The impact of REM sleep loss on human brain connectivity.

Brain function is vulnerable to the consequences of inadequate sleep, an adverse trend that is increasingly prevalent. The REM sleep phase has been implicated in coordinating various brain structures and is hypothesized to have potential links to brain variability. However, traditional imaging research have encountered challenges in attributing specific brain region activity to REM sleep, remained understudied at the whole-brain connectivity level. Through the spilt-night paradigm, distinct patterns of REM sleep phases were observed among the full-night sleep group (n = 36), the early-night deprivation group (n = 41), and the late-night deprivation group (n = 36). We employed connectome-based predictive modeling (CPM) to delineate the effects of REM sleep deprivation on the functional connectivity of the brain (REM connectome) during its resting state. The REM sleep-brain connectome was characterized by stronger connectivity within the default mode network (DMN) and between the DMN and visual networks, while fewer predictive edges were observed. Notably, connections such as those between the cingulo-opercular network (CON) and the auditory network, as well as between the subcortex and visual networks, also made significant contributions. These findings elucidate the neural signatures of REM sleep loss and reveal common connectivity patterns across individuals, validated at the group level.

High frequency deep brain stimulation of the dorsal raphe nucleus prevents methamphetamine priming-induced reinstatement of drug seeking in rats.

Drug addiction represents a multifaceted and recurrent brain disorder that possesses the capability to create persistent and ineradicable pathological memory. Deep brain stimulation (DBS) has shown a therapeutic potential for neuropsychological disorders, while the precise stimulation targets and therapeutic parameters for addiction remain deficient. Among the crucial brain regions implicated in drug addiction, the dorsal raphe nucleus (DRN) has been found to exert an essential role in the manifestation of addiction memory. Thus, we investigated the effects of DRN DBS in the treatment of addiction and whether it might produce side effects by a series of behavioral assessments, including methamphetamine priming-induced reinstatement of drug seeking behaviors, food-induced conditioned place preference (CPP), open field test and elevated plus-maze test, and examined brain activity and connectivity after DBS of DRN. We found that high-frequency DBS of the DRN significantly lowered the CPP scores and the number of active-nosepokes in the methamphetamine-primed CPP test and the self-administration model. Moreover, both high-frequency and sham DBS group rats were able to establish significant food-induced place preference, and no significant difference was observed in the open field test and in the elevated plus-maze test between the two groups. Immunofluorescence staining and functional magnetic resonance imaging revealed that high-frequency DBS of the DRN could alter the activity and functional connectivity of brain regions related to addiction. These results indicate that high-frequency DBS of the DRN effectively inhibits methamphetamine priming-induced relapse and seeking behaviors in rats and provides a new target for the treatment of drug addiction.

Memory consolidation drives the enhancement of remote cocaine memory via prefrontal circuit.

Remote memory usually decreases over time, whereas remote drug-cue associated memory exhibits enhancement, increasing the risk of relapse during abstinence. Memory system consolidation is a prerequisite for remote memory formation, but neurobiological underpinnings of the role of consolidation in the enhancement of remote drug memory are unclear. Here, we found that remote cocaine-cue associated memory was enhanced in rats that underwent self-administration training, together with a progressive increase in the response of prelimbic cortex (PrL) CaMKII neurons to cues. System consolidation was required for the enhancement of remote cocaine memory through PrL CaMKII neurons during the early period post-training. Furthermore, dendritic spine maturation in the PrL relied on the basolateral amygdala (BLA) input during the early period of consolidation, contributing to remote memory enhancement. These findings indicate that memory consolidation drives the enhancement of remote cocaine memory through a time-dependent increase in activity and maturation of PrL CaMKII neurons receiving a sustained BLA input.

Association between alcohol consumption and sleep traits: observational and mendelian randomization studies in the UK biobank.

