OBJECTIVE Social anxiety disorder,also known as social phobia,is the most common of all anxiety disorders.Despite the seriousness of this disorder,it has rarely been studied and as a consequence,little is known about ...OBJECTIVE Social anxiety disorder,also known as social phobia,is the most common of all anxiety disorders.Despite the seriousness of this disorder,it has rarely been studied and as a consequence,little is known about its underlying neurobiology.Growing evidence suggests that inhibitory neurons dysfunction could affect the balance of neuronal activity in psychotic disorders including anxiety,SAD,etc.Ephrin-B(EB) proteins were previously demonstrated to ensure normal distribution and function of inhibitory interneurons in the brain.We thus proposed that deletion of EB2 in inhibitory neurons might destroy the homeostasis of excitatory neurons and inhibitory neurons,and induce behavioral deficits associated with psychotic diseases.METHODS(1)Mice.We generated conditional EB2 knockout mice as a model of SAD and characterized the behaviors and the biochemical changes in the brains of the knockout mice.We also generated a mouse line with a selective deletion of EB2 from vGAT neurons by breeding a v GAT-Cre line with a loxP-flanked alleles in EB2.For EB2 detection,we crossed vGAT-Cre;EphrinB2 loxp/loxp mice with Rosa26-STOP-tdTomato Cre indicator(Ai9) mice to label the vGAT neurons with tdTomato.Mice were maintained in a mixed CD1/129 genetic background.Al experiments involving mice were carried out in accordance with the Shanghai Jiaotong University.Genotypes were unlocked only after completion of analysis.(2) General procedures for behavioral testing.Open field test:Locomotor activity was measured using an open field test.The size of the open field box was 44 cm×44 cm×44 cm.Each mouse was placed in the corner of the open-field apparatus at the beginning of the test,and allowed to explore it for 15 min.The total distance traveled(in cm) and counts for stereotyped behaviors were recorded and analyzed.The total distance traveled was used as an index of locomotor activity.The percentage of center zone entries was considered as anxiety indexes.EPM test:The elevated plus maze apparatus was made of dark gray plastic and comprised two open arms(30 cm×7 cm×0.25 cm) opposed to two enclosed arms(30 cm × 7 cm × 15 cm) elevated60 cm from the floor.Animals were placed in the central area of the apparatus with their head facing an enclosed arm(test duration,5 min).Digitized video recordings with EthoVision software were used for behavioral analysis.The percentage of time spent in open arms and the percentage of open-arm entries were calculated.Social behaviors:Briefly,a top open acrylic box was divided into three compartments by two clear acrylic glass partitions with an opening in the bottom.Wire mesh cages that are either empty or have social stimulus mouse in it were put in the center of each outer compartment.Unfamiliar naive CD1/129 mice of the same age were used as stimulus mice.Prior to the test,the mouse was introduced into the center chamber for 5 min,with both gates closed.Gates were then open and the test mouse was acclimated to explore the empty three-chambered apparatus freely for another 10 min.After the initial 15 min habituation session,mice were placed in the center compartment and allowed to explore freely all the three compartments.To examine the social contact,the following activities were recorded via a video surveillance for 10 min.The number of entries to each compartment,the time spent in each compartment as well as the time and frequency each mouse spent in sniffing were analyzed with EthoVision XT 8.5(Noldus,Wageningen,Netherlands).RESULTS(1)Social preference assays were performed in WT-vGATCre,EB2-flox,and EB2-vGATCre mice respectively.To evaluate social approach behavior,we used a three-chamber social arena to evaluate animals for their social interaction.The control groups of WTvGATCre,EB2-flox mice showed a significant preference for spending time in the social chamber(P<0.05);whereas the EB2-vGATCre mice did not show this preference and spent roughly equal time in the social and nonsocial chambers.(2)To determine if the decrease in social preference could result from changes in locomotion,we compared locomotor activity in EB2-vG ATCre mice and control mice.We did not observe a significant lower locomotive activity in mice.Hence,EB2 deletion caused a change in social preference but not in locomotion.Taken together,EB2 deletion exerts abnormal psychotogenic activity of social deficits which was often considered as an important feature of SAD.(3) The time spent in the open arms is widely used to measure anxiety in mice,with greater time spent in the open arm being considered as less anxious behavior.To normalize for individual differences in overall activity level,the time spent in the open arms was divided by the total time.The ratio was higher for WT-vGATCre mice and EB2-loxp mice as compared to the EB2-vG ATCre mice(P=0.0112,P=0.0197).Thus,results showed that there was a change in anxiety levels from in EB2-vGATCre mice as compared with control mice.CONCLUSION EB2 may be a candidate risk gene for SAD and that the EB2 conditional knockout model could be a tool for studying the underlying mechanisms in SAD.展开更多
Objective To investigate the variations of contingent negative variations(CNV),P_(300)and mismatch negativity(MMN)in depression and anxiety disorders.Methods CNV,P_(300)and MMN were recorded from 44 depressive patient...Objective To investigate the variations of contingent negative variations(CNV),P_(300)and mismatch negativity(MMN)in depression and anxiety disorders.Methods CNV,P_(300)and MMN were recorded from 44 depressive patients using Nicolet Spirit Instrument,and were compared with that of 32 anxiety patients and 28 normal controls(NC).Twenty-one of depressive patients and 18 of anxiety patients were followed up by 2.5 months with the same evoked potentials.Results 1.Compared with NC,all patients in acute episode showed decreased M1 of CNV amplitude,delayed P3 latency and decreased P3 amplitude of Psxo,and delayed MMN latency and decreased MMN amplitude;2.The follow-up study of evoked potentials revealed that abnormal P3 of Psoo and MMN latencies were significant between depressed patients in remission status and NC group but not P3 of P_(300)and MMN amplitudes,and M1 of CNV and P3 of P_(300)amplitudes and P3 of Psoo and MMN latencies are not significant between anxiety patients in remission and NC group.Conclusion Delayed P3 of Psoo and MMN latencies in depression show state and trait markers,while those variations in anxiety correlate with clinical status of anxiety state.展开更多
