANR) has been widely replicated in some patients with first-episode psychosis (FEP), its relevance to the negative symptoms (NS) of psychosis remains unclear. Total of 240 patients with drug-naïve FEP and 101 healthy controls (HCs) were recruited, and 209 were followed up for 1 year. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and niacin-induced responses were measured using laser Doppler flowmetry. We calculated the log-transform EC50 [concentration of methyl nicotinate required to elicit a half-maximal blood flow (MBF) response] and MBF values. Core-NS was generated by factor analysis of the PANSS-NS subscale and cluster analysis to produce subtypes. Significant differences were found in the log10 (EC50) values between the FEP and HC groups (p < 0.001), supporting the ANR in patients with FEP. A higher NS severity was found in the ANR subgroup than that in other patients. Factor analysis determined that a two-dimensional model included core NS and rigidity of thinking. The log10 (EC50) value was significantly associated with only the core NS. Cluster analysis revealed three subtypes-36.7% (cluster-1, n = 88), 16.7% (cluster-2, n = 40), and 46.7% (cluster-3, n = 112). Cluster-2 characterized by extensive NS appeared to have a more remarkable ANR and less symptomatic improvement than those with other clusters during follow-up. No significant changes were found in the niacin response trajectories between the baseline and follow-up. Our findings indicate a significant correlation between ANR and core NS in patients with FEP. ANR may be a potential biomarker for certain subtypes with NS-dominated characteristics and poor symptomatic remission.

Potential disintegration and transport of biochar in the soil-water environment: A case study towards purple soil.

Biochar has been widely applied in soil and water. However, the fate and transport of biochar are not yet fully understood. Here, biochar's disintegration, transport, and the effect of temperature on biochar transport in soil (purple soil)-water systems were investigated. The results showed that the potentially transportable components (PTC) of biochar for corn straw, wheat straw, rice straw, rice husk and wood biochar reached 6.22-7.60%, 5.96-12.29%, 11.77-12.45%, 5.34-6.26% and 5.08-6.14% by mass, respectively. An external force (ultrasound exposure) intensified the physical disintegration, including colloidal and nanoparticles from larger particles, thereby increasing the transport potential. The mass recovery rates of PTC for rice straw biochar after penetrating through soil at 5, 20 and 35 °C reached 44.25%, 32.97% and 10.98%, respectively, which was supported by the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory results. Elevated temperatures increased the hydrodynamic average diameter of PTC, and the Zeta potential of PTC and soil at 35 °C were less negative than those at 5 and 20 °C. As a result, biochar's transportability decreases with increasing temperature in the soil-water system, during which the enhanced PTC aggregation and the decreased electrostatic repulsion between biochar and soil particles played a crucial role. The increase in electrical conductivity in the soil-water system may be the main reason for the decrease in electrostatic repulsion at higher temperatures. The findings are helpful for an in-depth understanding of the environmental fate and managing the transport risk of biochar.

Discovery and engineering of small SlugCas9 with broad targeting range and high specificity and activity.

The compact CRISPR/Cas9 system, which can be delivered with their gRNA and a full-length promoter for expression by a single adeno-associated virus (AAV), is a promising platform for therapeutic applications. We previously identified a compact SauriCas9 that displays high activity and requires a simple NNGG PAM, but the specificity is moderate. Here, we identified three compact Cas9 orthologs, Staphylococcus lugdunensis Cas9 (SlugCas9), Staphylococcus lutrae Cas9 (SlutrCas9) and Staphylococcus haemolyticus Cas9 (ShaCas9), for mammalian genome editing. Of these three Cas9 orthologs, SlugCas9 recognizes a simple NNGG PAM and displays comparable activity to SaCas9. Importantly, we generated a SlugCas9-SaCas9 chimeric nuclease, which has both high specificity and high activity. We finally engineered SlugCas9 with mutations to generate a high-fidelity variant that maintains high specificity without compromising on-target editing efficiency. Our study offers important minimal Cas9 tools that are ideal for both basic research and clinical applications.

Manganese (II) sulfate affects the formation of iron-manganese oxides in soil and the uptake of cadmium and arsenic by rice.

