Aim The study focused on identification and antidepression active verification of constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan based on UPLC-PDA guided isolation technique. Methods The UPLC-P...Aim The study focused on identification and antidepression active verification of constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan based on UPLC-PDA guided isolation technique. Methods The UPLC-PDA chromatogram of Xiaoyaosan was compared with that of Angelica Sinensis Radix. The relative retention time of each peak and the Uhraviolet spectra providing by PDA were used in the analyses. Constituents were isola- ted from Angelica Sinensis Radix under the guidance of UPLC-PDA investigation. Structures of the isolates were elu- cidated by NMR techniques. Anti-depression effect was evaluated on glutamate-induced neurons. Results Five marker peaks of Xiaoyaosan fingerprint were belong to Angelica Sinensis Radix, and they were determined as conife- ryl ferulate（ I）, E-butylidenephthalide （ II）, ligustilide （III）, Z-butylidenephthalide （ IV ）, 14-Acetoxy-12-sene- cioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-l-ol（V）. Compound V was isolated from the plants of Umbelliferae for the first time. Treatment with compound I, III, IV can protect PC12 and SH-SY5Y cell from glutamate-induced cytotoxicity. Antidepression bioactivity of compound I was first investigated. Conclusion UPLC-PDA guided iso-lation technique was confirmed to be a rapid and accurate method to identify the main active constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan.展开更多
Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability a...Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects,seriously limiting its application in pharmaceutics.Herein,we demonstrated the fabrication of ARI and poly(methyl vinyl etherco-maleic anhydride)(PVMMA)composite nanoparticles(PA NPs)using the supercritical antisolvent(SAS)process for enhancing its water-solubility and curative anti-depressant effects.Initially,the optimal experimental conditions(ARI/PVMMA mass ratio of 1:6,pressure of 10MPa,and solution flow rate of 0.75ml min^(-1))were determined by a 23 factorial experimental design,resulting in the PA NPs with an excellent particle morphology.In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide(LPS).Similarly,mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior.Importantly,compared with free ARI,the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs.Together,the innovative PA NPs designed by SAS processmight provide a candidate for developing new ARI-based nano-formulations.展开更多
Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
Antidepressants are the main drugs used to treat depression,but they have not been shown to be effective in the treatment of child and adolescent depression.However,many adolescent depression treatment guidelines stil...Antidepressants are the main drugs used to treat depression,but they have not been shown to be effective in the treatment of child and adolescent depression.However,many adolescent depression treatment guidelines still recommend the use of antidepressants,especially specific serotonin re-uptake inhibitors.Previous studies have suggested that antidepressants have little therapeutic effect but many side effects,such as switching to mania,suicide,and non-suicidal self injury(NSSI),in the treatment of child and adolescent depression.In the process of developing guidelines,drug recommendations should not only focus on impro-ving symptoms,but they should also consider potential side effects.This review discusses the serious side effects of antidepressants,including switching to mania,suicide,and NSSI.展开更多
BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotoni...BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotonin reuptake inhibitors(SSRIs)are frequently used in the treatment of depression;however,their efficacy in addressing major depressive disorder(MDD)in adults following TBI remains uncertain.AIM To investigate the efficacy of SSRIs in the treatment of MDD after TBI.METHODS A comprehensive search across multiple databases was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,encompassing studies published until May 2024.This review focused on studies that examined the efficacy of SSRIs in the treatment of MDD following TBI.Studies were assessed based sample size,treatment duration,treatment methodologies,severity of brain injury,assessment techniques,and drug response.A random-effects model was used to derive the summary effect size.RESULTS Eight studies compared the reduction in depression scores in patients with MDD after TBI and SSRI treatment.The eight studies did not exhibit heterogeneity(I^(2)=38%).The depression score for MDD after TBI in the SSRI group decreased more than that in the control group[odds ratio(OR)1.68,95%CI:1.09-2.58,P=0.02].The adverse reactions after treatment included diarrhea,dizziness,dry mouth,nausea,or vomiting.There was no difference in the incidence of adverse reactions after treatment between the two groups(OR 1.16,95%CI:0.78-1.73,P=0.46).These studies did not show significant heterogeneity(I^(2)=44%).CONCLUSION SSRIs may be effective in treating patients with MDD after TBI.Adequately powered,randomized,controlled trials are required to confirm these findings.展开更多