Objective:The efficacy of monotherapy in alleviating psychological disorders like anxiety and depression among breast cancer patients is suboptimal,necessitating effective psychosocial interventions.Mindfulness-based ...Objective:The efficacy of monotherapy in alleviating psychological disorders like anxiety and depression among breast cancer patients is suboptimal,necessitating effective psychosocial interventions.Mindfulness-based interventions have been shown to mitigate anxiety-depression symptoms and encourage beneficial behaviors.The online mindfulness based cancer recovery(MBCR)offers flexibility and guides practice across various settings,facilitating full patient engagement.This study amis to analyze the impact of a 4-week internet-delivered mindfulness-based cancer recovery program on anxiety,depression,and mindfulness among Chinese patients with breast cancer,and to evaluate the degree of satisfaction breast cancer patients experienced after participating in this program.Methods:This study utilized a two-armed,parallel,randomized controlled trial design.A total of 103 patients with breast cancer from June 2020 to January 2021 in the ward of Breast and Thyroid Surgery of a tertiary hospital in Changsha,Hunan Province were selected and randomly assigned to an intervention group(n=51)and a control group(n=52).The intervention group participated in an internet-delivered mindfulness-based cancer recovery program,which was delivered once a week for 4 weeks.Meanwhile,the control group received weekly group health education for 4 weeks.The outcomes of hospital anxiety and depression scale and mindfulness Attention Awareness Scale were evaluated at 3 distinct time points:Baseline(T1),postintervention(T2),and 1-month follow-up(T3).The satisfaction questionnaire of 4-week mindful cancer rehabilitation training program was used at T2 to evaluate patients’satisfaction with the intervention program.Generalized estimation equations were used to assess differences in anxiety,depression and mindfulness levels between groups before and after the intervention.Results:There were no statistically significant differences in demographic data and outcome index scores between the 2 groups at T1(all P>0.05),indicating that the 2 groups were comparable.The generalized estimating equation analyses showed that the intervention group had significantly better improvement in outcomes compared to the control group,particularly for anxiety(T2β=−1.30,95%CI−1.87 to−0.72;T3β=−2.78,95%CI−3.51 to−2.05)and depression(T2β=−1.92,95%CI−2.78 to−1.06;T3β=−2.96,95%CI−4.05 to−1.87;all P<0.001).Moreover,the mindfulness score in the intervention group was significantly higher than that in the control group at T2(β=3.23,95%CI 0.73 to 5.72)and T3(β=8.06,95%CI 4.37 to 11.75;both P<0.05).In addition,patients in the intervention group were satisfied with the 4-week mindfulness-based cancer recovery intervention and teaching/learning activities used to implement the program.Conclusion:In patients with breast cancer,the 4-week internet-delivered mindfulness based cancer recovery program,as a low-threshold,short-term mental health intervention,has a positive effect on reducing anxiety and depression and improving mindfulness levels.This program holds great promise as a tool for clinical nursing practice,given the high satisfaction and applicability.展开更多
In a recent publication,Hu et al.(2023)have reported that individuals with high trait anxiety exhibit attentional deficits characterized by reduced inhibition of distractors and delayed attentional selection of target...In a recent publication,Hu et al.(2023)have reported that individuals with high trait anxiety exhibit attentional deficits characterized by reduced inhibition of distractors and delayed attentional selection of targets,indicating impaired top-down attentional control.This commentary underscores their significant contributions to the cognitive theory of anxiety.Based on their findings,we propose a novel training approach called attentional inhibition training(AIT),aimed at improving top-down attentional control to alleviate symptoms of anxiety.Furthermore,we explore the potential application of non-invasive transcranial magnetic stimulation(TMS)for rapidly enhancing attentional control function.展开更多
OBJECTIVE To investigate whether electroacupuncture(EA)ameliorates abnormal trigeminal neuralgia(TN)orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1.METHODS A mouse infra...OBJECTIVE To investigate whether electroacupuncture(EA)ameliorates abnormal trigeminal neuralgia(TN)orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1.METHODS A mouse infraorbital nerve transection model(pTION)of neuropathic pain was established,and EA or sham EA was used to treat ipsilateral acu⁃puncture points(GV20-Baihui and ST7-Xia⁃guan).Golgi-Cox staining and transmission elec⁃tron microscopy(TEM)were administrated to observe the changes of synaptic plasticity in the hippocampus CA1.RESULTS Stable and persistent orofacial allodynia and anxiety-like behav⁃iors induced by pT-ION were related to changes in hippocampal synaptic plasticity.Golgi stain⁃ings showed a decrease in the density of dendritic spines,especially mushroom-type dendritic spines,in hippocampal CA1 neurons of pT-ION mice.TEM results showed that the density of synapses,membrane thickness of the postsynaptic density,and length of the synaptic active zone were decreased,whereas the width of the synaptic cleft was increased in pTION mice.EA attenu⁃ated pT-ION-induced orofacial allodynia and anx⁃iety-like behaviors and effectively reversed the abnormal changes in dendritic spines and syn⁃apse of the hippocampal CA1 region.CONCLU⁃SION EA modulates synaptic plasticity of hippo⁃campal CA1 neurons,and reduces abnormal oro⁃facial pain and anxiety-like behavior,providing evidence for a TN treatment strategy.展开更多
