Study Protocol: Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project.

BACKGROUND: Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different underlying neurobiological deficits and 2) objectively tracking disease trajectory and treatment response. Schizophrenia is often confounded with other psychiatric disorders, especially bipolar disorder, if based on cross-sectional symptoms. Awake and sleep EEG have shown promise in identifying neurophysiological differences as biomarkers for schizophrenia. However, most previous studies, while useful, were conducted in European and American populations, had small sample sizes, and utilized varying analytic methods, limiting comprehensive analyses or generalizability to diverse human populations. Furthermore, the extent to which wake and sleep neurophysiology metrics correlate with each other and with symptom severity or cognitive impairment remains unresolved. Moreover, how these neurophysiological markers compare across psychiatric conditions is not well characterized. The utility of biomarkers in clinical trials and practice would be significantly advanced by well-powered transdiagnostic studies. The Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project aims to address these questions through a large, multi-center cohort study involving East Asian populations. To promote transparency and reproducibility, we describe the protocol for the GRINS project. METHODS: The research procedure consists of an initial screening interview followed by three subsequent sessions: an introductory interview, an evaluation visit, and an overnight neurophysiological recording session. Data from multiple domains, including demographic and clinical characteristics, behavioral performance (cognitive tasks, motor sequence tasks), and neurophysiological metrics (both awake and sleep electroencephalography), are collected by research groups specialized in each domain. CONCLUSION: Pilot results from the GRINS project demonstrate the feasibility of this study protocol and highlight the importance of such research, as well as its potential to study a broader range of patients with psychiatric conditions. Through GRINS, we are generating a valuable dataset across multiple domains to identify neurophysiological markers of schizophrenia individually and in combination. By applying this protocol to related mental disorders often confounded with each other, we can gather information that offers insight into the neurophysiological characteristics and underlying mechanisms of these severe conditions, informing objective diagnosis, stratification for clinical research, and ultimately, the development of better-targeted treatment matching in the clinic.

Smoking may increase the usage of antidepressant: evidence from genomic perspective analysis.

This study uses the two-sample Mendelian randomization (TSMR) method to explore the causal relationships between smoking initiation (SMKI), never smoking (NSMK), past tobacco smoking (PTSMK), and the usage of antidepressants (ATD). Single-nucleotide polymorphisms (SNPs) with genome-wide significance (P < 5E-08) related to SMKI, NSMK, and PTSMK were selected from the genome-wide association study (GWAS) database as instrumental variables (IVs). The main method, inverse variance weighted (IVW), was utilized to investigate the causal relationship. The results demonstrated a positive causal relationship between SMKI and ATD use, where SMKI leads to an increase in ATD use. Conversely, NSMK and PTSMK showed a negative causal relationship with ATD use, meaning that NSMK and PTSMK lead to a reduction in ATD use. Additionally, sensitivity analysis showed that the results of this study were robust and reliable. Using the TSMR method and from a genetic perspective, this study found that SMKI leads to an increase in ATD use, while NSMK and PTSMK reduce ATD use.

Two-Hour Nicotine Withdrawal Improves Inhibitory Control Dysfunction in Male Smokers: Evidence from a Smoking-Cued Go/No-Go Task ERP Study.

Purpose: Nicotine withdrawal is a multifaceted physiological and psychological process that can induce a spectrum of mood disturbances. Gaining a more nuanced understanding of how pure nicotine withdrawal influences cognitive control functions may provide valuable insights for the enhancement of smoking cessation programs. This study investigated changes in inhibitory control function in smokers after 2-hour nicotine withdrawal using the event-related potential (ERP) technique. Participants and Methods: 28 nicotine dependence (ND) patients and 28 health controls (HCs) completed a smoking-cued Go/No-go task containing two different types of picture stimuli, smoking-cued and neutral picture stimuli. We analyzed the behavioral and ERP data using a mixed model Repeated Measure Analysis of Variance (ANOVA). Results: No-go trials accuracy rate (ACC) at baseline (time 1) was lower in the ND group compared to HCs with smoking-cued stimuli, and No-go trials ACC after 2-hour nicotine withdrawal (time 2) was not lower in the ND group compared to HCs. When confronted with smoking-cued stimuli, the No-go trials ACC was higher in time 2 than in time 1 in the ND group. For the ERP component, the No-go N2 amplitudes in the ND group with smoking-cued stimuli were lower than that of HCs, whereas after 2-hour nicotine withdrawal, the ND group's No-go N2 amplitudes higher than that at time 1, and did not differ from that of HCs. No-go P3 amplitudes were not significantly different between the two groups. Conclusion: Evidenced from ERP data, ND patients have an inhibitory control dysfunction in the face of smoking cues, which is mainly manifested in the early stage of response inhibition rather than in the late stage. Two-hour nicotine withdrawal improves inhibitory control dysfunction in ND patients. The No-go N2 component is an important and sensitive neuroelectrophysiological indicator of inhibitory control function in ND patients.