Agitation is a neuropsychiatric syndrome characterized by excessive motor and/or verbal behaviors,with or without aggressive behaviors.The prevalence of agitation in Alzheimer’s disease varies from 5%to over 50%.Mult...Agitation is a neuropsychiatric syndrome characterized by excessive motor and/or verbal behaviors,with or without aggressive behaviors.The prevalence of agitation in Alzheimer’s disease varies from 5%to over 50%.Multiple factors have been implicated in its pathophysiology,including disease stage,comorbidity with other symptoms(e.g.,psychosis,anxiety/depression),and psychosocial factors.Ruling out delirium and identifying environmental triggers are fundamental steps in the management of agitation in Alzheimer’s disease.For establishing an effective therapeutic plan,it is important to define duration,severity,and potential for harm.While non-pharmacological approaches are considered the first line of intervention,pharmacological agents are frequently used in the treatment of agitation.Antipsychotics are commonly used in acute agitation.For chronic agitation,serotonin-selective reuptake inhibitors,especially citalopram and escitalopram,are often preferred due to safety concerns associated with the longterm use of antipsychotics.Promising novel strategies,such as new compounds and neuromodulation,are likely to be incorporated into agitation therapeutics in the next few years.展开更多
BACKGROUND Non-suicidal self-injury(NSSI)in adolescents is a strong predictor of suicide and a significant mental health problem worldwide.Previous studies have identified various risk factors for NSSI.However,studies...BACKGROUND Non-suicidal self-injury(NSSI)in adolescents is a strong predictor of suicide and a significant mental health problem worldwide.Previous studies have identified various risk factors for NSSI.However,studies have not explored the association between inflammatory factors and NSSI in adolescents.AIM To investigate inflammatory marker changes post-antidepressant treatment and their association with suicide risk in NSSI adolescents.METHODS The study enrolled 68 adolescents with NSSI behaviors.The participants were divided into high and low suicide risk groups(n=38 and n=30,respectively)based on their scores on the Suicide Risk Factors Assessment Scale.Symptom severity was assessed at baseline and after six weeks of treatment.Blood samples were obtained to monitor for inflammatory factors.RESULTS The high suicide risk group exhibited higher levels of interferon(IFN)-αand interleukin(IL)-10 than the low suicide risk group.Scores on the Hamilton Anxiety Rating Scale,Hamilton Depression Rating Scale,and Insomnia Severity Index decreased significantly post-treatment.Tumor necrosis factor-α,IL-10,IL-6,IL-1,and IL-12 levels decreased,whereas IFN-γ,IL-4,and IFN-αlevels increased.IL-10 levels were correlated with the severity of suicide risk factors.CONCLUSION Adolescents with NSSI exhibit distinct inflammatory markers based on suicide risk,which change following treatment.Moreover,IL-10 levels are associated with suicide risk.These biomarkers may help assess suicide risk in clinical settings.展开更多
[Objectives]This study was conducted to perform visual analysis of the research hotspots and development trends of Cyperi Rhizoma in the field of antidepressant based on CiteSpace,so as to explore the application and ...[Objectives]This study was conducted to perform visual analysis of the research hotspots and development trends of Cyperi Rhizoma in the field of antidepressant based on CiteSpace,so as to explore the application and development direction of Cyperi Rhizoma in the field of antidepressant.[Methods]Highly-relevant literatures were selected from the core database of China National Knowledge Infrastructure(CNKI),and CiteSpace and WPS office software were employed to visually analyze relevant contents such as publishing institutions,scholars,keywords,publishing time,and citation frequency.[Results]A total of 297 domestic relevant literatures were selected.Most of the publications,institutions and authors were concentrated in universities,affiliated institutions and scientific research institutes of traditional Chinese medicine in China,and no relatively novel applied research direction has emerged.At present,the hot spots and frontiers of application were mostly concentrated in its role in treating depression,anxiety,gynecological diseases and other disorders.[Conclusions]The research on Cyperi Rhizoma for its antidepressant effects in China originated in the late 20 th century.From 2004 to 2024,studies have primarily focused on its pharmacological principles,mechanisms of action,and classification,while the exploration of its application in specific depressive disorders was limited.Overall,research progress has been relatively slow.Currently,further efforts are needed to optimize the active antidepressant components of Cyperi Rhizoma and clarify its mechanisms of action,which will facilitate its broader application in treating various stages of depressive disorders.展开更多
