Cognitive Impairments in Drug-Naive Patients With First-Episode Negative Symptom-Dominant Psychosis.

Importance: Available antipsychotic medications are predominantly used to treat positive symptoms, such as hallucinations and delusions, in patients with first-episode psychosis (FEP). However, treating negative and cognitive symptoms, which are closely related to functional outcomes, remains a challenge. Objective: To explore the cognitive characteristics of patients with negative symptom-dominant (NSD) psychosis. Design, Setting, and Participants: This large-scale cross-sectional study of patients with FEP was led by the Shanghai Mental Health Center in China from 2016 to 2021, with participants recruited from 10 psychiatric tertiary hospitals. A comprehensive cognitive assessment was performed among 788 patients with FEP who were drug-naive. Symptom profiles were determined using the Positive and Negative Symptoms Scale (PANSS), and NSD was defined as a PANSS score for negative symptoms higher than that for positive and general symptoms. Positive symptom-dominant (PSD) and general symptom-dominant (GSD) psychosis were defined similarly. Data were analyzed in 2023. Exposure: Psychotic symptoms were categorized into 3 groups: NSD, PSD, and GSD. Main Outcomes and Measures: Neurocognitive performance, assessed using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. Results: This study included 788 individuals with FEP (median age, 22 [IQR, 17-28] years; 399 men [50.6%]). Patients with NSD exhibited more-pronounced cognitive impairment than did those with PSD or GSD. Specifically, cognitive differences between the NSD and PSD group, as well as between the NSD and GSD group, were most notable in the processing speed and attention domains (Trail Making [F = 4.410; P = .01], Symbol Coding [F = 4.957; P = .007], Verbal Learning [F = 3.198; P = .04], and Continuous Performance [F = 3.057; P = .05]). Patients with PSD and GSD showed no significant cognitive differences. Cognitive impairment was positively associated with the severity of negative symptoms. Most of the cognitive function tests used were able to differentiate patients with NSD from those with PSD and GSD, with significant differences observed across a range of tests, from Brief Visuospatial Memory Test-Revised (χ2 = 3.968; P = .05) to Brief Assessment of Cognition in Schizophrenia symbol coding (χ2 = 9.765; P = .002). Conclusions and Relevance: The findings of this cross-sectional study of patients with FEP suggest the presence of a clinical subtype characterized by a predominance of negative symptoms and cognitive impairment.

Excessive interstitial free-water in cortical gray matter preceding accelerated volume changes in individuals at clinical high risk for psychosis.

Recent studies show that accelerated cortical gray matter (GM) volume reduction seen in anatomical MRI can help distinguish between individuals at clinical high risk (CHR) for psychosis who will develop psychosis and those who will not. This reduction is suggested to represent atypical developmental or degenerative changes accompanying an accumulation of microstructural changes, such as decreased spine density and dendritic arborization. Detecting the microstructural sources of these changes before they accumulate into volume loss is crucial. Our study aimed to detect these microstructural GM alterations using diffusion MRI (dMRI). We tested for baseline and longitudinal group differences in anatomical and dMRI data from 160 individuals at CHR and 96 healthy controls (HC) acquired in a single imaging site. Of the CHR individuals, 33 developed psychosis (CHR-P), while 127 did not (CHR-NP). Among all participants, longitudinal data was available for 45 HCs, 17 CHR-P, and 66 CHR-NP. Eight cortical lobes were examined for GM volume and GM microstructure. A novel dMRI measure, interstitial free water (iFW), was used to quantify GM microstructure by eliminating cerebrospinal fluid contribution. Additionally, we assessed whether these measures differentiated the CHR-P from the CHR-NP. In addition, for completeness, we also investigated changes in cortical thickness and in white matter (WM) microstructure. At baseline the CHR group had significantly higher iFW than HC in the prefrontal, temporal, parietal, and occipital lobes, while volume was reduced only in the temporal lobe. Neither iFW nor volume differentiated between the CHR-P and CHR-NP groups at baseline. However, in many brain areas, the CHR-P group demonstrated significantly accelerated changes (iFW increase and volume reduction) with time than the CHR-NP group. Cortical thickness provided similar results as volume, and there were no significant changes in WM microstructure. Our results demonstrate that microstructural GM changes in individuals at CHR have a wider extent than volumetric changes or microstructural WM changes, and they predate the acceleration of brain changes that occur around psychosis onset. Microstructural GM changes, as reflected by the increased iFW, are thus an early pathology at the prodromal stage of psychosis that may be useful for a better mechanistic understanding of psychosis development.