Neural Correlates of Cognitive Dysfunction in Conditional Reasoning in Schizophrenia: An Event-related Potential Study.

Purpose: Schizophrenia patients show impaired conditional reasoning. This study was to investigate event-related potential (ERP) characteristics of the conditional reasoning in schizophrenia. Patients and methods: Participants included 24 schizophrenia patients and 30 normal controls (NCs), and the measurements of ERPs were conducted during the Wason selection task. Results: Results showed that NCs consistently outperformed schizophrenia patients in terms of accuracy. Among the different rule types of the task, the precautionary type experiment yielded the highest accuracy rates. In contrast, both the descriptive and abstract type experiments resulted in lower accuracy. The RTs of the abstract type experiment were the shortest among the four experiments. In the abstract type of the Wason selection task, the NCs exhibited higher amplitudes for both the N1 and P2 components compared to the schizophrenia patients. At the parietal lobe, the N2 amplitudes were higher for the social contract type of the task compared to the precautionary version. At the frontal lobe, the N2 amplitudes were highest for the abstract type of the task. In the abstract type, the N2 amplitude at the parietal lobe was higher than that at the central lobe. The NCs displayed lower amplitudes for both the P3 and slow wave compared to the schizophrenia patients. Differences were observed between the NC and schizophrenia groups in terms of the latencies for N1, P2, N2, P3 and slow wave components across different experiment types and regions of interest. Conclusion: In conclusion, the observed ERP patterns provide valuable insights into the neural mechanisms underlying the Wason selection task, highlighting the differences between NCs and patients with schizophrenia.

Mining and analysis of adverse event signals of Cariprazine based on the real-world data of FAERS database.

OBJECTIVE: This study aims to analyze the adverse events (AEs) of Cariprazine based on the FAERS database, providing evidence for its safety surveillance. METHODS: For signal quantification of Cariprazine-related AEs, we used disproportionality analysis including the Ratio of Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS) algorithms. RESULTS: We selected Cariprazine-related AE reports from the FAERS database from the fourth quarter of 2015 to the first quarter of 2023, and performed a detailed data analysis. Out of a total of 12,278,580 case reports, 3659 were found to be directly related to Cariprazine. We identified 140 Preferred Terms (PT) to describe these AEs, finding that they involved 27 organ systems. Specifically, AEs related to eye disorders such as Cataract cortical, Cataract nuclear, Accommodation disorder, Lenticular opacities, Oculogyric crisis, Dyschromatopsia were not explicitly mentioned in the drug's leaflet, indicating the presence of new ADR signals. CONCLUSION: Analysis of the FAERS database identified AEs associated with Cariprazine, notably in eye disorders not previously documented in the drug's official leaflet. These findings emphasize the need for continuous post-market surveillance and awareness among healthcare professionals regarding potential new ADR signals.

Neural Correlates of Anhedonia in Major Depressive Disorder: Insights from Concurrent Analysis of Feedback-Related Negativity and Stimulus-Preceding Negativity.