OBJECTIVE Na+/K+-ATPase(NKA)is large membrane protein expressed uni⁃versally which is indispensable for the mainte⁃nance of ionic gradient as well as neuronal excit⁃ability.The role of NKA in inflammatory regula⁃tion ...OBJECTIVE Na+/K+-ATPase(NKA)is large membrane protein expressed uni⁃versally which is indispensable for the mainte⁃nance of ionic gradient as well as neuronal excit⁃ability.The role of NKA in inflammatory regula⁃tion is still unclear.Inflammatory responses are initiated upon the activation of inflammasomes.In order to investigate the crosslink between NKA and inflammasome,NKAα1 knockout(KO)N2a cells were generated using CRISPR/Cas9 system.METHODS AND RESULTS qPCR results showed that NLRP1 and NLRP3 were upregulated in response to NKAα1 loss while both NLRC4 and AIM2 remained unaffected.Meanwhile,consistent with the change in NLRP1 and NLRP3,both the mRNA level of ASC and IL-1βwere significantly increased in NKAα1 KO cells.These data indicated that NKAα1 interfer⁃ence might influence the level of NLRP1 and NLRP3 inflammasomes in neuronal cells.Further evidence indicating the potential link between NKA and inflammasome pathway were provided using cytokine array assay where all the differen⁃tiated protein detected were closely linked to NLRP1 and NLRP3.To confirm this effect,we also observed the transcriptional levels of inflam⁃masome proteins in the brain cortex from both NKAα1+/+and NKAα1+/-mice.In line with the observation gained in NKAα1 KO cells,the mRNA level of NLRP1,NLRP3 and IL-1βwere significantly upregulated in NKAα1+/-mice brain.Interestingly,in the primary cultured astrocytes,treatment with LPS/ATP significantly reduced the mRNA and protein levels of NKAα1 expression.These data imply that a negative regulation loop between NKAα1 and inflammation may exist in the central nervous system.Since neuroinflam⁃matory mechanism is currently considered the most potential of interventions to target anxiety,we therefore perform behavioural experiments to investigate the role of NKAα1 in anxiety.Chronic restraint stress(CRS)for 10 d significantly reduced the time and frequency of entering the open arm and prolonged the retention time in the closed arm in the elevated plus-maze test.In the open field test,CRS also reduced both duration and frequency of entering into the central region.Although NKAα1 loss itself did not alter the behaviour performance in the normal condition,it exacerbated CRS-induced above behaviour abnormalities.CONCLUSION NKAα1 is regulat⁃ed upon inflammatory challenger and may be a novel target to treat anxiety.展开更多
Objective:This study aimed to investigate the association of atopic dermatitis(AD)and anxiety/depression behaviors induced by AD with the intestinal microbiota.Additionally,it sought to evaluate the therapeutic potent...Objective:This study aimed to investigate the association of atopic dermatitis(AD)and anxiety/depression behaviors induced by AD with the intestinal microbiota.Additionally,it sought to evaluate the therapeutic potential of mannan oligosaccharide(MOS)in alleviating AD symptoms through the modulation of the gut microbiota and the enhancement of short-chain fatty acids(SCFAs)production.Methods:Female Kunming mice were challenged with 2,4-dinitrofluorobenzene(DNFB)to induce AD-like symptoms.MOS was administered orally daily for 14 days.On the 6th and 11th days post-modeling,the number of scratching bouts in mice was recorded.Following dissection,epidermal thickness,mast cell infiltration,and serum levels of inflammatory cytokines were measured.Meanwhile,cerebral levels of neurotransmitters,including 5-hydroxytryptamine(5-HT)and norepinephrine(NE),were assessed.The abundance of intestinal microbiota and fecal concentrations of SCFAs were also analyzed.Results:MOS significantly reduced AD-like symptoms by reducing inflammatory cytokines,as reflected in a significant decrease in the number of scratching bouts,epidermal thickness,mast cells and inflammatory cytokine levels.MOS intervention up-regulated the expression of 5-HT and NE,and consequently alleviated anxiety and depression-like behaviors.Furthermore,compared with the AD group,MOS intervention increased the gut microbiota abundance of mice,especially beneficial bacteria such as Bifidobacterium,Lactobacillus and Klebsiella.At the same time,these beneficial bacteria significantly increased the fecal contents of SCFAs,especially propionic acid.Correlation analysis indicated that AD amelioration was positively correlated with fecal SCFAs levels and the proliferation of certain intestinal microbes.Conclusion:MOS intervention could offer a novel approach to managing AD and its psychological comorbidities.展开更多
This paper explores the anxiety that students experience in their foreign language learning.It first analyzes correlates of language anxiety,then discusses ways to identify language anxiety,and offers some suggestions...This paper explores the anxiety that students experience in their foreign language learning.It first analyzes correlates of language anxiety,then discusses ways to identify language anxiety,and offers some suggestions for combating language anxiety.展开更多
OBJECTIVE Alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in clinic.Phosphodiesterases(PD...OBJECTIVE Alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in clinic.Phosphodiesterases(PDEs) are a superfamily of enzymes consisting of 11 PDE families that hydrolyze cyclicAMP(cA MP) and/or cyclicGMP(cGMP). Among them,PDE4 is critical in the control of intracellular cAMP levels and has been shown to play an important role in the regulation of ethanol consumption.However,the functional role of PDE4 in mediating alcoholism remains unclear. METHODS Ethanol drinking and preference were examined using the two-bottle choice and/or drinking-in-dark(DID) test in high alcohol preferring(HAP) animals,including C57,HAP,and PDE4-subtype knockout mice,and Fawn-Hooded(FH/Wjd) rats,treated with or without the PDE4 inhibitor rolipram or roflumilast. Ethanol withdrawal-induced anxiety-and depressive-like behaviors were examined using the elevated plusmaze,holeboard,forced-swim,and tail-suspension tests in C57 mice or FH rats in the presence of PDE4 inhibition. Levels of cAMP,CREB were determined in brain regions. RESULTS Treatment with rolipram or roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in C57 and HAP mice as well as FH rats. Mice deficient in PDE4 B,but not PDE4 D,displayed similar effects to general PDE4 inhibition. In addition,rolipram reversed ethanol withdrawal-induced anxietyand depressive-like behaviors 1 d and 14 d,respectively,following withdrawal from ethanol drinking in the two-bottle choice in C57 mice or FH rats. Locomotor activity was not changed in either mice or rats treated with the PDE4 inhibitors. Levels of cAMP,p CREB in the brain were increased by rolipram.CONCLUSION The results provide solid evidence for the important role of PDE4 in ethanol consumptionand ethanol withdrawal-induced symptoms. Inhibitors of PDE4,in particular the PDE4 B isoform,can be a novel class of treatment for alcoholism.展开更多
