Cognitive impairment in adolescent and adult-onset psychosis: a comparative study.

BACKGROUND: Cognitive impairment presents in both adolescent-onset(ado-OP) and adult-onset psychosis(adu-OP). Age and neurodevelopmental factors likely contribute to cognitive differences. This study aimed to characterize cognitive functions in ado-OP compared to adu-OP in a clinical population with drug-naive first-episode psychosis(FEP). METHODS: A total of 788 drug-naive patients with FEP and 774 sex- and age-matched healthy controls(HCs) were included. Participants were divided into four groups by whether they were under or over 21 years of age: adolescent-onset FEP(ado-FEP, n = 380), adult-onset FEP(adu-FEP, n = 408), adolescent HC(ado-HC, n = 334), and adult HC(adu-HC, n = 440). Comprehensive cognitive assessments were performed using the MATRICS Cognitive Consensus Battery(MCCB), covers six cognitive domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning, and problem-solving. Data analyses were conducted using correlation analyses and binary logistic regression. RESULTS: The patterns of cognitive domain differences between ado-FEP and adu-FEP were found to be similar to those between ado-HC and adu-HC, whereas cognitive impairments appeared to be more pronounced in patients with adu-OP than ado-OP. The mazes subtest had the maximum effect size(ES) in the FEP(ES = 0.37) and HC(ES = 0.30) groups when comparing the adolescent and adult groups. Cognitive subtests were mostly significantly correlated with negative symptoms, especially for adolescents with FEP, in which all the subtests were significantly correlated with negative symptoms in the ado-FEP group. Better performance in the domains of spatial cognition and problem-solving abilities was more likely in the ado-FEP group than in the adu-FEP group. CONCLUSIONS: These findings suggest cognitive differences between adolescents and adults but similar patterns of affected domains in HCs and patients with FEP. Therefore, the development of targeted cognitive interventions tailored to the specific needs of different age groups appears warranted.

Enhanced energy conservation and response accuracy of a pneumatic control system.

The energy consumption of pneumatic systems is occupying an increasingly considerable proportion in the industrial systems. However, due to the response characteristics of actuators, the pneumatic control system generally has a low energy utilization efficiency. How to improve the response accuracy of the pneumatic system while reducing energy consumption remains a key problem to be solved. In this paper, a three-voltage acceleration waveform and its generation method are proposed, and the acceleration circuit is designed. A multi-mode acceleration switching strategy and backstepping sliding mode controller (BSMC) are applied. The test results show that compared to the traditional methods, BSMC respectively saves 26.27% of the air consumption, as well as 32.35% of the valve group power consumption. It also achieves the lowest root-mean-square error (RMSE), of 4.8421 kPa. All the experiments prove that the controller proposed can effectively improve the energy utilization efficiency while maintaining high tracking precision.

Design and evaluation of a drug-in-adhesive patch for the transdermal delivery of ketoprofen.

The purpose of this study was to design a drug-in-adhesive (DIA) patch for transdermal delivery of ketoprofen, using hot-melt pressure-sensitive adhesive as the matrix of the patch. The adhesion properties and skin permeation of the patches were examined, and in vivo pharmacokinetics and tissue distribution of patches were evaluated. The novel ketoprofen patch with high adhesion was prepared by holt-melt method. The effects of different percentages of L-menthol on in vitro permeation were screened, 3% was added as the amount of permeation enhancer and the 24 h cumulative permeation amount(277.46 ± 15.58 µg/cm2) comparable to that of commercial patch MOHRUS®(279.74 ± 29.23 µg/cm2). Pharmacokinetic and the tissue distribution study showed no matter in plasma, muscle or skin, the drug concentration of self-made ketoprofen patch was equivalent to that of commercial patch. These data indicated that the self-made patch provided a new reference for the development of ketoprofen dosage forms and promising alternative strategy for analgesic treatment.

mRNA 5-methylcytosine in Eimeria tenella oocysts: An abundant post-transcriptional modification associated with broad-ranging biological processes.