Purpose: Anhedonia, a core symptom of major depressive disorder (MDD), is explored in this study, focusing on the neural underpinnings through the examination of two event-related potential (ERP) components: feedback-related negativity (FRN) and stimulus-preceding negativity (SPN). Patients and Methods: This cross-sectional study was conducted in China from March 2022 to March 2023. It involved 35 MDD patients and 31 healthy controls (HC) participating in a modified 2-door task with simultaneous EEG recordings. Depression severity and anhedonia were assessed using the Hamilton Depression Scale (HAMD) and the Temporal Experience of Pleasure Scale (TEPS-CV), respectively. FRN and SPN metrics, along with correlations with each other and clinical assessments, were examined. Results: In comparison to the HC group, the MDD group exhibited significantly lower scores in TEPS-CV (t = 2.854, p = 0.006) and its subscales (t = -3.596, p = 0.001 and t = 2.434, p = 0.018, respectively), along with consistently reduced amplitudes of FRN (F 1.64= 4.726, p = 0.033) and SPN (F 1.64= 4.195, p = 0.045) across all conditions. Limited correlations were observed between ERP metrics and clinical indicators, except for positive correlations between FRN amplitudes (loss minus win) and HAMD scores (r = 0.392, p = 0.020), and SPN amplitudes after losing (SPN-L) and TEPS-CV consumption subscale scores (r = 0.357, p = 0.035). Notably, while the HC group displayed no significant FRN-SPN correlations, the MDD group exhibited positive FRN-SPN correlations under distinct conditions (r = 0.376, p = 0.026 and r = 0.355, p = 0.037, respectively). Conclusion: Our data reveal subjective and objective anhedonia in both consumption and anticipation, suggesting a shared impairment in reward feedback processing and anticipatory neural mechanisms in individuals with MDD. These findings deepen our understanding of anhedonia's neural foundations and may guide targeted interventions for this core symptom.

Causal relationship between sex hormone-binding globulin and major depression: A Mendelian randomization study.

OBJECTIVE: This study aimed to explore the causal relationship between sex hormone-binding globulin (SHBG) and major depression using two-sample Mendelian randomization (MR) studies. METHODS: Based on the genome-wide association study (GWAS) summary data of SHBG and major depression in the European population, which included 214,989 female SHBG samples, 185,221 male SHBG samples, and 500,199 major depression samples, we used genetic factors as instrumental variables to conduct two-sample MR analyses. We used methods including inverse variance weighted (IVW), weighted median, weighted mode, and MR Egger to evaluate the bidirectional causal relationship between SHBG and major depression. RESULTS: The results showed that there was a causal relationship between female SHBG and major depression, which was positively correlated. The ORs were 1.056 (95% CI: 1.005-1.109, p = 0.031) for the weighted median and 1.067 (95% CI: 1.012-1.126, p = 0.021) for the weighted mode. There was no significant effect of male SHBG on major depression (p > 0.05), and there was no significant effect of major depression on female SHBG (p > 0.05). Major depression was negatively correlated with male SHBG, indicating that major depression could lead to a decrease in male SHBG. The OR was 0.954 (95% CI: 0.916-0.993, p = 0.023) for IVW. CONCLUSION: Female SHBG was positively correlated with the risk of major depression, however, major depression was found to be negatively correlated with serum SHBG levels in men, indicating that SHBG plays distinct roles in patients with major depression of different genders.

The Neural Correlates of the Social Perception Dysfunction in Schizophrenia: An fMRI Study.

Purpose: Patients with schizophrenia show deficits in facial emotion recognition and emotional intensity assessment, and also exhibit structural and functional irregularities in specific brain regions. In this study, we aimed to examine differences in active brain regions involved in processing the Emotion Intensity Recognition Task (EIRT), which can serve as an indicator of emotion recognition and ability to perceive intensity, between patients with schizophrenia and healthy controls (HCs). The purpose of this study was to investigate dysfunctional brain regions and investigate the role of the amygdala in social cognition deficits in patients with schizophrenia by focusing on alterations in amygdala activity linked to facial emotion recognition. Participants and Methods: Twenty-two patients who met a diagnostic criteria for schizophrenia according to DSM-IV and 27 HCs participated in an MRI scan while completing the EIRT. Behavioral and MRI data were collected and analyzed. Results: Behavioral results showed that patients with schizophrenia made significantly more errors in recognizing surprise, happiness, sadness, fear, and neutral expressions, and patients with schizophrenia exhibited significantly slower response times in recognizing happy facial expressions. Imaging results showed that schizophrenia patients found hypoactivation in several inferior parietal and temporal regions, in the cerebrum and anterior cingulate; and decreased amygdala activation in individuals with schizophrenia was associated with impaired recognition of fear in facial expressions. Conclusion: Facial emotion processing deficits are emotion-specific (surprise, happiness, sadness, fear, and neutral expressions) in schizophrenia. Hypoactivation in several inferior parietal and temporal regions, in the cerebrum and anterior cingulate, was thought to contribute to symptom formation in schizophrenia. Reduction in amygdala activation in schizophrenia patients was associated with impairment of the fear-emotional process.