The high comorbidity rates of depression and chronic obstructive pulmonary disease(COPD)have garnered widespread attention.As a refractory disease,its long-term stress effects exacerbate the coexistence of depression....The high comorbidity rates of depression and chronic obstructive pulmonary disease(COPD)have garnered widespread attention.As a refractory disease,its long-term stress effects exacerbate the coexistence of depression.Depression is linked to a decline in lung function in patients with COPD through reduced heart rate variability,increased inflammatory cytokines,dysregulation of the hypothalamic-pituitary-adrenal axis,and the interplay of various biological and psychological factors.Sole reliance on biomedical treatment cannot fully counteract these negative effects,which are detrimental to improving patients’quality of life and long-term prognosis.Antidepressant medications and traditional Chinese medicine combined with conventional COPD therapy,psychotherapy(e.g.,cognitive behavioral therapy,mindfulness training),and lifestyle adjustments(e.g.,yoga,qigong,or walking)can not only alleviate depression and compensate for the limitations of biomedical approaches but also help improve heart rate variability and lung function.In this editorial,we suggest that clinicians,when prescribing antidepressants,must carefully weigh the benefit-risk ratio based on the patient’s specific physical condition to ensure precise medication use.展开更多
To the editor:A wide range of affective disorders affects people of all ages globally and contributes significantly to the global disease burden.1 In China,a nationwide survey found a 3.21% prevalence of affective dis...To the editor:A wide range of affective disorders affects people of all ages globally and contributes significantly to the global disease burden.1 In China,a nationwide survey found a 3.21% prevalence of affective disorders in children and adolescents,with major depressive disorder(MDD)at 2.00%and bipolar disorder at 0.86%.展开更多
A recent meta-analysis has suggested a 5-HTR1A promoter variant may predict antidepressant response.The present review comments on the claims made in view of sensitivity issues and issues pertaining to genetic exposur...A recent meta-analysis has suggested a 5-HTR1A promoter variant may predict antidepressant response.The present review comments on the claims made in view of sensitivity issues and issues pertaining to genetic exposure.We also alert to errors in the original data that had been carried over.Specifically,primers meant to amplify the HTR1A gene aligned to the BDNF gene sequence.Alleles had been confounded owing to DNA strand ambiguities and demographic information proved inaccurate.In the light of these findings,adherence to PRISMA guidelines and use of the Newcastle-Ottawa Scale did not safeguard against bias.More after action reviews are encouraged to identify factors likely to interfere with estimates of genetic risk in large data sets.These may result from pooling of ethnic groups,the use of binary data or other formats that are not human-readable,the introduction of surrogate identifiers and a failure to reverseengineer previously published experimental protocols.Unless the above challenges are met,sequence variants are unlikely to inform personalized medicine strategies in psychiatry.展开更多
Background:The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression,but the underlying cellular and molecular mechanisms remain unclear.Implicated in de...Background:The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression,but the underlying cellular and molecular mechanisms remain unclear.Implicated in depression regulation,the neuropeptide pituitary adenylate cyclase-activating polypeptide(PACAP)is investigated here to examine its role in mediating the rapid antidepressant response.Methods:The onset of antidepressant response was assessed through depression-related behavioral paradigms.The signaling mechanism of PACAP in the hippocampal dentate gyrus(DG)was evaluated by utilizing site-directed gene knockdown,pharmacological interventions,or optogenetic manipulations.Overall,446 mice were used for behavioral and molecular signaling testing.Mice were divided into control or experimental groups randomly in each experiment,and the experimental manipulations included:chronic paroxetine treatments(4 d,9 d,14 d)or a single treatment of ketamine;social defeat or lipopolysaccharides-injection induced depression models;different doses of PACAP(0.4 ng/site,2 ng/site,4 ng/site;microinjected into the hippocampal DG);pharmacological intra-DG interventions(CALM and PACAP6-38);intra-DG viral-mediated PACAP RNAi;and opotogenetics using channelrhodopsins 2(ChR2)or endoplasmic natronomonas halorhodopsine 3.0(eNpHR3.0).Behavioral paradigms included novelty suppressed feeding test,tail suspension test,forced swimming test,and sucrose preference