Eimeria tenella is the major causative agent of chicken coccidiosis. 5-Methylcytosine (m5C) is a type of RNA chemical modifications reported to regulate diverse biological processes. However, the distribution and biological functions of m5C in E. tenella mRNAs are yet to be known. Herein, we report transcriptome-wide profiling of mRNA m5C in E. tenella by employing m5C RNA immunoprecipitation followed by a deep-sequencing approach (m5C-RIP-seq). Our data showed that m5C peaks were distributed across the whole mRNA body. Compared with unsporulated oocysts, there were 2813 hypermethylated and 1850 hypomethylated m5C peaks in sporulated oocysts. Generally, a positive correlation between m5C modification and gene expression levels was observed. The mRNA sequencing (RNA-seq) and m5C-RIP-seq data were consistent with the results of the quantitative reverse transcription PCR (RT-qPCR) and methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR), respectively. Gene Ontology (GO) and pathway enrichment analysis predicated diverse biological functions and pathways, including microtubule motor activity, helicase activity, cGMP-PKG signaling pathway, aminoacyl-tRNA biosynthesis, glycolysis/gluconeogenesis, and spliceosome. Meanwhile, stage-specific gene expression signatures of m5C-related regulators were observed. Altogether, our findings reveal the transcriptional significance of m5C modification in E. tenella oocysts, providing resources and clues for further in-depth research.

Simultaneous quantification of icaritin and its novel 3-methylcarbamate prodrug in rat plasma using HPLC-MS/MS and its application to pharmacokinetic study.

A sensitive, rapid, and simple HPLC-MS/MS method was first developed and fully validated to determine the icaritin (ICT) and its novel 3-methylcarbamate prodrug (3N) simultaneously in rat plasma. Analytes were extracted from rat plasma using a liquid-liquid extraction (LLE) method. Chromatographic separation was performed on ACE Excel 2 C18-Amide column. Quantitation of analytes was conducted on an LCMS-8060 triple-quadrupole tandem mass spectrometer. The quantitation mode was the multiple reaction monitoring via positive electrospray ionization. The calibration curve was linear over the concentration range of 1 to 200 ng/ml for ICT with a correlation coefficient of r = 0.9950 and 1 to 400 ng/ml for 3N with a correlation coefficient of r = 0.9956. The intra-precision RSDs were ≤12% for ICT and 3N. The inter-day precision RSDs were ≤10% for ICT and 3N. The accuracy RE was between -2.6% and 7.8% for ICT and 3N. The average ICT, 3N and IS recoveries were 87.9%, 83.6%, and 84.3%. The plasma matrix of ICT and 3N complied with the guidelines. ICT and 3N were stable in rat plasma under various tested conditions. This work has been successfully applied to studying the pharmacokinetics of ICT and 3N.

Revealing the impact of modified modules flexibility on gemcitabine prodrug nanoassemblies for effective cancer therapy.

Prodrug nanoassemblies combine the advantages of prodrug strategies and nanotechnology have been widely utilized for delivering antitumor drugs. These prodrugs typically comprise active drug modules, response modules, and modification modules. Among them, the modification modules play a critical factor in improving the self-assembly ability of the parent drug. However, the impact of the specific structure of the modification modules on prodrug self-assembly remains elusive. In this study, two gemcitabine (GEM) prodrugs are developed using 2-octyl-1-dodecanol (OD) as flexible modification modules and cholesterol (CLS) as rigid modification modules. Interestingly, the differences in the chemical structure of modification modules significantly affect the assembly performance, drug release, cytotoxicity, tumor accumulation, and antitumor efficacy of prodrug nanoassemblies. It is noteworthy that the prodrug nanoassemblies constructed with flexible modifying chains (OD) exhibit improved stability, faster drug release, and enhanced antitumor effects. Our findings elucidate the significant impact of modification modules on the construction of prodrug nanoassemblies.

Does Electroencephalography Seizure Duration Account for an Adequate Treatment of Magnetic Seizure Therapy for Schizophrenia?