Cognitive functions following initiation of antipsychotic medication in adolescents and adults at clinical high risk for psychosis: a naturalistic sub group analysis using the MATRICS consensus cognitive battery.

BACKGROUND: The effects of antipsychotic (AP) medications on cognitive functions in individuals at clinical high-risk (CHR) of psychosis are poorly understood. This study compared the effects of AP treatment on cognitive improvement in CHR adolescents and adults. METHODS: A total of 327 CHR participants, with an age range of 13 to 45 years, who underwent baseline neuropsychological assessments and a 1-year clinical follow-up were included. Participants with CHR were categorized into four groups based on their age: adolescents (aged < 18) and adults (aged ≥ 18), as well as their antipsychotic medication status (AP+ or AP-). Therefore, the four groups were defined as Adolescent-AP-, Adolescent-AP+, Adult-AP-, and Adult-AP+. RESULTS: During the follow-up, 231 CHR patients received AP treatment, 94 converted to psychosis, and 161 completed the 1-year follow-up. The Adolescent-AP+ group had more positive symptoms, lower general functions, and cognitive impairments than the Adolescent-AP- group at baseline, but no significant differences were observed among adults. The Adolescent-AP+ group showed a significant increase in the risk of conversion to psychosis (p < 0.001) compared to the Adolescent-AP- group. The Adult-AP+ group showed a decreasing trend in the risk of conversion (p = 0.088) compared to the Adult-AP- group. The Adolescent-AP- group had greater improvement in general functions (p < 0.001), neuropsychological assessment battery mazes (p = 0.025), and brief visuospatial memory test-revised (p = 0.020), as well as a greater decrease in positive symptoms (p < 0.001) at follow-up compared to the Adolescent-AP+ group. No significant differences were observed among adults. CONCLUSIONS: Early use of AP was not associated with a positive effect on cognitive function in CHR adolescents. Instead, the absence of AP treatment was associated with better cognitive recovery, suggesting that AP exposure might not be the preferred choice for cognitive recovery in CHR adolescents, but may be more reasonable for use in adults.

Advancements and Future Directions in Prevention Based on Evaluation for Individuals With Clinical High Risk of Psychosis: Insights From the SHARP Study.

BACKGROUND AND HYPOTHESIS: This review examines the evolution and future prospects of prevention based on evaluation (PBE) for individuals at clinical high risk (CHR) of psychosis, drawing insights from the SHARP (Shanghai At Risk for Psychosis) study. It aims to assess the effectiveness of non-pharmacological interventions in preventing psychosis onset among CHR individuals. STUDY DESIGN: The review provides an overview of the developmental history of the SHARP study and its contributions to understanding the needs of CHR individuals. It explores the limitations of traditional antipsychotic approaches and introduces PBE as a promising framework for intervention. STUDY RESULTS: Three key interventions implemented by the SHARP team are discussed: nutritional supplementation based on niacin skin response blunting, precision transcranial magnetic stimulation targeting cognitive and brain functional abnormalities, and cognitive behavioral therapy for psychotic symptoms addressing symptomatology and impaired insight characteristics. Each intervention is evaluated within the context of PBE, emphasizing the potential for tailored approaches to CHR individuals. CONCLUSIONS: The review highlights the strengths and clinical applications of the discussed interventions, underscoring their potential to revolutionize preventive care for CHR individuals. It also provides insights into future directions for PBE in CHR populations, including efforts to expand evaluation techniques and enhance precision in interventions.