Previous studies have shown that excessive alcohol consumption is associated with poor sleep. However, the health risks of light-to-moderate alcohol consumption in relation to sleep traits (e.g., insomnia, snoring, sleep duration and chronotype) remain undefined, and their causality is still unclear in the general population. To identify the association between alcohol consumption and multiple sleep traits using an observational and Mendelian randomization (MR) design. Observational analyses and one-sample MR (linear and nonlinear) were performed using clinical and individual-level genetic data from the UK Biobank (UKB). Two-sample MR was assessed using summary data from genome-wide association studies from the UKB and other external consortia. Phenotype analyses were externally validated using data from the National Health and Nutrition Examination Survey (2017-2018). Data analysis was conducted from January 2022 to October 2022. The association between alcohol consumption and six self-reported sleep traits (short sleep duration, long sleep duration, chronotype, snoring, waking up in the morning, and insomnia) were analysed. This study included 383,357 UKB participants (mean [SD] age, 57.0 [8.0] years; 46% male) who consumed a mean (SD) of 9.0 (10.0) standard drinks (one standard drink equivalent to 14 g of alcohol) per week. In the observational analyses, alcohol consumption was significantly associated with all sleep traits. Light-moderate-heavy alcohol consumption was linearly linked to snoring and the evening chronotype but nonlinearly associated with insomnia, sleep duration, and napping. In linear MR analyses, a 1-SD (14 g) increase in genetically predicted alcohol consumption was associated with a 1.14-fold (95% CI, 1.07-1.22) higher risk of snoring (P < 0.001), a 1.28-fold (95% CI, 1.20-1.37) higher risk of evening chronotype (P < 0.001) and a 1.24-fold (95% CI, 1.13-1.36) higher risk of difficulty waking up in the morning (P < 0.001). Nonlinear MR analyses did not reveal significant results after Bonferroni adjustment. The results of the two-sample MR analyses were consistent with those of the one-sample MR analyses, but with a slightly attenuated overall estimate. Our findings suggest that even low levels of alcohol consumption may affect sleep health, particularly by increasing the risk of snoring and evening chronotypes. The negative effects of alcohol consumption on sleep should be made clear to the public in order to promote public health.

The combined effects of arteriosclerosis and diabetes on cardiovascular disease risk.

The morbidity and mortality of cardiovascular disease (CVD) rank first among common diseases. Arteriosclerosis and diabetes are risk factors for CVDs, which influence each other. However, their combined effects on CVDs are still unclear. In this study, people who participated in brachial-ankle pulse wave velocity (baPWV) testing and the annual physical examination of the Kailuan Group Finance Co., Ltd., from January 1, 2010, to December 31, 2020, were selected, and their anthropometric, biochemical and epidemiological data were collected. The participants were divided into four groups according to diabetes and arteriosclerosis diagnosis and follow-up. Cox proportional hazards regression and subdistribution hazard models were used to analyse the combined effects of arteriosclerosis and diabetes on CVDs. Multiple sensitivity analyses were also performed. A total of 59,268 Asian populations were selected, including 14,425 females (28.11%) with an average age of 48.10 (± 12.72) years. During follow-up, 1830 subjects developed CVDs (mean follow-up period, 4.72 years). The cumulative incidence rates of the healthy control, diabetes, arteriosclerosis, and comorbidity groups were 5.04% (807/38781), 15.17% (253/3860), 17.04% (465/5987), and 25.59% (305/2684), respectively. The results of multivariate Cox regression analysis showed that compared with the healthy control group, the risk of CVD in the diabetes, arteriosclerosis, and comorbidity groups was significantly increased. Their HR values were 1.88 (95% CI 1.62-2.18), 1.40 (95% CI 1.23-1.60), and 2.10 (95% CI 1.80-2.45), respectively. The results of the sensitivity analysis were robust. For each one standard increase in fasting blood glucose or baPWV, the HR values for CVDs were 1.16 (95% CI 1.12-1.20) and 1.22 (95% CI 1.16-1.28), respectively. The results indicated that both arteriosclerosis and diabetes lead to an increased risk of CVDs. The risk of CVDs, coronary atherosclerotic heart disease, heart failure, stroke, coronary artery bypass grafting and ischemic stroke in patients with arteriosclerosis and diabetes was significantly higher than that in patients with arteriosclerosis or diabetes alone. Therefore, the primary prevention of CVDs in patients with arteriosclerosis complicated with diabetes needs more attention.

Gut-derived bacterial LPS attenuates incubation of methamphetamine craving via modulating microglia.