A high level of public speaking anxiety confronts Chinese advanced learners of English,both in extemporaneous and prepared speeches.The anxiety is caused by reasons found in ESL issues,composition,and delivery.In this...A high level of public speaking anxiety confronts Chinese advanced learners of English,both in extemporaneous and prepared speeches.The anxiety is caused by reasons found in ESL issues,composition,and delivery.In this essay,I will illustrate different forms of speaking anxiety found in Chinese English majors.By presenting the symptoms and analyzing the causes,we shall find that it is a triumvirate of rhetoric composition,delivery,and ESL training that has produced the special anxiety for Chinese English majors.And thus it is only through the combined efforts of the triumvirate that ways of alleviating the anxiety can be found.A suggested course design that encompasses topic selection,content emphasis,progress,and assessment is finally offered.展开更多
In 1995 Ince[1] wrote an article for the Times Higher Educational Supplement noting that there was little theoretical understanding of software engineering and that therefore computer studies did not constitute an aca...In 1995 Ince[1] wrote an article for the Times Higher Educational Supplement noting that there was little theoretical understanding of software engineering and that therefore computer studies did not constitute an academic discipline.Computing departments should be balkanised.Computing staff should be dispersed to other departments such as maths,psychology and business studies.This contro.ersy has recently been rein.igorated by McBride’s article[2] in the same paper and on the British Computer Society web site[3] arguing that in face of the massi.e decline in computing student intake onto uni.ersity undergraduate courses that the future for traditional courses is bleak.The reaction generated[3-4] reflects the anxiety within computing departments.The concern is e.ident.展开更多
OBJECTIVE To investigated the effects of INI-0602 on nociceptive reflex,depression-associated andanxiety-related behaviors caused by neuropathic pain in sciatic nerve injury rats.METHODS Male rat were subjected to sci...OBJECTIVE To investigated the effects of INI-0602 on nociceptive reflex,depression-associated andanxiety-related behaviors caused by neuropathic pain in sciatic nerve injury rats.METHODS Male rat were subjected to sciatic nerve injury(SNI)or sham surgery.Rat received daily treatment with INI-0602 intrathecally,at a dose of 0.25μg/10μL.The response frequency to mechanical allodynia in animals was measured with von Frey hairs on day 1,3,5,7,14,21.Rats were evaluated in the forced swimming test(FST)test,tail suspension test(TST),sucrose preference test(SPT)for depression-like behavior.We performed open field test(OFT)and elevated plus-maze test(EPM)to evaluate anxiety-associated behaviors.Besides,we investigated the alterations of NMDA receptor and the brain-derived neurotrophic factor(BDNF)and also the expression of connexin43 and connexin32,structure protein of gap junction channel,on the protein level and the number of activated astrocyte showed by immunohistochemical.RESULTS The SNI procedure produced mechanical allodynia and accompanied with depressive-like and anxiety-like behavior.Treatment with INI-0602 produced a significant analgesic effect in SNI rats at day 7(model+NS:11.017±1.506 g;model+INI-0602:31.157±1.532 g,P<0.01),and still obviously on the 21th day(31.067±1.787,P<0.01).INI-0602 could also improve the performance of sciatic nerve injury rats among program behavior tests related to depression and anxiety.In parallel with relief of pain,the alterations of NMDA receptor and the brain-derived neurotrophic factor(BDNF),involved in central sensitization and synaptic plasticity,were investigated.INI-0602 not only could inhibited spared nerve injury induced up-regulated of NR2B and phosphorylation NR2B in early and late neuropathic pain(early phase:Nr2b:2.897±0.228,P<0.01;p-Nr2b:2.984±0.236,P<0.01;late phase:Nr2b:2.594±0.187,P<0.01;p-Nr2b:3.124±0.330,P<0.01),but also could inhibit the increased of BDNF in the early(model+NS:3.637±0.381,model+INI-0602:1.148±0.372,P<0.01)and upregulate the BDNF in late stage(model+NS:0.438±0.103,model+INI-0602:1.222±0.092,P<0.01).Meanwhile,INI-0602 significantly decreased the expression of connexin43 and connexin32,structure protein of gap junction channel,on the protein level and the number of activated astrocyte showed by immunohistochemical.CONCLUSION INI-0602 blocked behavioral changes induced by neuropathic pain,suggesting that it might be a promising pharmacological approach of painemotion diseases.展开更多
Objective:Healthcare workers,as a high-stress professional group,face long-term high intensity workloads and complex medical environments,resulting in increasingly prominent mental health issues.In particular,the wide...Objective:Healthcare workers,as a high-stress professional group,face long-term high intensity workloads and complex medical environments,resulting in increasingly prominent mental health issues.In particular,the widespread presence of anxiety symptoms and somatic pain has become a major factor affecting both the quality of care and the career development of healthcare workers.This study aims to investigate the mediating and moderating roles of psychological resilience and sleep in the relationship between somatic pain and anxiety among healthcare workers.Methods:A cross-sectional questionnaire survey was conducted among 1661 healthcare workers.The instruments used included the Generalized Anxiety Disorder-7(GAD-7),item 3 from the Patient Health Questionnaire-9(PHQ-9),the 10-item Connor-Davidson Resilience Scale(CD-RISC-10)for psychological resilience,and the Visual Analogue Scale(VAS)for assessing anxiety,sleep disturbance,psychological resilience,and somatic pain.Results:The detection rate of anxiety symptoms among healthcare workers was 38.95%.Psychological resilience was significantly negatively correlated with anxiety symptoms(r=−0.451,P<0.01),sleep disturbance(r=−0.313,P<0.01),and somatic pain(r=−0.214,P<0.01).Moreover,psychological resilience partially mediated the relationship between somatic pain and anxiety(β=−0.103,P<0.01),and sleep quality moderated the latter part of the mediation model(“somatic pain-psychological resilience-anxiety”).Conclusion:Under high-intensity workloads,healthcare workers generally experience severe anxiety symptoms.Psychological resilience plays an important protective mediating role in their mental health,and sleep quality serves as a moderator in this relationship.Enhancing healthcare workers’psychological resilience and improving their sleep may promote both their physical and mental well-being.展开更多
基金National Natural Science Foundation of China (8150115381571326).