ANP alleviates motion sickness potentially through regulating endolymph volume in the inner ear increased by AVP.

INTRODUCTION: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aims to investigate the anti-motion sickness action and inner ear-related mechanisms of ANP. METHODS: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method. RESULTS: Both rotational stimulus and intraperitoneal AVP injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour, and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in-vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells. CONCLUSION: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.

Development of a tobramycin-loaded calcium alginate microsphere/chitosan composite sponge with antibacterial effects as a wound dressing.

Traditional dressings exhibit several disadvantages, as they frequently lead to bacterial infections, cause severe tissue adhesion and perform a relatively single function. Therefore, in this study, a composite sponge dressing with antibacterial properties and excellent physicochemical properties was developed. Six groups of tobramycin-loaded calcium alginate microspheres were prepared by changing the amount of tobramycin added, and the optimal group was selected. Then, seven groups of tobramycin-loaded calcium alginate microsphere/chitosan composite sponges were fabricated via a solvent blending process and a freeze-drying method. The surface morphology, physicochemical properties, in vitro degradation properties, in vitro drug release properties, antibacterial properties and cytotoxicity of the composite sponges were examined. Group 3.0 contained the best microspheres with the largest drug loading capacity, good swelling performance and cumulative drug release rate, obvious and sustained antibacterial activity, and good cytocompatibility. The tobramycin-loaded calcium alginate microsphere/chitosan composite sponges exhibited three-dimensional porous structures, and their porosity, swelling rate, water absorption and water retention rates and water vapor transmission rate met the standards needed for an ideal dressing. The comprehensive performance of the sponge was best when 20 mg of drug-loaded microspheres was added (i.e., group 20). The cumulative drug release rate of the sponge was 29.67 ± 4.14% at 7 days, the diameters of the inhibition zones against the three bacteria were greater than 15 mm, and L929 cell proliferation was promoted. These results demonstrated that the tobramycin-loaded calcium alginate microsphere/chitosan composite sponge with 20 mg of tobramycin-loaded microspheres shows promise as a dressing for infected wounds.

Prenatal exposure to fenvalerate causes depressive-like behavior in adulthood by inhibiting brain-derived 5-HT synthesis.

The developmental toxicity of fenvalerate, a representative pyrethroid insecticide, is well documented. The present study aimed to explore whether prenatal exposure to fenvalerate causes depression-like behavior in adulthood. Pregnant mice were orally administrated with either corn oil or fenvalerate (2 or 20 mg/kg) during pregnancy. Depressive-like behaviors were assessed by tail suspension test (TST), forced swim test (FST) and sucrose preference test (SPT). Immobility times in TST and FST were increased in offspring whose mothers were exposed to fenvalerate throughout pregnancy. By contrast, sugar preference index, as determined by SPT, was decreased in fenvalerate-exposed offspring. Prefrontal PSD95, a postsynaptic membrane marker, was downregulated in fenvalerate-exposed adulthood offspring. Fenvalerate-induced reduction of prefrontal PSD95 began at GD18 fetal period. Accordingly, prefrontal 5-HT, a neurotransmitter for synaptogenesis, was also reduced in fenvalerate-exposed GD18 fetuses. Tryptophan hydroxylase 2 (TPH2), a key enzyme for 5-HT synthesis, was downregulated in the midbrain of fenvalerate-exposed GD18 fetuses. Additional experiment showed that GRP78 and p-eIF2α, two endoplasmic reticulum stress-related proteins, were increased in the midbrain of fenvalerate-exposed fetal mice. The present results suggest that prenatal exposure to fenvalerate causes depressive-like behavior in adulthood, partially by inhibiting brain-derived 5-HT synthesis.

Sex Differences in Personality Disorder and Childhood Maltreatment of Patients with Schizophrenia.