BACKGROUND: The microbiota-gut-brain axis plays a critical role in the pathophysiology of neuropsychiatric disorders, and the compositions of gut microbiota are altered by addictive drugs. However, the role of gut microbiota in the incubation of methamphetamine (METH) craving remains poorly understood. METHODS: 16S rRNA gene sequencing was performed to assess the richness and diversity of gut microbiota in METH self-administration model. Hematoxylin and eosin staining was performed to evaluate the integrity of intestinal barrier. Immunofluorescence and three-dimensional reconstruction were performed to assess the morphologic changes of microglia. Serum levels of lipopolysaccharide (LPS) were determined using the rat enzyme-linked immunosorbent assay kits. Quantitative real-time PCR was performed to assess transcript levels of dopamine receptor, glutamate ionotropic AMPA receptor 3 and brain-derived neurotrophic factor. RESULTS: METH self-administration induced gut microbiota dysbiosis, intestinal barrier damage and microglia activation in the nucleus accumbens core (NAcc), which was partially recovered after prolonged withdrawal. Microbiota depletion via antibiotic treatment increased LPS levels and induced a marked change in the microglial morphology in the NAcc, as indicated by the decreases in the lengths and numbers of microglial branches. Depleting the gut microbiota also prevented the incubation of METH craving and increased the population of Klebsiella oxytoca. Furthermore, Klebsiella oxytoca treatment or exogenous administration of the gram-negative bacterial cell wall component LPS increased serum and central LPS levels, induced microglial morphological changes and reduced the dopamine receptor transcription in the NAcc. Both treatments and NAcc microinjections of gut-derived bacterial LPS significantly decreased METH craving after prolonged withdrawal. CONCLUSIONS: These data suggest that LPS from gut gram-negative bacteria may enter circulating blood, activate microglia in the brain and consequently decrease METH craving after withdrawal, which may have important implications for novel strategies to prevent METH addiction and relapse.

[Appropriate Use and Abuse of Sedative-Hypnotic Drugs].

The incidence of insomnia has been increasing in recent years. In addition, due to the impact of the COVID-19 pandemic, more and more people are experiencing a variety of insomniac problems, including having difficulty in sleep initation, waking up too early, and short sleep duration. Chronic insomnia may seriously affect patients' life and work, increase their risks of developing physical and mental illnesses, and cause crushing social and economic burdens. Sedative-hypnotics, including benzodiazepine agonists, melatonin receptor agonists, orexin receptor antagonists, and antidepressants with hypnotic effects, are widely used to treat most patients suffering from insomnia. However, there is the phenomenon of the non-medical use and abuse of sedative-hypnotic drugs, especially benzodiazepine receptor agonists. The abuse of sedative-hypnotic drugs may lead to mental and physical dependence, cognitive impairment, depression and anxiety, as well as an increased risks of falls and death. Therefore, drug regulatory authorities in China and other countries have issued relevant policies to reinforce regulation. Herein, we reviewed the prevalent use and safety of sedative-hypnotic drugs and proposed suggestions concerning their appropriate use. Both the efficacy and safety of sedative-hypnotic drugs should be carefully considered so that patients suffering from insomnia receive thorough and prompt treatment and the problem of potential abuse of sedative-hypnotic drugs is assessed in an objective and scientific manner. We also hope to provide references for the standardized clinical use of insomnia drugs.

The phenotype and prediction of long-term physical, mental and cognitive COVID-19 sequelae 20 months after recovery, a community-based cohort study in China.