OBJECTIVES: A seizure lasting >15 s has been considered to indicate treatment for magnetic seizure therapy (MST), a modification of electroconvulsive therapy (ECT), without much validation. This study aimed to investigate whether this seizure duration was suitable for the treatment of schizophrenia. METHODS: Altogether, 34 and 33 in-patients with schizophrenia received 10 sessions of MST and ECT, respectively. Clinical symptoms were assessed using the Positive and Negative Symptom Scale at baseline and at the 4-week follow-up. Electroencephalogram (EEG) was monitored during each MST or ECT treatment using bifrontal electrodes. RESULTS: The proportion of participants who achieved the 15-second threshold was only 28.6% in the MST group, with a significant difference between responders and nonresponders. For patients receiving MST, the average EEG seizure duration correlated with the percentage of Positive and Negative Symptom Scale reduction (t(32) = 2.51, P = 0.017, uncorrected; t(32) = 2.00, P = 0.055, corrected with clinical characteristics). The average EEG seizure duration predicted the clinical response at a trend level (Z = 1.76, P = 0.078) with an optimal cutoff of 11.3 seconds. All patients in the ECT group achieved the 15-second threshold. However, their average EEG seizure duration was uncorrelated with clinical improvement. CONCLUSIONS: The duration of EEG seizures may be associated with the antipsychotic effects of MST. This association may have been influenced by various clinical and technical factors. More research is needed to define the specific criteria for adequate MST in schizophrenia in order to achieve personalized dosing.

EMS: A Large-Scale Eye Movement Dataset, Benchmark, and New Model for Schizophrenia Recognition.

Schizophrenia (SZ) is a common and disabling mental illness, and most patients encounter cognitive deficits. The eye-tracking technology has been increasingly used to characterize cognitive deficits for its reasonable time and economic costs. However, there is no large-scale and publicly available eye movement dataset and benchmark for SZ recognition. To address these issues, we release a large-scale Eye Movement dataset for SZ recognition (EMS), which consists of eye movement data from 104 schizophrenics and 104 healthy controls (HCs) based on the free-viewing paradigm with 100 stimuli. We also conduct the first comprehensive benchmark, which has been absent for a long time in this field, to compare the related 13 psychosis recognition methods using six metrics. Besides, we propose a novel mean-shift-based network (MSNet) for eye movement-based SZ recognition, which elaborately combines the mean shift algorithm with convolution to extract the cluster center as the subject feature. In MSNet, first, a stimulus feature branch (SFB) is adopted to enhance each stimulus feature with similar information from all stimulus features, and then, the cluster center branch (CCB) is utilized to generate the cluster center as subject feature and update it by the mean shift vector. The performance of our MSNet is superior to prior contenders, thus, it can act as a powerful baseline to advance subsequent study. To pave the road in this research field, the EMS dataset, the benchmark results, and the code of MSNet are publicly available at https://github.com/YingjieSong1/EMS.

Impaired 40-Hz and intact hierarchical organization mode of auditory steady-state responses among individuals with clinical high-risk for psychosis.