Hypoconnectivity within the cingulo-opercular network in patients with mild cognitive impairment in Chinese communities.

INTRODUCTION: At rest, the brain's higher cognitive systems engage in correlated activity patterns, forming networks. With mild cognitive impairment (MCI), it is essential to understand how functional connectivity within and between resting-state networks changes. This study used resting-state functional connectivity to identify significant differences within and between the cingulo-opercular network (CON) and default mode network (DMN). METHODS: We assessed cognitive function in patients using the Chinese version of the Alzheimer's disease assessment scale-Cognitive subscale (ADAS-Cog). A group of MCI subjects (ages 60-83 years, n = 45) was compared to age-matched healthy controls (n = 70). Resting-state functional connectivity was used to determine functional connectivity strength within and between the CON and DMN. RESULTS: Compared to healthy controls, the MCI group showed significantly lower functional connectivity within the CON (F = 10.76, df = 1, p = 0.001, FDR adjusted p = 0.003). Additionally, the MCI group displayed no distinct differences in functional connectivity within DMN (F = 0.162, df = 1, p = 0.688, FDR adjusted p = 0.688) and between CON and DMN (F = 2.270, df = 1, p = 0.135, FDR adjusted p = 0.262). Moreover, we found no correlation between ADAS-Cog and within- or between-connectivity metrics among subjects with MCI. CONCLUSIONS: Our findings indicate that specific patterns of hypoconnectivity within CON circuitry may characterize MCI relative to healthy controls. This work improves our understanding of network dysfunction underlying MCI and could inform more targeted treatment.

Causal relationships between dietary habits and five major mental disorders: A two-sample Mendelian randomization study.

OBJECTIVE: To explore the causal relationship between dietary habits and five major mental disorders using the two-sample Mendelian randomization (MR) analysis. METHODS: This study was based on the summary data of the genome-wide association study (GWAS) on diet and five major mental disorders in the European population. The genetic locus data of five major mental disorders (mania, bipolar disorder, manic depression, depression, schizophrenia) from those who never eat eggs, dairy, wheat, and sugar were used. Two-sample MR analysis was conducted to evaluate the causal relationship between diet and five major mental disorders. RESULTS: This study revealed a causal relationship between "Never eat Wheat products" and all five types of mental disorders (mania, bipolar disorder, manic depression, depression, schizophrenia), demonstrating a significant negative correlation (P < 0.05). However, no significant causal relationship was observed between "Never eat Sugar or foods/drinks containing sugar" and any of the five mental disorders (P > 0.05). Furthermore, the study found that the statement "Never eat eggs, dairy, wheat, sugar: I eat all of the above" had a causal relationship with mania, bipolar disorder, and manic depression, showing a significant positive correlation (P < 0.05). However, this statement did not exhibit a significant causal relationship with depression and schizophrenia (P > 0.05). CONCLUSION: There was a negative correlation between never eating wheat products and the five mental disorders (mania, bipolar disorder, manic depression, depression, schizophrenia), indicating that never eating wheat products may reduce the risk of mental disorders.

Decreased beta 1 (12-15 Hertz) power modulates the transfer of suicidal ideation to suicide in major depressive disorder.