Rice (Oryza sativa L.) consumption represents a major route of human exposure to cadmium (Cd) and arsenic (As), especially in Asia. This study investigated the effects of adding MnSO4 (0, 200, 400, and 800 mg kg-1-1) on the formation of soil Fe/Mn oxides and Cd and As uptake in rice. The application of MnSO4 reduced soil pH, increased Eh, increased the contents of Fe/Mn oxides in the soil, and decreased the total Fe and Mn2+ contents in the porewater. It also led to lower contents of available Cd and As, higher levels of Cd and As bound to Fe/Mn oxides, and higher abundances of Thiobacillus and Syntrophobacter. Furthermore, Mn application increased the Fe and Mn contents in the root Fe/Mn plaque and decreased the grain Cd and As contents. Therefore, Mn application may modify the microbial community and porewater composition in soil, resulting in higher levels of Fe/Mn oxides in soil and Fe/Mn plaque at the root surface and in a lower accumulation of Cd and As in rice grains. Thus, Mn application can be a promising strategy for Cd and As stabilization in soils.

Biochar performance for preventing cadmium and arsenic accumulation, and the health risks associated with mustard (Brassica juncea) grown in co-contaminated soils.

Cadmium (Cd) and arsenic (As) in co-contaminated soil can enter the human body harming health via the food chain, such as vegetables. Biochar derived from waste has been used to reduce heavy metal uptake by plant, but long-term effects of biochar under Cd and As co-contaminated soil needs to be investigated. A following mustard (Brassica juncea) was grown on co-contaminated soil amended with different raw materials of biochar including biochars pyrolyzed by lignite coal (LCB), rice straw (RSB), silkworm excrement (SEB), and sugar refinery sludge (SSB). The results showed that compared to the control, Cd and As contents of mustard shoot in SSB treatment decreased by 45-49% and 19-37% in two growing seasons, respectively, which was the most effective among 4 biochars. This probably due to SSB owns more abundant Fe-O functional groups. Biochar also altered the microbial community composition, specifically SSB increased proteobacteria abundance by 50% and 80% in the first and second growing seasons, thereby promoted the simultaneous immobilization of Cd and As in soils which may reduce the potential risks to humans. In summary, considering the long-term effects and security of SSB application on mustard, not only is it an effective waste recycle option, but it should also be promoted as a promising approach for safe vegetable production in Cd and As co-contaminated soils.

Effects of foliar applications of Brassinolide and Selenium on the accumulation of Arsenic and Cadmium in rice grains and an assessment of their health risk.

Arsenic and cadmium pose a potential health risk to human beings via rice grain consumption. In the current study, a pot experiment was conducted to evaluate the effect of Br (5 mM and 20 mM) and Se (1 mM) at rice tillering and filling stages on Cd and As accumulation in rice grain and their health risk indices. The results showed that Br or Se applications at different stages of rice improved the photosynthesis, reduce MDA content in flag leaves by 17.41%-38.65%, increased rice biomass and grain yield by 10.50%-29.94% and 10.50%-36.56%, and enhanced grain N and P uptake by 3.25%-34.90%, and 22.98%-72.05%, respectively. Applications of Br and Se effectively decreased Cd and As concentration in rice grain by 31.74%-86.97% and 16.42%-81.13% respectively. Compared to the individual treatment, combined 20 mM Br and 1 mM Se at the filling stage showed the lowest accumulation of As (0.149 mg·kg-1) and Cd (0.105 mg·kg-1) in grain, and its health risk index was below the acceptable limits (HRI < 1). This implies that application of Br and Se at the filling stage is a promising strategy for the safe production of rice in As and Cd co-contaminated regions.

In this study, foliar applications of Br and Se at the grain filling and tillering stage demonstrate their effect on As and Cd accumulation. The findings showed that Br and Se resulted in the Se concentration in grains reaching the Se-enriched level, and the accumulation of As and Cd was the lowest. Furthermore, the application of Br and Se decreased lipid peroxidation, promoted N and P uptake, and increased the rate of photosynthesis in the rice plants, which resulted in increasing rice growth and grain yield. The HRI of heavy metals was below the acceptable limits after application of Br and Se.