BACKGROUND: Impaired gamma band oscillation, specifically 40-Hz auditory steady state response (ASSR) has been robustly found in schizophrenia, while there is relatively little evidence characterizing the ASSR before full-blown psychosis. OBJECTIVE: To characterize gamma-band ASSR in populations at clinical high-risk for psychosis (CHR). METHODS: One hundred and seven CHR subjects and sixty-five healthy control (HC) subjects were included and completed clinical assessments, the ASSR paradigm of electroencephalography (EEG) and cognitive assessments. Both indices of event-related spectrum perturbation (ERSP) and intertrial coherence (ITC) in response to 20-Hz, 30-Hz and 40-Hz click sounds were respectively qualified and compared between these two groups, as well as the relationship to clinical psychopathology and cognitive function was assessed. RESULTS: At 40-Hz click sounds, ERSP in HC group (1.042 ± 0.047) was statistical significantly increased than that in CHR group (0.873 ± 0.036) (p = 0.005)；at 30-Hz, ERSP in HC group (0.536 ± 0.024) was increased than that in CHR group (0.483 ± 0.019), but the difference was trend statistical significance (p = 0.083)；at 20-Hz, ERSP in HC group (0.452 ± 0.017) was not different significantly from CHR group (0.418 ± 0.013) (p = 0.104). ERSP of the HC group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of the three ERSP showed statistical significance (30-Hz vs. 40-Hz: p < 0.001; 20-Hz vs. 40-Hz: p < 0.001；20-Hz vs. 30-Hz: p = 0.003). Similarly, ERSP of the CHR group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of these three ERSP showed statistical significance (30-Hz vs. 40-Hz: p < 0.001; 20-Hz vs. 40-Hz: p < 0.001；20-Hz vs. 30-Hz: p = 0.002). A statistically significant small positive correlation of 40-Hz ERSP with signal processing speed score was observed in the HC group (ρ = 0.27, p = 0.029). A statistically significant small negative correlation of 40-Hz ERSP with visual learning score was observed in the CHR group (ρ = -0.22, p = 0.023). CONCLUSION: Impaired 40-Hz but undamaged hierarchical organization mode of auditory steady state presented in the CHR populations. Abnormal 40 Hz ASSR for CHR might be associated with cognitive functions, such as information processing speed and visual memory.

Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm.

Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal 'trajectory' of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

Attenuated frontotemporal brain activation during cognitive tasks is associated with lower succinate dehydrogenase protein levels in patients with major depressive disorder.

BACKGROUND: Previous studies have shown a lower hemodynamic response in patients with major depressive disorder (MDD) during cognitive tasks. However, the mechanism underlying impaired hemodynamic and neural responses to cognitive tasks in MDD patients remains unclear. Succinate dehydrogenase (SDH) is a key biomarker of mitochondrial energy generation, and it can affect the hemodynamic response via the neurovascular coupling effect. In the current study, cerebral hemodynamic responses were detected during verbal fluency tasks (VFTs) via functional near-infrared spectroscopy (fNIRS) and SDH protein levels were examined in serum from MDD patients to quickly identify whether these hemodynamic alterations were related to mitochondrial energy metabolism. METHODS: Fifty patients with first-episode drug-naïve MDD and 42 healthy controls (HCs) were recruited according to inclusion and exclusion criteria. The 17-item Hamilton Depression Rating Scale (17-HDRS), Hamilton Anxiety Rating Scale (HAMA) and Inventory of Depressive Symptomatology-Self Report (IDS-SR) were used to assess the clinical symptoms of the patients. All participants underwent fNIRS measurements to evaluate cerebral hemodynamic responses in the frontal and temporal cortex during VFTs; moreover, SDH protein levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Activation in the frontal-temporal brain region during the VFTs was lower in patients with MDD than in HCs. The SDH level in the serum of MDD patients was also significantly lower than that in HCs (p = 0.003), which significantly affected right lateral frontal (p = 0.025) and right temporal (p = 0.022) lobe activation. Both attenuated frontal-temporal activation during the VFTs (OR = 1.531) and lower SDH levels (OR = 1.038) were risk factors for MDD. CONCLUSIONS: MDD patients had lower cerebral hemodynamic responses to VFTs; this was associated with mitochondrial dysfunction, as indicated by SDH protein levels. Furthermore, attenuated hemodynamic responses in frontotemporal regions and lower SDH levels increased the risk for MDD. LIMITATIONS: The sample size is relatively small. SDH protein levels in peripheral blood may not necessarily reflect mitochondrial energy generation in the central nervous system.

Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

Design, synthesis and evaluation of carbamate-bridged amino acid prodrugs of cycloicaritin with improved antitumor activity, aqueous solubility and phase II metabolic stability.