文摘OBJECTIVE Social anxiety disorder,also known as social phobia,is the most common of all anxiety disorders.Despite the seriousness of this disorder,it has rarely been studied and as a consequence,little is known about its underlying neurobiology.Growing evidence suggests that inhibitory neurons dysfunction could affect the balance of neuronal activity in psychotic disorders including anxiety,SAD,etc.Ephrin-B(EB) proteins were previously demonstrated to ensure normal distribution and function of inhibitory interneurons in the brain.We thus proposed that deletion of EB2 in inhibitory neurons might destroy the homeostasis of excitatory neurons and inhibitory neurons,and induce behavioral deficits associated with psychotic diseases.METHODS(1)Mice.We generated conditional EB2 knockout mice as a model of SAD and characterized the behaviors and the biochemical changes in the brains of the knockout mice.We also generated a mouse line with a selective deletion of EB2 from vGAT neurons by breeding a v GAT-Cre line with a loxP-flanked alleles in EB2.For EB2 detection,we crossed vGAT-Cre;EphrinB2 loxp/loxp mice with Rosa26-STOP-tdTomato Cre indicator(Ai9) mice to label the vGAT neurons with tdTomato.Mice were maintained in a mixed CD1/129 genetic background.Al experiments involving mice were carried out in accordance with the Shanghai Jiaotong University.Genotypes were unlocked only after completion of analysis.(2) General procedures for behavioral testing.Open field test:Locomotor activity was measured using an open field test.The size of the open field box was 44 cm×44 cm×44 cm.Each mouse was placed in the corner of the open-field apparatus at the beginning of the test,and allowed to explore it for 15 min.The total distance traveled(in cm) and counts for stereotyped behaviors were recorded and analyzed.The total distance traveled was used as an index of locomotor activity.The percentage of center zone entries was considered as anxiety indexes.EPM test:The elevated plus maze apparatus was made of dark gray plastic and comprised two open arms(30 cm×7 cm×0.25 cm) opposed to two enclosed arms(30 cm × 7 cm × 15 cm) elevated60 cm from the floor.Animals were placed in the central area of the apparatus with their head facing an enclosed arm(test duration,5 min).Digitized video recordings with EthoVision software were used for behavioral analysis.The percentage of time spent in open arms and the percentage of open-arm entries were calculated.Social behaviors:Briefly,a top open acrylic box was divided into three compartments by two clear acrylic glass partitions with an opening in the bottom.Wire mesh cages that are either empty or have social stimulus mouse in it were put in the center of each outer compartment.Unfamiliar naive CD1/129 mice of the same age were used as stimulus mice.Prior to the test,the mouse was introduced into the center chamber for 5 min,with both gates closed.Gates were then open and the test mouse was acclimated to explore the empty three-chambered apparatus freely for another 10 min.After the initial 15 min habituation session,mice were placed in the center compartment and allowed to explore freely all the three compartments.To examine the social contact,the following activities were recorded via a video surveillance for 10 min.The number of entries to each compartment,the time spent in each compartment as well as the time and frequency each mouse spent in sniffing were analyzed with EthoVision XT 8.5(Noldus,Wageningen,Netherlands).RESULTS(1)Social preference assays were performed in WT-vGATCre,EB2-flox,and EB2-vGATCre mice respectively.To evaluate social approach behavior,we used a three-chamber social arena to evaluate animals for their social interaction.The control groups of WTvGATCre,EB2-flox mice showed a significant preference for spending time in the social chamber(P<0.05);whereas the EB2-vGATCre mice did not show this preference and spent roughly equal time in the social and nonsocial chambers.(2)To determine if the decrease in social preference could result from changes in locomotion,we compared locomotor activity in EB2-vG ATCre mice and control mice.We did not observe a significant lower locomotive activity in mice.Hence,EB2 deletion caused a change in social preference but not in locomotion.Taken together,EB2 deletion exerts abnormal psychotogenic activity of social deficits which was often considered as an important feature of SAD.(3) The time spent in the open arms is widely used to measure anxiety in mice,with greater time spent in the open arm being considered as less anxious behavior.To normalize for individual differences in overall activity level,the time spent in the open arms was divided by the total time.The ratio was higher for WT-vGATCre mice and EB2-loxp mice as compared to the EB2-vG ATCre mice(P=0.0112,P=0.0197).Thus,results showed that there was a change in anxiety levels from in EB2-vGATCre mice as compared with control mice.CONCLUSION EB2 may be a candidate risk gene for SAD and that the EB2 conditional knockout model could be a tool for studying the underlying mechanisms in SAD.