Characteristics and comparative analysis of Mesona chinensis Benth chloroplast genome reveals DNA barcode regions for species identification.

Mesona chinensis Benth (MCB) is an important medicinal and edible plant in Southern China and Southeast Asian countries. Chloroplast (cp) genome is usually used for plant phylogeny, species identification, and chloroplast genetic engineering. To characterize the cp genome and determine the evolutionary position and perform the genetic diversity analysis of MCB, we sequence and characterize the MCB cp genome. The results show that the cp genome of MCB is a single circular molecule with a length of 152,635 bp. It is a typical quadripartite structure, comprising a large single-copy region (LSC, 83,514 bp) and a small single-copy region (SSC, 17,751 bp) separated by two inverted repeat regions (IRs, 51,370 bp). It encodes 129 unique genes, including 84 protein-coding genes (PCGs), 37 transfer RNAs (tRNAs), and 8 ribosomal RNAs (rRNAs). Altogether 127 simple sequence repeats (SSRs) are identified in the MCB cp genome with 86.61% of mononucleotide repeats. Phylogenetic analysis reveals that MCB is most closely related to Ocimum basilicum based on the whole cp genomes. Several highly divergent regions are found, such as trnH_psbA, rps16_trnQ, trnS_trnG, trnE_trnT, psaA_ycf3, rpl32_trnL, ccsA_ndhD, ndhG_ndhI, and rps15_ycf1, which can be proposed for use as DNA barcode regions. Genetic diversity analysis unveils a relatively narrow genetic basis of MCB germplasm resources. Therefore, the innovative breeding of MCB is very urgent and necessary in future research.

Automatic auditory processing features in distinct subtypes of patients at clinical high risk for psychosis: Forecasting remission with mismatch negativity.

Individuals at clinical high risk (CHR) for psychosis exhibit a compromised mismatch negativity (MMN) response, which indicates dysfunction of pre-attentive deviance processing. Event-related potential and time-frequency (TF) information, in combination with clinical and cognitive profiles, may provide insight into the pathophysiology and psychopathology of the CHR stage and predict the prognosis of CHR individuals. A total of 92 individuals with CHR were recruited and followed up regularly for up to 3 years. Individuals with CHR were classified into three clinical subtypes demonstrated previously, specifically 28 from Cluster 1 (characterized by extensive negative symptoms and cognitive deficits), 31 from Cluster 2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 33 from Cluster 3 (characterized by the mildest symptoms and cognitive deficits). Auditory MMN to frequency and duration deviants was assessed. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired using TF analysis. Predictive indices for remission were identified using logistic regression analyses. As expected, reduced frequency MMN (fMMN) and duration MMN (dMMN) responses were noted in Cluster 1 relative to the other two clusters. In the TF analysis, Cluster 1 showed decreased theta and alpha ITC in response to deviant stimuli. The regression analyses revealed that dMMN latency and alpha ERSP to duration deviants, theta ITC to frequency deviants and alpha ERSP to frequency deviants, and fMMN latency were significant MMN predictors of remission for the three clusters. MMN variables outperformed behavioral variables in predicting remission of Clusters 1 and 2. Our findings indicate relatively disrupted automatic auditory processing in a certain CHR subtype and a close affinity between these electrophysiological indexes and clinical profiles within different clusters. Furthermore, MMN indexes may serve as predictors of subsequent remission from the CHR state. These findings suggest that the auditory MMN response is a potential neurophysiological marker for distinct clinical subtypes of CHR.

Pathogen load and species monitored by droplet digital PCR in patients with bloodstream infections: A prospective case series study.