BACKGROUND: Suicide prevention for major depressive disorder (MDD) is a worldwide challenge, especially for suicide attempt (SA). Viewing suicide as a state rather than a lifetime event provided new perspectives on suicide research. OBJECTIVE: This study aimed to verify and complement SAs biomarkers of MDD with a recent SA sample. METHODS: This study included 189 participants (60 healthy controls; 47 MDD patients with non-suicide (MDD-NSs), 40 MDD patients with suicide ideation (MDD-SIs) and 42 MDD patients with SA (MDD-SAs)). MDD patients with an acute SA time was determined to be within 1 week since the last SA. SUICIDALITY Part in MINI was applied to evaluate suicidality. Absolute powers in 14 frequency bands were extracted from subject's resting-state electroencephalography data and compared within four groups. The relationship among suicidality, the number of SA and powers in significant frequency bands were investigated. RESULTS: MDD-SIs had increased powers in delta, theta, alpha and beta band on the right frontocentral channels compared to MDD-NSs, while MDD-SAs had decreased powers in delta, beta and gamma bands on widely the right frontocentral and parietooccipital channels compared to MDD-SIs. Beta 1 power was the lowest in MDD-SAs and was modulated by the number of SA. The correlation between suicidality and beta 1 power was negative in MDD-SAs and positive in MDD-SIs. CONCLUSION: Reduced beta 1 (12-15 Hz) power could be essential in promoting suicidal behaviour in MDD. Research on recent SA samples contributes to a better understanding of suicide mechanisms and preventing suicidal behaviour in MDD.

Identification of VIPR2 rare and common variants in the Chinese Han population with schizophrenia.

Introduction: Schizophrenia is a severe and chronic psychiatric disorder with hereditary risk up to 80% as previous studies indicated. Several researches have demonstrated a significant association between schizophrenia and microduplications that overlap the vasoactive intestinal peptide receptor 2 gene (VIPR2). Methods: To further investigate potential causal VIPR2 gene variants, all exons and un-translated portions of the VIPR2 gene were sequenced using amplicon targeted resequencing in 1804 Chinese Han patients with schizophrenia and 996 healthy counterparts in the present study. Results: Nineteen rare non-synonymous mutations and 1 frameshift deletion was identified for schizophrenia, among which 5 variants have never been reported so far. Frequencies of rare non-synonymous mutations were significantly different between the two groups. Specifically, the non-synonymous mutation rs78564798 (Pallele = 0.006) as well as two rare variations in the VIPR2 gene's introns (rs372544903, Pallele = 0.026 and a novel mutation, chr7:159034078, GRCh38, Pallele = 0.048) were significantly associated with schizophrenia. Discussion: Our findings add new evidence that the functional and probable causative variants of VIPR2 gene may play an important role in susceptibility to schizophrenia. Further studies on validations of VIPR2's function in the etiology of schizophrenia are warranted.

The Neural Correlates of the Recognition of Emotional Intensity Deficits in Major Depression: An ERP Study.

Purpose: Deficits in facial emotional intensity recognition have been associated with social cognition in patients with major depression. The study examined multiple event-related potential (ERP) components in patients with major depression and investigated the relationships between ERPs, social cognition, and clinical features. Participants and Methods: Thirty-one patients met DSM-IV diagnosis of depression and 31 healthy participants completed the emotion intensity recognition task (EIRT), while ERPs were recorded. Data on ERP components (P100, N170, P200, and P300) were analyzed. Results: The behavioral results showed that patients with major depression performed worse on EIRT, including all six categories of emotions (sadness, disgust, happiness, surprise, anger, and fear), compared to healthy participants. The ERP results showed that patients with major depression exhibited higher P100 amplitudes for sad and happy faces than healthy participants; P300 amplitudes induced by sad and surprise faces were also higher than in healthy participants, mainly in the central and temporal lobes. A positive correlation was found between sadness intensity scores and P100 amplitudes in patients with major depression. Conclusion: Patients with major depression are biased in their identification of facial expressions indicating emotional intensity. Specifically, they have emotional biases in the early and late stages of cognitive processing, mainly in the form of sensitivity to sad stimuli. It may lead to a persistent rumination of sadness that is detrimental to the remission of depression. Additionally, patients with major depression devote different amounts of cognitive resources for different intensities of sad faces during the preconscious stage of cognitive processing. The more intense their perception of sadness, the more cognitive resources they devote. Therefore, the assessment of the intensity of facial expressions is an important research topic, with clinical implications on social cognitive function in patients with major depression.