test.Western blotting,ELISA,or quantitative real-time PCR(RT-PCR)analysis were used to detect the expressions of proteins/peptides or genes in the hippocampus.Results:Chronic administration of the slow-onset antidepressant paroxetine resulted in an increase in hippocampal PACAP expression,and intra-DG blockade of PACAP attenuated the onset of the antidepressant response.The levels of hippocampal PACAP expression were reduced in both two distinct depression animal models and intra-DG knockdown of PACAP induced depression-like behaviors.Conversely,a single infusion of PACAP into the DG region produced a rapid and sustained antidepressant response in both normal and chronically stressed mice.Optogenetic intra-DG excitation of PACAP-expressing neurons instantly elicited antidepressant responses,while optogenetic inhibition induced depression-like behaviors.The longer optogenetic excitation/inhibition elicited the more sustained antidepressant/depression-like responses.Intra-DG PACAP infusion immediately facilitated the signaling for rapid antidepressant response by inhibiting calcium/calmodulin-dependent protein kinaseⅡ(CaM KⅡ)-eukaryotic elongation factor 2(eEF2)and activating the mammalian target of rapamycin(mTOR).Pre-activation of CaMKⅡsignaling within the DG blunted PACAP-induced rapid antidepressant response as well as eEF2-mTOR-brain-derived neurotrophic factor(BDNF)signaling.Finally,acute ketamine treatment upregulated hippocampal PACAP expression,whereas intraDG blockade of PACAP signaling attenuated ketamine’s rapid antidepressant response.Conclusions:Activation of hippocampal PACAP signaling induces a rapid antidepressant response through the regulation of CaMKⅡinhibition-governed eEF2-mTOR-BDNF signaling.展开更多
The antidepressive effect of Xiaoyaosan is doubtless by researches while the potential antidepressive ac- tive ingredients and their mechanisms remain unclear. In order to explain the antidepressive effect of Xiaoyaos...The antidepressive effect of Xiaoyaosan is doubtless by researches while the potential antidepressive ac- tive ingredients and their mechanisms remain unclear. In order to explain the antidepressive effect of Xiaoyaosan, all of the recent reports were sought out on the current situation of the antidepressive monomer compositions of Xi- aoyaosan and their mechanism. By exploring the relationship between the effects and the active ingredients, the mechanism and the active ingredients, the antidepressive active ingredients such as quercetin, isorhamnetin, isoliquiritigenin, saikosaponinA, saikosaponinD, glycyrrhiz- kaempferol, liquiritin, isoliquiritin, liquiritigenin, inate, paeoniflorin, albiflorin, ferulic acid, curcumin and their mechanism of antidepressive such as regulating the monoamine neurotransmitter systems, regulating the neuroendocrine system, affecting the neural plasticity and neu- affecting the cytokines level, anti-oxidative stress were rotrophic, affecting the cellular and molecular mechanisms , summarized. By the overview in the level of monomer rather than formulae, we uncovered the antidepressive mech- anism of Xiaoyaosan and further confirmed that Xiaoyaosan, as a classic antidepressive Chinese prescription, had many characteristics, such as multi-level , multi-channel, multi-target and so on .展开更多
Aim To study the influence of SiniSan on the Tryptophan- kynurenine（TRP-KYN）pathway, the activity and content of the key metabolism enzyme indoleamine2, 3-dioxygenase （IDO）. Methods The mice model was established ...Aim To study the influence of SiniSan on the Tryptophan- kynurenine（TRP-KYN）pathway, the activity and content of the key metabolism enzyme indoleamine2, 3-dioxygenase （IDO）. Methods The mice model was established by intraperitoneal injection LPS （ 1 mg · kg^-1 ）. Using ELISA to detect the contents of IFN-γin serum. The content of Tryptophan and kynurenine in brain tissue were detected by using HPLC-MS/MS technique. The mRNA expression level of IDO in brain tissue was detected by using real-time PCR. Results 4 hours after the LPS injection, the immobility time of model group mice prolonged. The content of IFN-~/in serum increased significantly （P 〈 0.05）. Meanwhile, the activity of IDO in brain tissue and the mRNA expression level of IDO increased. SiniSan could short the immobility time of mice, reduced the content of IFN-γin serum （P 〈 0.05）. It could also inhibit the activity of IDO and the expression of mRNA（P 〈 0.01 ）. Conclusion SiniSan blocks the pathway of IDO activation, inhibit the activity of IDO and reduce the content of it. SiniSan produces antidepressant effect by adjusting the TRP-KYN metabolism.展开更多
Synephrine hydrochloride,an alkaloid compound extracted from immature bitter orange,has many pharmacological effects such as anticancer effect,antioxidant effect and antidepression effect.In this paper,the pharmacolog...Synephrine hydrochloride,an alkaloid compound extracted from immature bitter orange,has many pharmacological effects such as anticancer effect,antioxidant effect and antidepression effect.In this paper,the pharmacological effects and mechanism of synephrine hydrochloride were reviewed in order to provide a theoretical basis for the development and application of synephrine hydrochloride.展开更多