文摘Objective To investigate the variations of contingent negative variations(CNV),P_(300)and mismatch negativity(MMN)in depression and anxiety disorders.Methods CNV,P_(300)and MMN were recorded from 44 depressive patients using Nicolet Spirit Instrument,and were compared with that of 32 anxiety patients and 28 normal controls(NC).Twenty-one of depressive patients and 18 of anxiety patients were followed up by 2.5 months with the same evoked potentials.Results 1.Compared with NC,all patients in acute episode showed decreased M1 of CNV amplitude,delayed P3 latency and decreased P3 amplitude of Psxo,and delayed MMN latency and decreased MMN amplitude;2.The follow-up study of evoked potentials revealed that abnormal P3 of Psoo and MMN latencies were significant between depressed patients in remission status and NC group but not P3 of P_(300)and MMN amplitudes,and M1 of CNV and P3 of P_(300)amplitudes and P3 of Psoo and MMN latencies are not significant between anxiety patients in remission and NC group.Conclusion Delayed P3 of Psoo and MMN latencies in depression show state and trait markers,while those variations in anxiety correlate with clinical status of anxiety state.
基金supported by the National Science Fund for Distinguished Young Scholars(81703084)the National Natural Science Foundation of General Program(82272924),and the Hunan Women’s Federation(19WTB03),China.
文摘Objective:The efficacy of monotherapy in alleviating psychological disorders like anxiety and depression among breast cancer patients is suboptimal,necessitating effective psychosocial interventions.Mindfulness-based interventions have been shown to mitigate anxiety-depression symptoms and encourage beneficial behaviors.The online mindfulness based cancer recovery(MBCR)offers flexibility and guides practice across various settings,facilitating full patient engagement.This study amis to analyze the impact of a 4-week internet-delivered mindfulness-based cancer recovery program on anxiety,depression,and mindfulness among Chinese patients with breast cancer,and to evaluate the degree of satisfaction breast cancer patients experienced after participating in this program.Methods:This study utilized a two-armed,parallel,randomized controlled trial design.A total of 103 patients with breast cancer from June 2020 to January 2021 in the ward of Breast and Thyroid Surgery of a tertiary hospital in Changsha,Hunan Province were selected and randomly assigned to an intervention group(n=51)and a control group(n=52).The intervention group participated in an internet-delivered mindfulness-based cancer recovery program,which was delivered once a week for 4 weeks.Meanwhile,the control group received weekly group health education for 4 weeks.The outcomes of hospital anxiety and depression scale and mindfulness Attention Awareness Scale were evaluated at 3 distinct time points:Baseline(T1),postintervention(T2),and 1-month follow-up(T3).The satisfaction questionnaire of 4-week mindful cancer rehabilitation training program was used at T2 to evaluate patients’satisfaction with the intervention program.Generalized estimation equations were used to assess differences in anxiety,depression and mindfulness levels between groups before and after the intervention.Results:There were no statistically significant differences in demographic data and outcome index scores between the 2 groups at T1(all P>0.05),indicating that the 2 groups were comparable.The generalized estimating equation analyses showed that the intervention group had significantly better improvement in outcomes compared to the control group,particularly for anxiety(T2β=−1.30,95%CI−1.87 to−0.72;T3β=−2.78,95%CI−3.51 to−2.05)and depression(T2β=−1.92,95%CI−2.78 to−1.06;T3β=−2.96,95%CI−4.05 to−1.87;all P<0.001).Moreover,the mindfulness score in the intervention group was significantly higher than that in the control group at T2(β=3.23,95%CI 0.73 to 5.72)and T3(β=8.06,95%CI 4.37 to 11.75;both P<0.05).In addition,patients in the intervention group were satisfied with the 4-week mindfulness-based cancer recovery intervention and teaching/learning activities used to implement the program.Conclusion:In patients with breast cancer,the 4-week internet-delivered mindfulness based cancer recovery program,as a low-threshold,short-term mental health intervention,has a positive effect on reducing anxiety and depression and improving mindfulness levels.This program holds great promise as a tool for clinical nursing practice,given the high satisfaction and applicability.
文摘In a recent publication,Hu et al.(2023)have reported that individuals with high trait anxiety exhibit attentional deficits characterized by reduced inhibition of distractors and delayed attentional selection of targets,indicating impaired top-down attentional control.This commentary underscores their significant contributions to the cognitive theory of anxiety.Based on their findings,we propose a novel training approach called attentional inhibition training(AIT),aimed at improving top-down attentional control to alleviate symptoms of anxiety.Furthermore,we explore the potential application of non-invasive transcranial magnetic stimulation(TMS)for rapidly enhancing attentional control function.
基金the National Natural Science Foundation of China(82001190)Natural Sci⁃ence Foundation of Shandong Province(ZR2021LZY016)+1 种基金Natural Science Foundation of Shandong Province(ZR2020MH348)Science and Technology Foundation of Shandong Traditional Chinese Medicine(2020Q035)。
文摘OBJECTIVE To investigate whether electroacupuncture(EA)ameliorates abnormal trigeminal neuralgia(TN)orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1.METHODS A mouse infraorbital nerve transection model(pTION)of neuropathic pain was established,and EA or sham EA was used to treat ipsilateral acu⁃puncture points(GV20-Baihui and ST7-Xia⁃guan).Golgi-Cox staining and transmission elec⁃tron microscopy(TEM)were administrated to observe the changes of synaptic plasticity in the hippocampus CA1.RESULTS Stable and persistent orofacial allodynia and anxiety-like behav⁃iors induced by pT-ION were related to changes in hippocampal synaptic plasticity.Golgi stain⁃ings showed a decrease in the density of dendritic spines,especially mushroom-type dendritic spines,in hippocampal CA1 neurons of pT-ION mice.TEM results showed that the density of synapses,membrane thickness of the postsynaptic density,and length of the synaptic active zone were decreased,whereas the width of the synaptic cleft was increased in pTION mice.EA attenu⁃ated pT-ION-induced orofacial allodynia and anx⁃iety-like behaviors and effectively reversed the abnormal changes in dendritic spines and syn⁃apse of the hippocampal CA1 region.CONCLU⁃SION EA modulates synaptic plasticity of hippo⁃campal CA1 neurons,and reduces abnormal oro⁃facial pain and anxiety-like behavior,providing evidence for a TN treatment strategy.