Preliminary Analysis of Volume-Based Resting-State Functional MRI Characteristics of Successful Aging in China.

BACKGROUND: Resting-state function MRI (rs-fMRI) research on successful aging can provide insight into the mechanism of aging with a different perspective from aging-related disease. OBJECTIVE: rs-fMRI research was used to analyze the brain function characteristics of successful aging. METHODS: A total of 47 usual aging individuals and 26 successful aging (SA) individuals underwent rs-fMRI scans and neuropsychological tests. Volume-based rs-fMRI data analysis was performed with DPASF to obtain ALFF, ReHo, DC, and VMHC. RESULTS: The SA group showed increased ALFF in right opercular part of inferior frontal gyrus (Frontal_Inf_Oper_R) and right supramarginal gyrus; increased ReHo in right middle temporal pole gyrus and decreased ReHo in left superior frontal gyrus and middle occipital gyrus; increased DC in right medial orbitofrontal gyrus and pulvinar part of thalamus; decreased DC in left fusiform gyrus and right medial frontal gyrus; increased VMHC in right medial orbitofrontal gyrus; and decreased VMHC in the right superior temporal gyrus, right and left middle temporal gyrus, right and left triangular part of inferior frontal gyrus. ALFF in Frontal_Inf_Oper_R were found to be significantly correlated with MMSE scores (r = 0.301, p = 0.014) and ages (r = -0.264, p = 0.032) in all subjects, which could be used to distinguish the SA (AUC = 0.733, 95% CI: 0.604-0.863) by ROC analysis. CONCLUSION: The brain regions with altered fMRI characteristics in SA group were concentrated in frontal (6 brain regions) and temporal (4 brain regions) lobes. ALFF in Frontal_Inf_Oper_R was significantly correlated to cognitive function and ages, which might be used to distinguish the SA.

A spectrum of altered non-rapid eye movement sleep in schizophrenia.

Background: Multiple facets of sleep neurophysiology, including electroencephalography (EEG) metrics such as non-rapid eye movement (NREM) spindles and slow oscillations (SO), are altered in individuals with schizophrenia (SCZ). However, beyond group-level analyses which treat all patients as a unitary set, the extent to which NREM deficits vary among patients is unclear, as are their relationships to other sources of heterogeneity including clinical factors, illness duration and ageing, cognitive profiles and medication regimens. Using newly collected high density sleep EEG data on 103 individuals with SCZ and 68 controls, we first sought to replicate our previously reported (Kozhemiako et. al, 2022) group-level mean differences between patients and controls (original N=130). Then in the combined sample (N=301 including 175 patients), we characterized patient-to-patient variability in NREM neurophysiology. Results: We replicated all group-level mean differences and confirmed the high accuracy of our predictive model (Area Under the ROC Curve, AUC = 0.93 for diagnosis). Compared to controls, patients showed significantly increased between-individual variability across many (26%) sleep metrics, with patterns only partially recapitulating those for group-level mean differences. Although multiple clinical and cognitive factors were associated with NREM metrics including spindle density, collectively they did not account for much of the general increase in patient-to-patient variability. Medication regimen was a greater (albeit still partial) contributor to variability, although original group mean differences persisted after controlling for medications. Some sleep metrics including fast spindle density showed exaggerated age-related effects in SCZ, and patients exhibited older predicted biological ages based on an independent model of ageing and the sleep EEG. Conclusion: We demonstrated robust and replicable alterations in sleep neurophysiology in individuals with SCZ and highlighted distinct patterns of effects contrasting between-group means versus within-group variances. We further documented and controlled for a major effect of medication use, and pointed to greater age-related change in NREM sleep in patients. That increased NREM heterogeneity was not explained by standard clinical or cognitive patient assessments suggests the sleep EEG provides novel, nonredundant information to support the goals of personalized medicine. Collectively, our results point to a spectrum of NREM sleep deficits among SCZ patients that can be measured objectively and at scale, and that may offer a unique window on the etiological and genetic diversity that underlies SCZ risk, treatment response and prognosis.