Diabetic neuropathy is a common complication of both type 1 and type 2 diabetes,which affects over 90% of the diabetic patients.Although pain is one of the main symptoms of diabetic neuropathy,its pathophysiological m...Diabetic neuropathy is a common complication of both type 1 and type 2 diabetes,which affects over 90% of the diabetic patients.Although pain is one of the main symptoms of diabetic neuropathy,its pathophysiological mechanisms are not yet fully known.It is widely accepted that the toxic effects of hyperglycemia play an important role in the development of this complication,but several other hypotheses have been postulated.The management of diabetic neuropathic pain consists basically in excluding other causes of painful peripheral neuropathy,improving glycemic control as a prophylactic therapy and using medications to alleviate pain.First line drugs for pain relief include anticonvulsants,such as pregabalin and gabapentin and antidepressants,especial y those that act to inhibit the reuptake of serotonin and noradrenaline.In addition,there is experimental and clinical evidence that opioids can be helpful in pain control,mainly if associated with first line drugs.Other agents,including for topical application,such as capsaicin cream and lidocaine patches,have also been proposed to be useful as adjuvants in the control of diabetic neuropathic pain,but the clinical evidence is insufficient to support their use.In conclusion,a better understanding of the mechanisms underlying diabetic neuropathic pain will contribute to the search of new therapies,but also to the improvement of the guidelines to optimize pain control with the drugs currently available.展开更多
Perilla frutescens(Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have ...Perilla frutescens(Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens(EOPF) attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress(CUMS)-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF(3, 6, and 9 mg·kg-1) and a positive control drug fluoxetine(20 mg·kg-1) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3rd week. Open-field test, sucrose consumption test, tail suspension test(TST), and forced swimming test(FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine(5-HT) and its metabolite, 5-hydroxyindoleacetic acid(5-HIAA), in mouse hippocampus were determined by HPLC–ECD. Serum interleukin(IL)-1, IL-6, and tumor necrosis factor(TNF)-α levels were evaluated by enzyme-linked immunosorbent assay(ELISA). The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between alteration of serotonergic responses and anti-inflammatory effects.展开更多
Depression is the most disabling disorder world- wide that accounts for the highest proportion of global burden attributable to mental disorders. Major depressive disorder （MDD） is characterized by deep sadness, red...Depression is the most disabling disorder world- wide that accounts for the highest proportion of global burden attributable to mental disorders. Major depressive disorder （MDD） is characterized by deep sadness, reduced energy, vegetative nervous system dysregulation, cognitive dysfunction, and even a high suicidal tendency. Although other treatment choices are available, antidepressant medication is the front-line treatment option for MDD. Regarding clinical efficacy, only - 50% of patients respond to frontline antide pressants, and 〈33% obtain remission. Currently, objective indexes to guide clinical decisions are still lacking. Further- more, knowledge about the neurobiological mechanisms underlying discrepant antidepressant outcomes is still also fragmentary. In the present review, we discuss the current research progress and clinical opinions on MDD in China.展开更多
Research to date indicates that the number of coronary artery bypass graft （CABG） surgery patients affected by depression （i.e., major, minor, dysthymia） approximates between 30% and 40% of all cases. A longstandi...Research to date indicates that the number of coronary artery bypass graft （CABG） surgery patients affected by depression （i.e., major, minor, dysthymia） approximates between 30% and 40% of all cases. A longstanding empirical interest on psychosocial factors in CABG surgery patients highlights an association with increased risk of morbidity in the short and longer term. Recent evidence suggests that both depression and anxiety increase the risk for mortality and morbidity after CABG surgery independent of medical factors, although the behavioral and biological mechanisms are poorly understood. Though neither depression nor anxiety seem to markedly affect neuropsy- chological dysfunction, depression confers a risk for incident delirium. Following a comprehensive overview of recent literature, practical advice is described for clinicians taking into consideration possible screening aids to improve recognition of anxiety and depression among CABG surgery patients. An overview of contemporary interventions and randomized, controlled trials are described, along with suggestions for future CABG surgery research.展开更多