文摘OBJECTIVE Na+/K+-ATPase(NKA)is large membrane protein expressed uni⁃versally which is indispensable for the mainte⁃nance of ionic gradient as well as neuronal excit⁃ability.The role of NKA in inflammatory regula⁃tion is still unclear.Inflammatory responses are initiated upon the activation of inflammasomes.In order to investigate the crosslink between NKA and inflammasome,NKAα1 knockout(KO)N2a cells were generated using CRISPR/Cas9 system.METHODS AND RESULTS qPCR results showed that NLRP1 and NLRP3 were upregulated in response to NKAα1 loss while both NLRC4 and AIM2 remained unaffected.Meanwhile,consistent with the change in NLRP1 and NLRP3,both the mRNA level of ASC and IL-1βwere significantly increased in NKAα1 KO cells.These data indicated that NKAα1 interfer⁃ence might influence the level of NLRP1 and NLRP3 inflammasomes in neuronal cells.Further evidence indicating the potential link between NKA and inflammasome pathway were provided using cytokine array assay where all the differen⁃tiated protein detected were closely linked to NLRP1 and NLRP3.To confirm this effect,we also observed the transcriptional levels of inflam⁃masome proteins in the brain cortex from both NKAα1+/+and NKAα1+/-mice.In line with the observation gained in NKAα1 KO cells,the mRNA level of NLRP1,NLRP3 and IL-1βwere significantly upregulated in NKAα1+/-mice brain.Interestingly,in the primary cultured astrocytes,treatment with LPS/ATP significantly reduced the mRNA and protein levels of NKAα1 expression.These data imply that a negative regulation loop between NKAα1 and inflammation may exist in the central nervous system.Since neuroinflam⁃matory mechanism is currently considered the most potential of interventions to target anxiety,we therefore perform behavioural experiments to investigate the role of NKAα1 in anxiety.Chronic restraint stress(CRS)for 10 d significantly reduced the time and frequency of entering the open arm and prolonged the retention time in the closed arm in the elevated plus-maze test.In the open field test,CRS also reduced both duration and frequency of entering into the central region.Although NKAα1 loss itself did not alter the behaviour performance in the normal condition,it exacerbated CRS-induced above behaviour abnormalities.CONCLUSION NKAα1 is regulat⁃ed upon inflammatory challenger and may be a novel target to treat anxiety.
文摘Objective:This study aimed to investigate the association of atopic dermatitis(AD)and anxiety/depression behaviors induced by AD with the intestinal microbiota.Additionally,it sought to evaluate the therapeutic potential of mannan oligosaccharide(MOS)in alleviating AD symptoms through the modulation of the gut microbiota and the enhancement of short-chain fatty acids(SCFAs)production.Methods:Female Kunming mice were challenged with 2,4-dinitrofluorobenzene(DNFB)to induce AD-like symptoms.MOS was administered orally daily for 14 days.On the 6th and 11th days post-modeling,the number of scratching bouts in mice was recorded.Following dissection,epidermal thickness,mast cell infiltration,and serum levels of inflammatory cytokines were measured.Meanwhile,cerebral levels of neurotransmitters,including 5-hydroxytryptamine(5-HT)and norepinephrine(NE),were assessed.The abundance of intestinal microbiota and fecal concentrations of SCFAs were also analyzed.Results:MOS significantly reduced AD-like symptoms by reducing inflammatory cytokines,as reflected in a significant decrease in the number of scratching bouts,epidermal thickness,mast cells and inflammatory cytokine levels.MOS intervention up-regulated the expression of 5-HT and NE,and consequently alleviated anxiety and depression-like behaviors.Furthermore,compared with the AD group,MOS intervention increased the gut microbiota abundance of mice,especially beneficial bacteria such as Bifidobacterium,Lactobacillus and Klebsiella.At the same time,these beneficial bacteria significantly increased the fecal contents of SCFAs,especially propionic acid.Correlation analysis indicated that AD amelioration was positively correlated with fecal SCFAs levels and the proliferation of certain intestinal microbes.Conclusion:MOS intervention could offer a novel approach to managing AD and its psychological comorbidities.
文摘This paper explores the anxiety that students experience in their foreign language learning.It first analyzes correlates of language anxiety,then discusses ways to identify language anxiety,and offers some suggestions for combating language anxiety.
文摘OBJECTIVE Alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in clinic.Phosphodiesterases(PDEs) are a superfamily of enzymes consisting of 11 PDE families that hydrolyze cyclicAMP(cA MP) and/or cyclicGMP(cGMP). Among them,PDE4 is critical in the control of intracellular cAMP levels and has been shown to play an important role in the regulation of ethanol consumption.However,the functional role of PDE4 in mediating alcoholism remains unclear. METHODS Ethanol drinking and preference were examined using the two-bottle choice and/or drinking-in-dark(DID) test in high alcohol preferring(HAP) animals,including C57,HAP,and PDE4-subtype knockout mice,and Fawn-Hooded(FH/Wjd) rats,treated with or without the PDE4 inhibitor rolipram or roflumilast. Ethanol withdrawal-induced anxiety-and depressive-like behaviors were examined using the elevated plusmaze,holeboard,forced-swim,and tail-suspension tests in C57 mice or FH rats in the presence of PDE4 inhibition. Levels of cAMP,CREB were determined in brain regions. RESULTS Treatment with rolipram or roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in C57 and HAP mice as well as FH rats. Mice deficient in PDE4 B,but not PDE4 D,displayed similar effects to general PDE4 inhibition. In addition,rolipram reversed ethanol withdrawal-induced anxietyand depressive-like behaviors 1 d and 14 d,respectively,following withdrawal from ethanol drinking in the two-bottle choice in C57 mice or FH rats. Locomotor activity was not changed in either mice or rats treated with the PDE4 inhibitors. Levels of cAMP,p CREB in the brain were increased by rolipram.CONCLUSION The results provide solid evidence for the important role of PDE4 in ethanol consumptionand ethanol withdrawal-induced symptoms. Inhibitors of PDE4,in particular the PDE4 B isoform,can be a novel class of treatment for alcoholism.