Long-term sequelae clustering phenotypes are important for precise health care management in COVID-19 survivors. We reported findings for 1000 survivors 20 months after diagnosis of COVID-19 in a community-based cohort in China. Sequelae symptoms were collected from a validated questionnaire covering 27 symptoms involved in five organ systems including self-reported physical condition, dyspnea, cognitive function and mental health. The generalized symptoms were reported with the highest rate (60.7%), followed by the mental (48.3%), cardiopulmonary (39.8%), neurological (37.1%; cognitive impairment, 15.6%), and digestive symptoms (19.1%). Four clusters were identified by latent class analysis: 44.9% no or mild group (cluster 1), 29.2% moderate group with mainly physical impairment (cluster 2), 9.6% moderate group with mainly cognitive and mental health impairment (cluster 3), and 16.3% severe group (cluster 4). Physical comorbidities or history of mental disorders, longer hospitalization periods and severe acute illness predicted severe group. For moderate group, adults less than 60 years, with physical comorbidities and severe acute illness were more likely to have physical symptoms, while adult women with longer hospitalization stays had increased risk of cognitive and mental health impairment. Overall, among more than half of community COVID-19 survivors who presented moderate or severe sequelae 20 months after recovery, three-tenth had physical vulnerability that may require physical therapy aiming to improve functioning, one-tenth mental or cognitive vulnerable cases need psychotherapy and cognitive rehabilitation, and one-sixth severe group needs multidisciplinary clinical management. The remaining half is free to clinical intervention. Our findings introduced an important framework to map numerous symptoms to precise classification of the clinical sequelae phenotype and provide information to guide future stratified recovery interventions.

An orbitofrontal cortex-anterior insular cortex circuit gates compulsive cocaine use.

Compulsive drug use, a cardinal symptom of drug addiction, is characterized by persistent substance use despite adverse consequences. However, little is known about the neural circuit mechanisms behind this behavior. Using a footshock-punished cocaine self-administration procedure, we found individual variability of rats in the process of drug addiction, and rats with compulsive cocaine use presented increased neural activity of the anterior insular cortex (aIC) compared with noncompulsive rats. Chemogenetic manipulating activity of aIC neurons, especially aIC glutamatergic neurons, bidirectionally regulated compulsive cocaine intake. Furthermore, the aIC received inputs from the orbitofrontal cortex (OFC), and the OFC-aIC circuit was enhanced in rats with compulsive cocaine use. Suppression of the OFC-aIC circuit switched rats from punishment resistance to sensitivity, while potentiation of this circuit increased compulsive cocaine use. In conclusion, our results found that aIC glutamatergic neurons and the OFC-aIC circuit gated the shift from controlled to compulsive cocaine use, which could serve as potential therapeutic targets for drug addiction.

Novel role of AMPK in cocaine reinforcement via regulating CRTC1.

Repeated cocaine exposure causes compensatory neuroadaptations in neurons in the nucleus accumbens (NAc), a region that mediates reinforcing effects of drugs. Previous studies suggested a role for adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor, in modulating neuronal morphology and membrane excitability. However, the potential involvement of AMPK in cocaine use disorder is still unclear. The present study employed a cocaine self-administration model in rats to investigate the effect of AMPK and its target cyclic adenosine monophosphate response element binding protein-regulated transcriptional co-activator 1 (CRTC1) on cocaine reinforcement and the motivation for cocaine. We found that intravenous cocaine self-administration significantly decreased AMPK activity in the NAc shell (NAcsh), which persisted for at least 7 days of withdrawal. Cocaine reinforcement, reflected by self-administration behavior, was significantly prevented or enhanced by augmenting or suppressing AMPK activity pharmacologically and genetically, respectively. No difference in sucrose self-administration behavior was found after the same manipulations. The inhibition of AMPK activity in the NAcsh also increased the motivation for cocaine in progressive-ratio schedules of reinforcement, whereas the activation of AMPK had no effect. The knockdown of CRTC1 in the NAcsh significantly impaired cocaine reinforcement, which was rescued by pharmacologically increasing AMPK activity. Altogether, these results indicate that AMPK in the NAcsh is critical for cocaine reinforcement, possibly via the regulation of CRTC1 signaling. These findings may help reveal potential therapeutic targets and have important implications for the treatment of cocaine use disorder and relapse.

The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study.