文摘Aim The study focused on identification and antidepression active verification of constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan based on UPLC-PDA guided isolation technique. Methods The UPLC-PDA chromatogram of Xiaoyaosan was compared with that of Angelica Sinensis Radix. The relative retention time of each peak and the Uhraviolet spectra providing by PDA were used in the analyses. Constituents were isola- ted from Angelica Sinensis Radix under the guidance of UPLC-PDA investigation. Structures of the isolates were elu- cidated by NMR techniques. Anti-depression effect was evaluated on glutamate-induced neurons. Results Five marker peaks of Xiaoyaosan fingerprint were belong to Angelica Sinensis Radix, and they were determined as conife- ryl ferulate（ I）, E-butylidenephthalide （ II）, ligustilide （III）, Z-butylidenephthalide （ IV ）, 14-Acetoxy-12-sene- cioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-l-ol（V）. Compound V was isolated from the plants of Umbelliferae for the first time. Treatment with compound I, III, IV can protect PC12 and SH-SY5Y cell from glutamate-induced cytotoxicity. Antidepression bioactivity of compound I was first investigated. Conclusion UPLC-PDA guided iso-lation technique was confirmed to be a rapid and accurate method to identify the main active constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan.
基金supported by the National Natural Science Foundation of China(NSFC,81971734,32071323,32271410),the Program for Innovative Research Team in Science and Technology in Fujian Province.
文摘Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects,seriously limiting its application in pharmaceutics.Herein,we demonstrated the fabrication of ARI and poly(methyl vinyl etherco-maleic anhydride)(PVMMA)composite nanoparticles(PA NPs)using the supercritical antisolvent(SAS)process for enhancing its water-solubility and curative anti-depressant effects.Initially,the optimal experimental conditions(ARI/PVMMA mass ratio of 1:6,pressure of 10MPa,and solution flow rate of 0.75ml min^(-1))were determined by a 23 factorial experimental design,resulting in the PA NPs with an excellent particle morphology.In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide(LPS).Similarly,mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior.Importantly,compared with free ARI,the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs.Together,the innovative PA NPs designed by SAS processmight provide a candidate for developing new ARI-based nano-formulations.
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
文摘Antidepressants are the main drugs used to treat depression,but they have not been shown to be effective in the treatment of child and adolescent depression.However,many adolescent depression treatment guidelines still recommend the use of antidepressants,especially specific serotonin re-uptake inhibitors.Previous studies have suggested that antidepressants have little therapeutic effect but many side effects,such as switching to mania,suicide,and non-suicidal self injury(NSSI),in the treatment of child and adolescent depression.In the process of developing guidelines,drug recommendations should not only focus on impro-ving symptoms,but they should also consider potential side effects.This review discusses the serious side effects of antidepressants,including switching to mania,suicide,and NSSI.
文摘BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotonin reuptake inhibitors(SSRIs)are frequently used in the treatment of depression;however,their efficacy in addressing major depressive disorder(MDD)in adults following TBI remains uncertain.AIM To investigate the efficacy of SSRIs in the treatment of MDD after TBI.METHODS A comprehensive search across multiple databases was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,encompassing studies published until May 2024.This review focused on studies that examined the efficacy of SSRIs in the treatment of MDD following TBI.Studies were assessed based sample size,treatment duration,treatment methodologies,severity of brain injury,assessment techniques,and drug response.A random-effects model was used to derive the summary effect size.RESULTS Eight studies compared the reduction in depression scores in patients with MDD after TBI and SSRI treatment.The eight studies did not exhibit heterogeneity(I^(2)=38%).The depression score for MDD after TBI in the SSRI group decreased more than that in the control group[odds ratio(OR)1.68,95%CI:1.09-2.58,P=0.02].The adverse reactions after treatment included diarrhea,dizziness,dry mouth,nausea,or vomiting.There was no difference in the incidence of adverse reactions after treatment between the two groups(OR 1.16,95%CI:0.78-1.73,P=0.46).These studies did not show significant heterogeneity(I^(2)=44%).CONCLUSION SSRIs may be effective in treating patients with MDD after TBI.Adequately powered,randomized,controlled trials are required to confirm these findings.