Introduction: Despite numerous studies investigating personality disorder (PD) and childhood maltreatment (CM) characteristics in individuals with schizophrenia (SZ), there remains a scarcity of research focusing on sex differences in PD and CM within large samples of SZ patients. Methods: A total of 592 participants (257 males, 335 females) were consecutively sampled from patients diagnosed with SZ at the psychiatric and psycho-counseling clinics at Shanghai Mental Health Center. PDs were assessed using a self-reported personality diagnostic questionnaire and a structured clinical interview, while CMs were evaluated using the Chinese version of the Child Trauma Questionnaire Short Form. Results: Male patients exhibited a prominent self-reported trait of antisocial PD (t=1.972, p=0.049), while female patients demonstrated a notable emphasis on histrionic PD traits (t=-2.057, p=0.040). Structured interviews for PD diagnoses further indicated a higher comorbidity of schizotypal (χ2=4.805, p=0.028) and schizoid (χ2=6.957, p=0.008) PDs among male patients compared to female patients. Additionally, male patients reported a higher degree (t=2.957, p=0.003) and proportion (χ2=5.277, p=0.022) of experiences of physical abuse in their self-reported CM. Logistic regression analyses highlight distinct factors: higher antisocial PD traits and physical abuse are associated with male patients, while histrionic PD traits and emotional abuse are associated with female patients. Discussion: These findings underscore the importance of recognizing and addressing sex-specific manifestations of personality pathology and the nuanced impact of CM in the clinical management of individuals with SZ. The study advocates for tailored interventions that consider the distinct needs associated with sex differences in both personality traits and CM experiences among SZ patients.

Childhood maltreatment and personality disorders in adolescents and adults with psychotic or non-psychotic disorders.

Introduction: While the attention to personality disorders (PD) and childhood maltreatment (CM) has grown in recent years, there remains limited understanding of the prevalence and distinctions of PD and CM in clinical populations of Chinese adolescents in comparison to adults. Methods: A total of 1,417 participants were consecutively sampled from patients diagnosed with either psychotic or non-psychotic disorders in the psychiatric and psycho-counseling clinics at Shanghai Mental Health Center. The participants were categorized into two groups based on their age: adolescents (aged 15-21 years) and adults (aged 22-35 years). PDs were evaluated using a self-reported personality diagnostic questionnaire and a structured clinical interview, while CMs were assessed using the Chinese version of the Child Trauma Questionnaire Short Form. Results: When comparing self-reported PD traits and CM between adolescents and adults, differences emerge. Adolescents, particularly in the psychotic disorder group, exhibit more pronounced schizotypal PD traits (p=0.029), and this pattern extends to non-psychotic disorders (p<0.001). Adolescents in the non-psychotic disorder group also report higher levels of emotional abuse (p=0.014), with a notable trend in physical abuse experiences compared to adults (p=0.057). Furthermore, the most prevalent PDs in the clinical sample are avoidant, borderline, and obsessive-compulsive PDs. Among patients with psychotic disorders, adolescents exhibit higher rates of schizoid, schizotypal, and obsessive-compulsive PDs compared to adults. Logistic regression analyses highlight distinct predictors for psychotic and non-psychotic disorders in adolescents and adults. Discussion: The findings emphasize distinct differences in PDs and CMs between adolescent and adult groups, shedding light on their potential roles in psychotic and non-psychotic disorders.

Repetitive transcranial magnetic stimulation can improve negative symptoms and/or neurocognitive impairments in the first psychosis episode: A randomized controlled trial.