Cycloicaritin (CICT), a bioactive flavonoid derived from the genus Epimedium, exhibits a variety of beneficial biological activities, including promising anticancer effects. However, its poor oral bioavailability is attributed to its extremely low aqueous solubility and rapid elimination via phase II conjugative metabolism. To overcome these limitations, we designed and synthesized a series of carbamate-bridged prodrugs, protecting the hydroxyl group at the 3-position of cycloicaritin by binding with the N-terminus of a natural amino acid. The optimal prodrug 4b demonstrated a significant increase in aqueous solubility as compared to CICT, as well as improved stability in phase II metabolism, while allowing for a rapid release of CICT in the blood upon gastrointestinal absorption. The prodrug 4b also facilitated oral absorption through organic anion-transporting polypeptide 2B1-mediated transport and exhibited moderate cytotoxicity. Importantly, the prodrug enhanced the oral bioavailability of CICT and displayed dose-dependent antitumor activity with superior safety. In summary, the prodrug 4b is a novel potential antitumor drug candidate, and the carbamate-bridged amino acid prodrug approach is a promising strategy for the oral delivery of CICT.

Distribution of self-reported borderline personality disorder traits symptoms in a large-scale clinical population.

Introduction: Borderline Personality Disorder (BPD) traits play a crucial role in the prognosis of psychiatric disorders, as well as in assessing risks associated with negativity and impulsivity. However, there is a lack of data regarding the distribution characteristics of BPD traits and symptoms within clinical populations. Methods: A total of 3015 participants (1321 males, 1694 females) were consecutively sampled from outpatients at the psychiatric and psycho-counseling clinics at the Shanghai Mental Health Center. BPD symptoms were assessed using a self-reported personality diagnostic questionnaire. Having BPD traits is defined as having five or more positive items in self-reported BPD characteristics. Participants were stratified into male and female groups, age groups, and diagnostic groups (schizophrenia, mood disorders, anxiety disorders). Exploratory factor analysis using principal components analysis was conducted. Three factors were identified: "F1: Affective Instability and Impulsivity", "F2: Interpersonal Unstable and Extreme Reactions", and "F3: Identity Disturbance". Results: Among 3015 participants, 45.9% of the patients self-reported BPD traits. Comparing of male and female patients, there was no statistically significant difference in the occurrence rate of BPD traits (χ2 = 1.835, p=0.176). However, in terms of symptoms, female patients reported more symptoms than male patients. Female patients also exhibited more pronounced features on F2 compared to male patients (t =-1.972, p=0.049). There is a general decrease in BPD traits, symptoms, and factors with increasing age. Specifically, the proportion of positive BPD traits is approximately halved before the age of 30 and decreases to around one-third after the age of 30. BPD traits were most common in the Mood Disorders group at 55.7%, followed by the Anxiety Disorders group at 44.4%, and Schizophrenia group at 41.5% (χ2 = 38.084, p<0.001). Discussion: Our study revealed the pervasive presence of BPD traits and symptoms among psychiatric outpatients, exhibiting distinctive distributions across gender, age, and diagnostic categories. These findings emphasize the significance of identifying and addressing BPD pathology in the clinical care of psychiatric outpatients.

Structural and functional abnormalities across clinical stages of psychosis: A multimodal neuroimaging investigation.

BACKGROUND: Structural and functional neurobiological abnormalities have been observed in schizophrenia. Previous studies have concentrated on specific illness stages, obscuring relationships between functional/structural changes and disorder progression. The present study aimed to quantify structural and functional abnormalities across different clinical stages using functional near-infrared spectroscopy (fNIRS) and structural magnetic resonance imaging (sMRI). METHODS: Fifty-four participants with first-episode schizophrenia (FES), 120 with clinically high risk of psychosis (CHR), and 111 healthy controls (HCs) underwent functional near-infrared spectroscopy (fNIRS) to measure oxyhemoglobin (Oxy-Hb) during the verbal fluency task. Among them, 28FES, 64CHR and 55HC also finished sMRI. Oxy-Hb and gray matter volume (GMV) were compared among the three groups while controlling for covariates, including age, sex, years of education, and task performance. Mediation analysis was utilized to determine the mediating effect of GMV on Oxy-Hb and cognition. RESULTS: Compared with the HC group, CHR and FES groups showed significantly reduced brain activity. However, there were no significant differences between the FES and CHR. Pronounced GMV increase in the right frontal pole area (F = 4.234, p = 0.016) was identified in the CHR and FES groups. Mediation analysis showed a significant mediation effect of the right frontal pole GMV between Channel 31 Oxy-Hb and processing speed (z = 2.105, p = 0.035) and attention/vigilance (z = 1.992, p = 0.046). CONCLUSIONS: Brain activation and anatomical deficits were observed in different brain regions, suggesting that anatomical and functional abnormalities are dissociated in the early stages of psychosis. The relationship between neural activity and anatomy may reflect a specific pathophysiology related to cognitive deterioration in schizophrenia.