The Association Between Clozapine Plasma Concentration, CYP2D6 (*10, *2) Polymorphisms and Risk of Adverse Reactions.

Background: The aim of this article was to study the relationships between the risk of adverse reactions, plasma concentration, and cytochrome P450 2D6 rs1065852 (*10) and rs16947 (*2) polymorphisms for clozapine. Methods: The steady-state clozapine plasma concentration of 100 Chinese inpatients with schizophrenia was determined using 2-dimensional liquid chromatography. The polymorphisms of cytochrome P450 2D6 (*10 and *2) were determined using fluorescent in situ hybridization protocols. Results: The decreased percentages of white blood cells and neutrophils and the elevated percentages of creatine kinase, alanine aminotransferase, and aspartate transferase in patients treated with clozapine for 6 months were linearly associated with clozapine plasma concentration. Compared with the corresponding groups, the clozapine plasma concentrations of individuals with the *10TT genotype and individuals with the *2CC genotype were the highest (P < .05). The decreased percentages of white blood cells and neutrophils and elevated percentages of creatine kinase, alanine aminotransferase, and aspartate transferase for patients with the *10TT genotype were significantly higher than those for patients with the *10CC and *10CT genotypes (P < .05). The decreased percentages of white blood cells and neutrophils and increased percentages of creatine kinase, alanine aminotransferase, and aspartate transferase for patients with the *2CC genotype were significantly higher than those of the other groups (P < .05). The therapeutic reference range of clozapine for Chinese patients with schizophrenia was defined as 102.5-483.1 ng/mL. Conclusion: This study demonstrated that the determination of cytochrome P450 2D6 polymorphisms and therapeutic drug monitoring of clozapine might be beneficial for identifying patients with a higher risk of adverse reactions.

Insight into the potential role of ferroptosis in neurodegenerative diseases.

Ferroptosis is a newly discovered way of programmed cell death, mainly caused by the accumulation of iron-dependent lipid peroxides in cells, which is morphologically, biochemically and genetically different from the previously reported apoptosis, necrosis and autophagy. Studies have found that ferroptosis plays a key role in the occurrence and development of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and vascular dementia, which suggest that ferroptosis may be involved in regulating the progression of neurodegenerative diseases. At present, on the underlying mechanism of ferroptosis in neurodegenerative diseases is still unclear, and relevant research is urgently needed to clarify the regulatory mechanism and provide the possibility for the development of agents targeting ferroptosis. This review focused on the regulatory mechanism of ferroptosis and its various effects in neurodegenerative diseases, in order to provide reference for the research on ferroptosis in neurodegenerative diseases.

The neural correlates of interference control dysfunction of working memory in major depressive disorder: An event-related potential study.

Interference control function is a key function in a series of specific functions of working memory (WM), which is usually impaired in patients with major depressive disorder (MDD). Event-related potentials (ERPs) have advantages in exploring the neural processing of interference control and WM impairment, and therefore, it is helpful to further understand the neural mechanism of MDD. In the present study, 44 patients with MDD and 44 age- and sex-matched healthy controls (HCs) were recruited. All participants completed a 4-gradient difficulty Brown-Peterson task (BPT), whose difficulty was manipulated by changing the demand of interspersed distraction tasks. High-density EEG was simultaneously recorded. The hit rate and reaction time (RT) toward the target stimulus as well as the underlying ERP features were analyzed. The results showed that, when compared with HCs, MDD patients had significantly lower hit rates and longer RTs among all four difficulties of BPT. For ERP components, no significant between-group difference was found in either N100 or P200 average amplitudes; however, the centroparietal late positive potential (LPP) amplitude of both MDD group and HC group decreased with the increase of BPT difficulty, despite the pattern of the HC group was relative moderate. For both groups, the LPP amplitude was significantly smaller in high-order difficult BPT tasks than in low-order difficult tasks. Moreover, LPP amplitude in high-order difficult tasks was much smaller in MDD group than that of HC group. Our findings suggest that failure to control interference well may play a critical role in the impairment of WM in patients with MDD, and provided new evidence that the neural correlates of interference control dysfunction of WM in MDD.