OBJECTIVE: Negative symptoms and neurocognitive impairments in psychosis correlate with their severity. Currently, there is no satisfactory treatment. We aimed to evaluate and compare the effects of repetitive transcranial magnetic stimulation(rTMS) on negative symptoms and neurocognitive impairments in patients in first-episode of psychosis(FEP) in a randomized controlled trial(RCT). METHOD: This is a single-site RCT of 85 patients with FEP. Patients were randomized to receive a 4-week course of active(n = 45) or sham rTMS(n = 40). Factor analysis was applied to a cross-sectional dataset of 744 FEP patients who completed negative symptom evaluation and neurocognitive battery tests. Two independent dimensions were generated and used for the K-means cluster analysis to produce sub-clusters. rTMS of 1-Hz was delivered to the right orbitofrontal(OFC) cortex. RESULTS: Two distinct dimensional factors of neurocognitive functions(factor-1) and negative symptoms(factor-2), and three clusters with distinctive features were generated. Significant improvements in factor-1 and factor-2 were observed after 4-weeks of rTMS treatment in both the active and sham rTMS groups. The repeated-measures analysis of variance revealed a significant effect of time×group(F = 5.594, p = 0.021, η2 = 0.073) on factor-2, but no effect of time×group on factor-1. Only improvements in negative symptoms were significantly different between the active and sham rTMS groups(p = 0.028). Patients in cluster-3 characterized by extensive negative symptoms, showed greater improvement in the active rTMS group than in the sham rTMS group. CONCLUSIONS: The 1-Hz right OFC cortex rTMS is more effective in reducing negative symptoms than neurocognitive impairments. It is especially effective in patients with dominantly negative symptoms in FEP.

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.

Bromine atom introduction improves the F- sensing ability of an indolo[3,2-b]carbazole-salicylaldehyde-based fluorescence turn-on sensor.

The heavy-atom effect usually quenches fluorescence, but scarcely enhances it. Herein, fluorescence turn-on sensors without or with a bromine atom for F- detection are presented, achieving fast response time within 1 min, and the LODs of 1.9 × 10-7 and 8.5 × 10-8 M, reflecting that halogen atom introduction is beneficial for F- detection ability improvement. The sensing mechanism of -OH unit deprotonation is confirmed based on the results of a 1 : 2 stoichiometric ratio, 1H NMR titration and TD-DFT calculation. The water environment F- detection and spiked recovery experiments demonstrate their potential for real sample detection.

Association between the MDR1 rs1045642 polymorphism and breast cancer risk: An updated meta­analysis.

Multidrug resistance 1 (MDR1) is a transmembrane transporter on the cell membrane. As an ATP-dependent efflux pump, MDR1 is mainly responsible for the adsorption, distribution, metabolism, excretion and transportation of anticancer drugs to cancer cells. Mutations of the MDR1 gene may be associated with the incidence of cancer. In the past decade, associations found between the MDR1 rs1045642 polymorphism and breast cancer have been inconsistent and inconclusive. Therefore, the present study performed a meta-analysis including studies published up until August 16, 2023 to systematically evaluate the association between the MDR1 rs1045642 polymorphism and breast cancer risk. A total of 21 published case studies involving 6,815 patients with breast cancer and 9,227 healthy participants were included in the meta-analysis. Overall, the MDR1 rs1045642 polymorphism was not significantly associated with breast cancer-associated risk. However, in the subgroup analysis, the MDR1 rs1045642 polymorphism was found to be notably associated with a higher risk of breast cancer among Asian populations in recessive models [TT vs. CT + CC; odds ratio (OR)=1.393; 95% confidence interval (CI), 1.143-1.698; P=0.001; I2<25%]. The MDR1 C3435T polymorphism was also associated with a notable decrease in the incidence of breast cancer in mixed ethnicity populations (TT and CT + CC; OR=0.578; 95% CI, 0.390-0.856; P=0.006; I2<25%). In Caucasian populations, the MDR1 rs1045642 polymorphism was not associated with breast cancer risk. In conclusion, the present meta-analysis demonstrated that the MDR1 rs1045642 polymorphism may increase the risk of breast cancer in Asian populations, is associated with a reduced risk of breast cancer in mixed populations but has no notable effect in Caucasian populations.

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.

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.

Operation-robust SiO2-based memristive application in air.