BACKGROUND AND OBJECTIVES: Bloodstream infection (BSI) is a life-threatening condition in critically ill patients, but pathogen quantification techniques during treatment are laborious. This study aimed to explore the impact of monitoring pathogen DNA load changes and polymicrobial infection in blood by droplet digital polymerase chain reaction (ddPCR) on the prognosis of patients with BSIs. METHODS: This prospective case series study was conducted in the general intensive care unit of the Zhejiang Provincial People's Hospital and included patients with BSIs from May 2020 to January 2021. Pathogens DNA load and presence of polymicrobial BSIs were dynamically monitored by ddPCR. RESULTS: Sixteen patients with BSIs proven by blood culture were recruited (87.5% men; mean age, 69.3 ± 13.7 years). All pathogens identified by blood culture were Gram-negative bacteria, among which seven were multidrug-resistant strains. The 28-day mortality rate was 62.5%. Compared to the 28-day survivors, the non-survivors were older (P = 0.04), had higher pathogen DNA load on the second (day 3-4) and third (day 6-7) ddPCR assay (P < 0.01 in both cases). In addition, the changes of pathogen DNA load in the 28-day survivors had a downward trend in the first three ddPCR assay, whereas stable load or an upward trend was observed in the 28-day non-survivors. Moreover, the number of pathogen species in patients with BSIs in the 28-day survivors decreased during the period of effective antibiotic treatment. CONCLUSION: The changes of pathogen DNA load and species monitored in blood by ddPCR may be used to determine antibiotic efficacy and make a more accurate prognostic assessment in patients with BSIs.

Further evidence that antipsychotic medication does not prevent long-term psychosis in higher-risk individuals.

OBJECTIVE: Although existing guidelines have discouraged use of antipsychotics for general clinical high-risk (CHR) individuals, it is unclear if antipsychotics can prevent psychosis in higher-risk population. We aimed to study the comparative real-world effectiveness of antipsychotic treatments for preventing psychosis in higher-risk CHR individuals. METHODS: A total of 300 CHR individuals were identified using the structured interview for prodromal syndromes (SIPS) and followed the participants for 3 years. In total, 228(76.0%) individuals completed baseline assessments using the NAPLS-2 risk calculator (NAPLS-2-RC), and 210(92.1%) completed the follow-up. The sample was further stratified according to risk level. "Higher-risk" was defined based on the NAPLS-2-RC risk score (≥ 20%) and SIPS positive symptom total scores (≥ 10). The main outcome was conversion to psychosis and poor functional outcomes, defined as a global assessment of function (GAF) score lower than 60 at follow-up. RESULTS: In higher-risk CHR individuals, we found no significant difference in the rate of conversion to psychosis or poor functional outcomes between the antipsychotic and no-antipsychotic groups. Low-risk individuals treated with antipsychotic drugs were more likely exhibit poor functional outcomes compared with the no-antipsychotics group(NAPLS-2-RC estimated risk: χ2 = 8.330, p = 0.004; Positive symptom severity: χ2 = 12.997, p < 0.001). No significant effective factors were identified for prevention of the conversion to psychosis; conversely, CHR individuals who were treated with high dose antipsychotics (olanzapine, aripiprazole) showed a significantly increased risk of poor functional outcomes. CONCLUSIONS: In CHR individuals, antipsychotic treatment should be provided with caution because of the risk of poor functional outcomes. Further, antipsychotic treatment does not appear to prevent onset of psychosis in real-world settings.

Temporal and time-frequency features of auditory oddball response in distinct subtypes of patients at clinical high risk for psychosis.

Individuals at clinical high risk (CHR) for psychosis exhibit a reduced P300 oddball response, which indicates deficits in attention and working memory processes. Previous studies have mainly researched these responses in the temporal domain; hence, non-phase-locked or induced neural activities may have been ignored. Event-related potential (ERP) and time-frequency (TF) information, combined with clinical and cognitive profiles, may provide an insight into the pathophysiology and psychopathology of the CHR stage. The 104 CHR individuals who completed cognitive assessments and ERP tests were recruited and followed up between 2016 and 2018. Individuals with CHR were classified by three clinical subtypes demonstrated before, specifically 32 from Cluster-1 (characterized by extensive negative symptoms and cognitive deficits, at the highest risk for conversion to psychosis), 34 from Cluster-2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 38 from Cluster-3 (characterized by the mildest symptoms and cognitive deficits). Electroencephalograms were recorded during the auditory oddball paradigm. The P300 ERPs were analyzed in the temporal domain. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired by TF analysis. A reduced P300 response to target tones was noted in Cluster-1 relative to the other two clusters. Moreover, the P300 amplitude of Cluster-1 was associated with speed of processing (SoP) scores. Furthermore, the P300 amplitude of Cluster-3 was significantly correlated with verbal and visual learning scores. In the TF analysis, decreased delta ERSP and ITC were observed in Cluster-1; delta ITC was associated with SoP scores in Cluster-3. The results indicate relatively disrupted oddball responses in a certain CHR subtype and a close affinity between these electrophysiological indexes and attention, working memory, and declarative memory within different CHR clusters. These findings suggest that the auditory oddball response is a potential neurophysiological marker for distinct clinical subtypes of CHR.