Evaluation of depression status and its influencing factors in convalescent elderly patients with first-episode stroke.

OBJECTIVE: To investigate the occurrence and the influencing factors of post-stroke depression (PSD) in first-episode stroke. METHODS: A total of 350 elderly stroke patients who were admitted to Wuxi Central Rehabilitation Hospital for the first time from January 2020 to December 2020 were enrolled in this study. The Hamilton Depression Scale (HAMD) was used to evaluate the depression status of stroke patients. The sociodemographic data, clinical symptoms, social environment and behavioral patterns of the patients were collected to analyze the related factors of depression after stroke through SPSS 20.0 software. RESULTS: The incidence of PSD was 45.71%. There were statistical differences among different gender, lesion nature, lesion location, smoking, hypertension, diabetes, hospitalization enpenses, season of onset, BMI index, NIHSS score, barthel index score, blood pressure variation coefficient and other factors (p = 0.000). Post-stroke depression score was positively correlated with NIHSS score and coefficient of variation of systolic blood pressure (r = 0.935, p = 0.000; r = 0.921, p = 0.000), and negatively correlated with barthel index score (r = -0.964, p = 0.000). Through multivariate Logistic regression analysis, it was found that male (OR=8.624, 95%CI: 5.672-11.715), cerebral infarction (OR=2.561, 95%CI: 1.256-3.567), and the right side lesion (OR=1.933, 95%CI: 1.024-3.026), smoking (OR=2.457, 95%CI: 1.611-3.625), onset in autumn and winter (OR=2.049, 95%CI: 1.201-2.919), high BMI (OR=2.461, 95%CI): 1.426-3.432) were risk factors for depression after stroke, and low SBPV (OR=0.567, 95%CI: 0.352-0.758) and low NISHH score (OR=0.256, 95%CI: 0.105-0.486) were the protective factor for subsequent depression of stroke. CONCLUSION: Males, smoking, patients with onset in autumn and winter, lesions on the right side, high BMI, high NISHH score and high systolic blood pressure variation were closely related to PSD, which should be paid for attention for such patients to prevent the occurrence of PSD and take intervention measures.

Neural correlates of abnormal cognitive conflict resolution in major depression: An event-related potential study.

Abnormal cognitive conflict resolution has been considered as a critical element of executive dysfunctions inpatient with major depression (MD). Further clarifying whether there was a deficit at perceptual encoding stage or the early response-execution stage in conflict control function by event-related potential (ERP) technique in MD would be helpful in understanding the neural mechanism of MD. Participants included twenty-six depressed patients and twenty-six healthy controls (HCs). All participants measured with Hamilton Depression Scale (17-item edition, HAMD) and a Simon task. Electroencephalograms were synchronously recorded when performing the Simon task. The method of residue iteration decomposition was used to analyze the lateralized readiness potential (LRP) and P300 components, which contributed to divides ERP components into a stimulus-locked component (S-cluster), a response-locked component (R-cluster) and an intermediate component cluster (C-cluster) by using latency variability and time markers. Results showed that reactive times (RTs) for both groups were fastest in congruent trials, and slowest in incongruent trials; however, there is no difference in RTs under the three conditions between two groups. Accuracy Rate (ACC) for both groups were the highest in neutral trials, and the lowest in incongruent trials; ACC in MD group were all lower than that of HC group under three conditions. ERP data analyses showed that depressed patients had a deficit in activating the correct response, as reflected by reduced amplitudes of R-LRP, but no abnormality in LRP-S and P300-C. In conclusion, patients with MD present conflict control dysfunction (i.e., abnormal cognitive conflict resolution) at the early response-execution stage, not at perceptual encoding stage, which may be reflected by the reduced R-LRP amplitudes. The abnormal cognitive conflict resolution in activating the correct response might constitute an interesting treatment target.