BACKGROUND: Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that has been developed and demonstrated its effectiveness in decreasing relapse to cocaine and heroin in preclinical models. However, utilizations of abused drugs as the US to initiate MRUP can be problematic. We therefore designed a translational rat study and human study to evaluate the efficacy of a novel methadone-initiated MRUP. METHODS: In the rodent study, male rats underwent heroin self-administration training for 10 consecutive days, and were randomly assigned to receive saline or methadone at 10 min, 1 h or 6 h before extinction training after 28-day withdrawal. The primary outcome was operant heroin seeking after reinstatement. In the human experimental study, male OUD patients were randomly assigned to get MRUP at 10 min or 6 h after methadone or methadone alone. The primary outcomes included experimental cue-induced heroin craving change, sustained abstinence and retention in the study at post intervention and the 5 monthly follow-up assessments. The secondary outcomes were changes in physiological responses including experimental cue-induced blood pressure and heart rate. FINDINGS: Methadone exposure but not saline exposure at 10 min or 1 h before extinction decreased heroin-induced reinstatement of heroin seeking after 28-day of withdrawal in rats (F (8,80) = 8.26, p < 0.001). In the human study, when the MRUP was performed 10 min, but not 6 h after methadone dosing, the MRUP promoted sustained abstinence from heroin throughout 5 monthly follow-up assessments compared to giving methadone alone without MRUP (Hazard Ratio [95%CI] of 0.43 [0.22, 0.83], p = 0.01). The MRUP at 10 min, but not at 6 h after dosing also decreased experimental cue-induced heroin craving and blood pressure increases during the 6-month study duration (group × months × cue types, F (12, 63·3) = 2.41, p = 0.01). INTERPRETATION: The approach of MRUP within about 1 to 6 h after a methadone dose potently improved several key outcomes of OUD patients during methadone maintenance treatment, and could be a potentially novel treatment to prevent opioid relapse. FUNDING: National Natural Science Foundation of China (NO. U1802283, 81761128036, 82001400, 82001404 and 31671143) and Chinese National Programs for Brain Science and Brain-like Intelligence Technology (NO. 2021ZD0200800).

Connectome-based predictive modelling of smoking severity in smokers.

The functional connectivity within and between networks could provide a framework to characterize the neurobiological mechanism of nicotine addiction. This study examined the brain regions that were functionally connected in response to smoking cues and established the brain-behaviour relationships in smokers. Sixty-seven male smokers were enrolled and scanned while performing the cue-reactivity and Stroop task. A whole-brain analysis approach, connectome-based predictive modelling (CPM), was conducted on the data from the cue-reactivity task to identify the networks that could predict the smoking severity with the Shen atlas as templates. Then, the brain-behaviour relationships were verified in a different brain state (Stroop task). CPM identified the smoking severity-related network, as indicated by a significant correlation between predicted and actual smoking severity scores (r = 0.31, p = 0.02). Identified networks mainly involved the canonical networks implicated in the reward process (motor/sensory network and salience network) and executive control (frontoparietal network). Network strength in the Stroop task marginally significantly predicted smoking severity scores (r = 0.23, p = 0.06), partially replicating the brain-behaviour relationship. The CPM results identified the whole-brain neural network related to smoking severity, which was cross-validated by the AAL and Shen atlas. These findings contribute to more profound insights into neural substrates underlying the smoking severity.

Identification of Functional CircRNA-miRNA-mRNA Regulatory Network in Dorsolateral Prefrontal Cortex Neurons of Patients With Cocaine Use Disorder.

Increasing evidence has indicated that circular RNAs (circRNAs) act as competing endogenous RNAs (ceRNAs) regulatory network to regulate the expression of target genes by sponging microRNAs (miRNAs), and therefore play an essential role in many neuropsychiatric disorders, including cocaine use disorder. However, the functional roles and regulatory mechanisms of circRNAs as ceRNAs in dorsolateral prefrontal cortex (dlPFC) of patients with cocaine use disorder remain to be determined. In this study, an expression profiling for dlPFC in 19 patients with cocaine use disorder and 17 controls from Gene Expression Omnibus datasets was used for the differentially expressed circRNAs analysis and the differentially expressed mRNAs analysis. Several tools were used to predict the miRNAs targeted by the circRNAs and the miRNAs targeted mRNAs, which then overlapped with the cocaine-associated differentially expressed mRNAs to determine the functional roles of circRNAs. Functional analysis for the obtained mRNAs was performed via Gene Ontology (GO) in Metascape database. Integrated bioinformatics analysis was conducted to further characterize the circRNA-miRNA-mRNA regulatory network and identify the functions of distinct circRNAs. We found a total of 41 differentially expressed circRNAs, and 98 miRNAs were targeted by these circRNAs. The overlapped mRNAs targeted by the miRNAs and the differentially expressed mRNAs constructed a circRNA-miRNA-mRNA regulation network including 24 circRNAs, 43 miRNAs, and 82 mRNAs in the dlPFC of patients with cocaine use disorder. Functional analysis indicated the regulation network mainly participated in cell response-related, receptor signaling-related, protein modification-related and axonogenesis-related pathways, which might be involved with cocaine use disorder. Additionally, we determined four hub genes (HSP90AA1, HSPA1B, YWHAG, and RAB8A) from the protein-protein interaction network and constructed a circRNA-miRNA-hub gene subnetwork based on the four hub genes. In conclusion, our findings provide a deeper understanding of the circRNAs-related ceRNAs regulatory mechanisms in the pathogenesis of cocaine use disorder.