Characteristics of platelet-associated parameters and their predictive values in Chinese patients with affective disorders.

OBJECTIVE: Platelets are increasingly considered to play an important role in inflammation and are being regarded as a putative bridge linking mental diseases and inflammatory response. Platelet-associated haematological parameters including mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR), platelet to albumin ratio (PAR) and red blood cell distribution width (RDW) to platelet ratio (RPR), have been recently investigated as simple, easily available, and inexpensive inflammatory markers. In this study, we aimed is to use large-scale clinical data to study platelet parameters in patients with affective disorders, to further investigate the predictive power of platelet parameters for major depressive disorder (MDD) and bipolar disorder (BD). METHODS: The retrospective, naturalistic, cross-sectional study analysed the data of 14,007 Chinese affective disorder patients, including 4,801 patients with first-episode MDD, 4,098 patients with recurrent MDD, 3,444 patients with BD manic episodes and 1,664 patients with BD depressive episodes. Meanwhile, 6,847 healthy subjects were served as the control group. The differences in the MPV, PDW, PCT, SII, PLR, PAR, RPR and albumin among different groups were compared, and the contributing factors for the occurrence of MDD or BD were analysed. RESULTS: There were significant differences in MPV, PDW, PCT, SII, PLR, RPR and albumin values among the study groups. In the subjects, patients experiencing BD manic episodes had the highest mean values of MPV and SII, patients experiencing BD depressive episodes had the lowest mean values of platelet counts and PAR, and patients with MDD had the highest mean values of PLR and RDW. The levels of MPV, PDW and albumin were independently correlated with MDD and BD, and they are important predictors for differentiating patients with MDD or BD from healthy controls. CONCLUSIONS: Our study demonstrated that different affective disorders have unique platelet parameter variation patterns, highlighting the role of platelet parameters and systemic inflammation in the pathophysiology of MDD and BD.

Gender differences in screening self-reported psychotic symptoms in a first help-seeking population.

Gender differences in the frequency and severity of psychotic symptoms have been widely reported. However, in the screening process for the detection of early psychosis, gender differences were largely overlooked in China. This study investigated gender differences in self-reported psychotic symptoms in a clinical population who initially visited a mental health service. In total, 1931 consecutive new patients were included in the current analysis, with a mean age of 25.3 years, including 852 (44.1%) men and 1079 (55.9%) women, of whom 388 (20.1%) had psychotic disorders and 1543 (79.9%) had non-psychotic disorders. Psychotic symptoms were assessed using the PRIME Screen-Revised (PS-R) questionnaire. The cohort was grouped according to gender, age (adolescents ≤ 21 years, adults > 21 years), and clinical diagnosis. Within the full sample, gender differences in psychotic symptoms were not significant, except that females appeared to have more severe symptoms of disorganized communication than males. However, gender differences began to appear at subgroup levels, after stratification by age and diagnosis. Female adolescents reported more severe psychotic symptoms than male adolescents, especially in the symptom of perceptual abnormalities, which refer to hallucinations. Different patterns and predictors were found to significantly discriminate between psychotic and non-psychotic disorders among age and gender groups. Our study highlights gender differences in the severity, frequency, and pattern of self-reported psychotic symptoms when screening in a first help-seeking population. Therefore, gender differences should be considered during psychotic symptoms screening.