In recent years, neuromorphic computing is recognized as a promising path to further improve the efficiency of integrated computing system in the post-Moore era, relying on its high parallelism. As a key fundamental element in hardware-implementing neuromorphic system, the synaptic device has made substantial research progress. Among these, SiO2 trapping-based memristive devices generally have systematically integrated merits, such as ease of fabrication and high CMOS process compatibility, but electrochemical activity to oxygen makes them unreliable for operating in air. Here, by using ultrathin Si3N4 as a physical isolation layer, we have obtained a robust memristive device based on SiO2 trapping although operating in air. Further study of Si3N4 thickness dependence has demonstrated that 7 nm is suggested as the most favorable thickness for reliable and flexible programming, and that an inherent isolating mechanism is 'switching-on' for an electron but 'switching-off' for large-sized oxygen molecules. Based on a device with 7 nm Si3N4, we have mimicked various modes of synaptic plasticities. These results could thus not only increase the prospects of using SiO2 trapping in memristive applications but also provide an effective path to improve the robustness of these SiO2-based applications against ambient air.

Expression and clinical significance of miR-141-5p as a biomarker in the serum of patients with early spontaneous abortion.

AIM: miR-141-5p expression in patients with Early Spontaneous Abortion (ESA) and its correlation with hormone levels during pregnancy were investigated. METHODS: A total of 70 pregnant women with ESA were selected as the research group, and 70 normal pregnant women who chose abortion for non-medical reasons were selected as the Con group. Serum ß-HCG, Progesterone (P), and Estrogen (E2) were detected by enzyme-linked immunosorbent assay. Differentially expressed miRNAs were screened by miRNA microarray analysis. miR-141-5p expression was detected by RT-qPCR, and its correlation with serum ß-HCG, P, and E2 levels was analyzed. The diagnostic value of miR-141-5p for ESA was evaluated by the ROC curve. RESULTS: Serum ß-HCG, P, and E2 were decreased and serum miR-141-5p was increased in patients with ESA. Pearson correlation analysis showed that serum ß-HCG, P, and E2 levels were negatively correlated with miR-141-5p expression levels. ROC curve showed that miR-141-5p had a diagnostic value for ESA. CONCLUSIONS: miR-141-5p is related to hormone levels during pregnancy and is expected to become a new candidate diagnostic marker for ESA.

An event-related potential study of prepotent motor activity and response inhibition deficits in schizophrenia.

Response inhibition deficits in schizophrenia (SZ) are accompanied by reduced neural activities using event-related potential (ERP) measurements. However, it remains unclear whether the reduction in inhibition-related ERPs in SZ is contingent upon prepotent motor tendencies. This study aimed to examine the relationship between ERP markers of prepotent motor activity (lateralised readiness potential, LRP) and response inhibition (P3) by collecting behavioural and EEG data from healthy control (HC) subjects and SZ patients during a modified Go/No-Go task. A trial-averaged analysis revealed that SZ patients made more commission errors in No-Go trials compared with HC subjects, although there was no significant difference in the inhibition-related P3 effect (i.e. larger P3 amplitudes in No-Go compared with Go trials) between the two groups. Subsequently, No-Go trials were sorted and median-split into bins of stronger and weaker motor tendencies. Both HC and SZ participants made more commission errors when faced with stronger motor tendencies. The LRP-sorted P3 data indicated that HC subjects exhibited larger P3 effects in response to stronger motor tendencies, whereas this trial-by-trial association between P3 and motor tendencies was absent in SZ patients. Furthermore, SZ patients displayed diminished P3 effects in No-Go trials with stronger motor tendencies but not in trials with weaker motor tendencies, relative to HC subjects. Taken together, these findings suggest that SZ patients are unable to dynamically adjust inhibition-related neural activities in response to changing inhibitory control demands and emphasise the importance of considering prepotent motor activity when investigating the neural mechanisms underlying response inhibition deficits in SZ.

Eye Movement Characteristics for Predicting a Transition to Psychosis: Longitudinal Changes and Implications.