Neurocan regulates vulnerability to stress and the anti-depressant effect of ketamine in adolescent rats.

Depression is more prevalent among adolescents than adults, but the underlying mechanisms remain largely unknown. Using a subthreshold chronic stress model, here we show that developmentally regulated expressions of the perineuronal nets (PNNs), and one of the components, Neurocan in the prelimbic cortex (PrL) are important for the vulnerability to stress and depressive-like behaviors in both adolescent and adult rats. Reduction of PNNs or Neurocan with pharmacological or viral methods to mimic the expression of PNNs in the PrL during adolescence compromised resilience to stress in adult rats, while virally mediated overexpression of Neurocan reversed vulnerability to stress in adolescent rats. Ketamine, a recent-approved drug for treatment-resistant depression rescued impaired function of Parvalbumin-positive neurons function, increased expression of PNNs in the PrL, and reversed depressive-like behaviors in adolescent rats. Furthermore, we show that Neurocan mediates the anti-depressant effect of ketamine, virally mediated reduction of Neurocan in the PrL abolished the anti-depressant effect of ketamine in adolescent rats. Our findings show an important role of Neurocan in depression in adolescence, and suggest a novel mechanism for the anti-depressant effect of ketamine.

COVID-19 Induced Economic Slowdown and Mental Health Issues.

The COVID-19 pandemic has pressed a pause button on global economic development, and induced significant mental health problems. In order to demonstrate the progressed relationship between the pandemic, economic slowdown, and mental health burden, we overviewed the global-level gross domestic product changes and mental problems variation since the outbreak of COVID-19, and reviewed comprehensively the specific sectors influenced by the pandemic, including international trade, worldwide travel, education system, healthcare system, and individual employment. We hope to provide timely evidence to help with the promotion of policymakers' effective strategies in mitigating economic losses induced by the pandemic; we suggest different governments or policy makers in different countries to share information and experience in dealing with COVID-19-induced economic slowdown and promote COVID-19 vaccine popularization plan to protect every individual worldwide against the coronavirus essentially; and we appeal international information share and collaboration to minimize stigmatization related to adverse mental consequences of COVID-19 and to increase mental health wellbeings of people all over the world.

Global prevalence of digital addiction in general population: A systematic review and meta-analysis.

The present meta-analytic review aimed to synthesize the global prevalence characteristics of digital addiction in the general population. We searched PubMed, Embase, Cochrane Library, and PsycINFO for studies reporting prevalence of various subtypes of digital addiction published before October 31, 2021. Studies were eligible if they were published in peer-reviewed journals, used a validated tool to assess digital addiction, and passed the qualify assessment. In total, 498 articles with 507 studies were included in systematic review, and the meta-analysis included 495 articles with 504 studies covering 2,123,762 individuals from 64 countries. Global pooled prevalence estimates were 26.99% (95% CI, 22.73-31.73) for smartphone addiction, 17.42% (95% CI, 12.42-23.89) for social media addiction, 14.22% (95% CI, 12.90-15.65) for Internet addiction, 8.23% (95% CI, 5.75-11.66) for cybersex addiction, and 6.04% (95% CI, 4.80-7.57) for game addiction. Higher prevalence of digital addiction was found in Eastern Mediterranean region and low/lower-middle income countries. Males had higher risk for Internet and game addiction. An increasing trend of digital addiction during the past two decades was found, which dramatically worsened during COVID-19 pandemic. This study provides the first and comprehensive estimation for the global prevalence of multiple subtypes of digital addiction, which varied between regions, economic levels, time periods of publication, genders, and assessment scales. PROSPERO ID: CRD42020171117.