文摘A high level of public speaking anxiety confronts Chinese advanced learners of English,both in extemporaneous and prepared speeches.The anxiety is caused by reasons found in ESL issues,composition,and delivery.In this essay,I will illustrate different forms of speaking anxiety found in Chinese English majors.By presenting the symptoms and analyzing the causes,we shall find that it is a triumvirate of rhetoric composition,delivery,and ESL training that has produced the special anxiety for Chinese English majors.And thus it is only through the combined efforts of the triumvirate that ways of alleviating the anxiety can be found.A suggested course design that encompasses topic selection,content emphasis,progress,and assessment is finally offered.
文摘In 1995 Ince[1] wrote an article for the Times Higher Educational Supplement noting that there was little theoretical understanding of software engineering and that therefore computer studies did not constitute an academic discipline.Computing departments should be balkanised.Computing staff should be dispersed to other departments such as maths,psychology and business studies.This contro.ersy has recently been rein.igorated by McBride’s article[2] in the same paper and on the British Computer Society web site[3] arguing that in face of the massi.e decline in computing student intake onto uni.ersity undergraduate courses that the future for traditional courses is bleak.The reaction generated[3-4] reflects the anxiety within computing departments.The concern is e.ident.
基金The project supported by National Natural Science Foundation of China(81473234,U1303221)
文摘OBJECTIVE To investigated the effects of INI-0602 on nociceptive reflex,depression-associated andanxiety-related behaviors caused by neuropathic pain in sciatic nerve injury rats.METHODS Male rat were subjected to sciatic nerve injury(SNI)or sham surgery.Rat received daily treatment with INI-0602 intrathecally,at a dose of 0.25μg/10μL.The response frequency to mechanical allodynia in animals was measured with von Frey hairs on day 1,3,5,7,14,21.Rats were evaluated in the forced swimming test(FST)test,tail suspension test(TST),sucrose preference test(SPT)for depression-like behavior.We performed open field test(OFT)and elevated plus-maze test(EPM)to evaluate anxiety-associated behaviors.Besides,we investigated the alterations of NMDA receptor and the brain-derived neurotrophic factor(BDNF)and also the expression of connexin43 and connexin32,structure protein of gap junction channel,on the protein level and the number of activated astrocyte showed by immunohistochemical.RESULTS The SNI procedure produced mechanical allodynia and accompanied with depressive-like and anxiety-like behavior.Treatment with INI-0602 produced a significant analgesic effect in SNI rats at day 7(model+NS:11.017±1.506 g;model+INI-0602:31.157±1.532 g,P<0.01),and still obviously on the 21th day(31.067±1.787,P<0.01).INI-0602 could also improve the performance of sciatic nerve injury rats among program behavior tests related to depression and anxiety.In parallel with relief of pain,the alterations of NMDA receptor and the brain-derived neurotrophic factor(BDNF),involved in central sensitization and synaptic plasticity,were investigated.INI-0602 not only could inhibited spared nerve injury induced up-regulated of NR2B and phosphorylation NR2B in early and late neuropathic pain(early phase:Nr2b:2.897±0.228,P<0.01;p-Nr2b:2.984±0.236,P<0.01;late phase:Nr2b:2.594±0.187,P<0.01;p-Nr2b:3.124±0.330,P<0.01),but also could inhibit the increased of BDNF in the early(model+NS:3.637±0.381,model+INI-0602:1.148±0.372,P<0.01)and upregulate the BDNF in late stage(model+NS:0.438±0.103,model+INI-0602:1.222±0.092,P<0.01).Meanwhile,INI-0602 significantly decreased the expression of connexin43 and connexin32,structure protein of gap junction channel,on the protein level and the number of activated astrocyte showed by immunohistochemical.CONCLUSION INI-0602 blocked behavioral changes induced by neuropathic pain,suggesting that it might be a promising pharmacological approach of painemotion diseases.
基金supported by the Natural Science Foundation of Hunan Province,China(2023JJ60076)。
文摘Objective:Healthcare workers,as a high-stress professional group,face long-term high intensity workloads and complex medical environments,resulting in increasingly prominent mental health issues.In particular,the widespread presence of anxiety symptoms and somatic pain has become a major factor affecting both the quality of care and the career development of healthcare workers.This study aims to investigate the mediating and moderating roles of psychological resilience and sleep in the relationship between somatic pain and anxiety among healthcare workers.Methods:A cross-sectional questionnaire survey was conducted among 1661 healthcare workers.The instruments used included the Generalized Anxiety Disorder-7(GAD-7),item 3 from the Patient Health Questionnaire-9(PHQ-9),the 10-item Connor-Davidson Resilience Scale(CD-RISC-10)for psychological resilience,and the Visual Analogue Scale(VAS)for assessing anxiety,sleep disturbance,psychological resilience,and somatic pain.Results:The detection rate of anxiety symptoms among healthcare workers was 38.95%.Psychological resilience was significantly negatively correlated with anxiety symptoms(r=−0.451,P<0.01),sleep disturbance(r=−0.313,P<0.01),and somatic pain(r=−0.214,P<0.01).Moreover,psychological resilience partially mediated the relationship between somatic pain and anxiety(β=−0.103,P<0.01),and sleep quality moderated the latter part of the mediation model(“somatic pain-psychological resilience-anxiety”).Conclusion:Under high-intensity workloads,healthcare workers generally experience severe anxiety symptoms.Psychological resilience plays an important protective mediating role in their mental health,and sleep quality serves as a moderator in this relationship.Enhancing healthcare workers’psychological resilience and improving their sleep may promote both their physical and mental well-being.