BACKGROUND AND HYPOTHESIS: Substantive inquiry into the predictive power of eye movement (EM) features for clinical high-risk (CHR) conversion and their longitudinal trajectories is currently sparse. This study aimed to investigate the efficiency of machine learning predictive models relying on EM indices and examine the longitudinal alterations of these indices across the temporal continuum. STUDY DESIGN: EM assessments (fixation stability, free-viewing, and smooth pursuit tasks) were performed on 140 CHR and 98 healthy control participants at baseline, followed by a 1-year longitudinal observational study. We adopted Cox regression analysis and constructed random forest prediction models. We also employed linear mixed-effects models (LMMs) to analyze longitudinal changes of indices while stratifying by group and time. STUDY RESULTS: Of the 123 CHR participants who underwent a 1-year clinical follow-up, 25 progressed to full-blown psychosis, while 98 remained non-converters. Compared with the non-converters, the converters exhibited prolonged fixation durations, decreased saccade amplitudes during the free-viewing task; larger saccades, and reduced velocity gain during the smooth pursuit task. Furthermore, based on 4 baseline EM measures, a random forest model classified converters and non-converters with an accuracy of 0.776 (95% CI: 0.633, 0.882). Finally, LMMs demonstrated no significant longitudinal alterations in the aforementioned indices among converters after 1 year. CONCLUSIONS: Aberrant EMs may precede psychosis onset and remain stable after 1 year, and applying eye-tracking technology combined with a modeling approach could potentially aid in predicting CHRs evolution into overt psychosis.

Duration of Untreated Prodromal Psychosis and Cognitive Impairments.

Importance: The possible association between the duration of untreated prodromal symptoms (DUPrS) and cognitive functioning in individuals at clinical high risk (CHR) for psychosis remains underexplored. Objective: To investigate the intricate interplay between DUPrS, cognitive performance, and conversion outcomes, shedding light on the potential role of DUPrS in shaping cognitive trajectories and psychosis risk in individuals at CHR for psychosis. Design, Setting, and Participants: This cohort study of individuals at CHR for psychosis was conducted at the Shanghai Mental Health Center in China from January 10, 2016, to December 29, 2021. Participants at CHR for psychosis typically exhibit attenuated positive symptoms; they were identified according to the Structured Interview for Prodromal Syndromes, underwent baseline neuropsychological assessments, and were evaluated at a 3-year clinical follow-up. Data were analyzed from August 25, 2021, to May 10, 2023. Exposure: Duration of untreated prodromal symptoms and cognitive impairments in individuals at CHR for psychosis. Main Outcomes and Measures: The primary study outcome was conversion to psychosis. The DUPrS was categorized into 3 groups based on percentiles (33rd percentile for short [≤3 months], 34th-66th percentile for median [4-9 months], and 67th-100th percentile for long [≥10 months]). The DUPrS, cognitive variables, and the risk of conversion to psychosis were explored through quantile regression and Cox proportional hazards regression analyses. Results: This study included 506 individuals (median age, 19 [IQR, 16-21] years; 53.6% [n = 271] women). The mean (SD) DUPrS was 7.8 (6.857) months, and the median (IQR) was 6 (3-11) months. The short and median DUPrS groups displayed poorer cognitive performance than the long DUPrS group in the Brief Visuospatial Memory Test-Revised (BVMT-R) (Kruskal-Wallis χ2 = 8.801; P = .01) and Category Fluency Test (CFT) (Kruskal-Wallis χ2 = 6.670; P = .04). Quantile regression analysis revealed positive correlations between DUPrS rank and BVMT-R scores (<90th percentile of DUPrS rank) and CFT scores (within the 20th-70th percentile range of DUPrS rank). Among the 506 participants, 20.8% (95% CI, 17.4%-24.5%) converted to psychosis within 3 years. Cox proportional hazards regression analysis identified lower educational attainment (hazard ratio [HR], 0.912; 95% CI, 0.834-0.998), pronounced negative symptoms (HR, 1.044; 95% CI, 1.005-1.084), and impaired performance on the Neuropsychological Assessment Battery: Mazes (HR, 0.961; 95% CI, 0.924-0.999) and BVMT-R (HR, 0.949; 95% CI, 0.916-0.984) tests as factors associated with conversion. Conclusions and Relevance: The finding of this cohort study suggest the intricate interplay between DUPrS, cognitive performance, and conversion risk in individuals at CHR for psychosis. The findings emphasize the importance of considering both DUPrS and cognitive functioning in assessing the trajectory of these individuals.