Timeframe for Conversion to Psychosis From Individuals at Clinical High-Risk: A Quantile Regression.

BACKGROUND AND HYPOTHESIS: The time taken for an individual who is at the clinical high-risk (CHR) stage to transition to full-blown psychosis may vary from months to years. This temporal aspect, known as the timeframe for conversion to psychosis (TCP), is a crucial but relatively underexplored dimension of psychosis development. STUDY DESIGN: The sample consisted of 145 individuals with CHR who completed a 5-year follow-up with a confirmed transition to psychosis within this period. Clinical variables along with functional variables such as the Global Assessment of Function (GAF) score at baseline (GAF baseline) and GAF-drop from the highest score in the past year. The TCP was defined as the duration from CHR identification to psychosis conversion. Participants were categorized into 3 groups based on TCP: "short" (≤6 months, ≤33.3%), "median" (7-17 months, 33.3%-66.6%), and "long" (≥18 months, ≥66.6%). The quantile regression analysis was applied. STUDY RESULTS: The overall sample had a median TCP of 11 months. Significant differences among the three TCP groups were observed, particularly in GAF-drop (χ2 = 8.806, P = .012), disorganized symptoms (χ2 = 7.071, P = .029), and general symptoms (χ2 = 6.586, P = .037). Greater disorganized symptoms (odds ratio [OR] = 0.824, P = .009) and GAF-drop (OR = 0.867, P = .011) were significantly associated with a shorter TCP, whereas greater general symptoms (OR = 1.198, P = .012) predicted a longer TCP. Quantile regression analysis demonstrated a positive association between TCP and GAF baseline above the 0.7 quantile and a negative association between TCP rank and GAF drop below the 0.5 quantile. CONCLUSIONS: This study underscores the pivotal role of functional characteristics in shaping TCP among individuals with CHR, emphasizing the necessity for a comprehensive consideration of temporal aspects in early prevention efforts.

Research trends and hotspot analysis of age-related hearing loss: A bibliometric analysis from 2019 to 2023.

BACKGROUND: Age-related hearing loss (ARHL) - also termed presbycusis - is prevalent among older adults, leading to a range of issues. Although considerable progress in the understanding of ARHL over the decades, available reports lack data from recent years and do not comprehensively reflect the latest advancements and trends. Therefore, our study sought to assess research hotspots and trends in ARHL over the past 5 years to provide the basis for future research. MATERIALS AND METHODS: The Web of Science Core Collection database was searched and screened from January 1, 2019 to October 21, 2023, according to the inclusion criteria. CiteSpace (5.8.R3), VOSviewer (1.6.19), and Microsoft Excel 2019 were employed for bibliometric analysis and visualization. RESULTS: 3084 articles from 92 countries led by the United States and China were included. There has been a steady upward trend in the number of publications from 2019 to 2023. The most productive institutions, authors, and journals are Johns Hopkins University (n = 113), Lin FR (n = 66), and Ear and Hearing (n = 135), respectively. Trend topic analyses revealed that "cochlear synaptopathy" and "dementia" were the predominant foci. Keywords, including "individuals" and "national health", began to appear. CONCLUSION: Over the past 5 years, the annual number of publications has increased significantly and will continue to do so. Research on the mechanism of ARHL, represented by "oxidative stress", is a continuing focus. Emerging topics such as "individual differences" and "national health" may be potential future hotspots in this field.

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 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.