A systematic review and meta-analysis on the prevalence of stigma in infectious diseases, including COVID-19: a call to action.

Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.

Comparing three extinction methods to reduce fear expression and generalization.

Fear extinction is easy to achieve but difficult to maintain, as evidenced by the relapse of fear after extinction. Counterconditioning and novelty-facilitated extinction have been shown to interfere with fear expression without erasing it. Because of the similarity between the two extinction paradigms, we extended the standard extinction, which merely omitted the expected threat outcomes after exposure to original threat cues. The modified paradigm provided a stimulus (neutral picture or positive picture) to replace the omitted threat outcomes during extinction. Sixty-four healthy volunteers were randomized into three groups for a three-day procedure: fear acquisition (day 1), fear extinction (day 2), and fear recall and generalization test (day 3). Our results showed the modified extinction paradigm failed to prevent fear expression in spontaneous recovery and reinstatement tests. However, novelty-facilitated extinction showed powerful effects in preventing fear generalization. Besides, there was a negative correlation between spontaneous recovery index and emotion regulation scores. We speculated that emotion and prediction error may be important factors influencing fear extinction and affect fear recall and generalization. Overall, this study suggests that novelty-facilitated extinction had a superior effect in preventing fear generalization, providing new perspectives for enhancing the effect of exposure therapy.

Astrocytes: the neglected stars in the central nervous system and drug addiction.

With the advent of improved tools to examine the astrocytes, which have been believed to play a supportive role in the central nervous system (CNS) for years, their participation in the operation of the CNS and drug addiction was unveiled. Assisting the formation and function of the CNS, astrocytes are involved in physiological and pathological brain activities. Drug addiction is a pervasive psychiatric disorder, characterized by compulsive drug-taking behavior and high rate of relapse, impacting individual health and society stability and safety. When exposed to drugs of abuse, astrocytes go through a series of alterations, contributing to the development of addiction. Here we review how astrocytes contribute to the CNS and drug addiction. We hope that understanding the interaction between addictive drugs and astrocytes may help discover new mechanisms underlying the addiction and produce novel therapeutic treatments.

COVID-19 Vaccine-Related Psychological Stress Among General Public in China.

Background: The COVID-19 pandemic is our generation's greatest global challenge to our public health system. Vaccines are considered one of the most effective tools available for preventing COVID-19 infection and its complications and sequelae. Understanding and addressing the psychological stress related to COVID-19 vaccination may promote acceptance of these vaccines. Methods: We conducted an online survey from January 29 to April 26, 2021 to explore stress levels related to COVID-19 vaccination among the general public in China. Participants were asked to evaluate their psychological stress of considering whether or not to get vaccinated at the beginning period of the COVID-19 mass vaccination, after getting access to the information about the vaccine, as well as after getting vaccinated, using visual analog stress scale. Multiple linear regression analysis was performed to explore factors potentially associated with COVID-19-related psychological stress levels before and after getting vaccinated. Results: A total of 34,041 participants were included in the final analysis. The mean stress score concerning COVID-19 vaccination was 3.90 ± 2.60 among all participants, and significantly decreased over time. In addition, the vaccine-related stress level significantly decreased after accessing information about the COVID-19 vaccine (N = 29,396), as well as after getting vaccinated (N = 5,103). Multivariable regression analysis showed higher stress levels related to COVID-19 vaccination in participants who were younger, having lower education level, having history of chronic diseases, mistrusting vaccine's efficacy, experience of vaccine allergy events, being affected by the COVID-19 epidemic, and having mental illness symptoms. Moreover, mistrust in vaccine efficacy and experience of vaccine allergy events had a long-term impact on psychological stress levels about COVID-19 vaccination even after getting vaccinated. Conclusions: The current findings profiled the COVID-19 vaccine-related psychological stress among the general public in China. Population-specific management and interventions targeting the stress related to COVID-19 vaccination are needed to help governments and policy makers promote individual's willingness to get vaccinations for public well-being during the COVID-19 pandemic.