基金Supported by the National Institutes of Health/National Institute on Aging,No.1R21AG091282.
文摘Agitation is a neuropsychiatric syndrome characterized by excessive motor and/or verbal behaviors,with or without aggressive behaviors.The prevalence of agitation in Alzheimer’s disease varies from 5%to over 50%.Multiple factors have been implicated in its pathophysiology,including disease stage,comorbidity with other symptoms(e.g.,psychosis,anxiety/depression),and psychosocial factors.Ruling out delirium and identifying environmental triggers are fundamental steps in the management of agitation in Alzheimer’s disease.For establishing an effective therapeutic plan,it is important to define duration,severity,and potential for harm.While non-pharmacological approaches are considered the first line of intervention,pharmacological agents are frequently used in the treatment of agitation.Antipsychotics are commonly used in acute agitation.For chronic agitation,serotonin-selective reuptake inhibitors,especially citalopram and escitalopram,are often preferred due to safety concerns associated with the longterm use of antipsychotics.Promising novel strategies,such as new compounds and neuromodulation,are likely to be incorporated into agitation therapeutics in the next few years.
基金Supported by the Natural Science Basic Research Program of Shaanxi Province,No.2022SF526 and No.2022SF509the National Natural Science Foundation of China,No.82301737.
文摘BACKGROUND Non-suicidal self-injury(NSSI)in adolescents is a strong predictor of suicide and a significant mental health problem worldwide.Previous studies have identified various risk factors for NSSI.However,studies have not explored the association between inflammatory factors and NSSI in adolescents.AIM To investigate inflammatory marker changes post-antidepressant treatment and their association with suicide risk in NSSI adolescents.METHODS The study enrolled 68 adolescents with NSSI behaviors.The participants were divided into high and low suicide risk groups(n=38 and n=30,respectively)based on their scores on the Suicide Risk Factors Assessment Scale.Symptom severity was assessed at baseline and after six weeks of treatment.Blood samples were obtained to monitor for inflammatory factors.RESULTS The high suicide risk group exhibited higher levels of interferon(IFN)-αand interleukin(IL)-10 than the low suicide risk group.Scores on the Hamilton Anxiety Rating Scale,Hamilton Depression Rating Scale,and Insomnia Severity Index decreased significantly post-treatment.Tumor necrosis factor-α,IL-10,IL-6,IL-1,and IL-12 levels decreased,whereas IFN-γ,IL-4,and IFN-αlevels increased.IL-10 levels were correlated with the severity of suicide risk factors.CONCLUSION Adolescents with NSSI exhibit distinct inflammatory markers based on suicide risk,which change following treatment.Moreover,IL-10 levels are associated with suicide risk.These biomarkers may help assess suicide risk in clinical settings.
基金Supported by Undergraduate Innovation and Enterpreneurship Training Program of Guangxi(S202310600067)Guangxi First-class Discipline Construction Project(GJKY[2022]1).
文摘[Objectives]This study was conducted to perform visual analysis of the research hotspots and development trends of Cyperi Rhizoma in the field of antidepressant based on CiteSpace,so as to explore the application and development direction of Cyperi Rhizoma in the field of antidepressant.[Methods]Highly-relevant literatures were selected from the core database of China National Knowledge Infrastructure(CNKI),and CiteSpace and WPS office software were employed to visually analyze relevant contents such as publishing institutions,scholars,keywords,publishing time,and citation frequency.[Results]A total of 297 domestic relevant literatures were selected.Most of the publications,institutions and authors were concentrated in universities,affiliated institutions and scientific research institutes of traditional Chinese medicine in China,and no relatively novel applied research direction has emerged.At present,the hot spots and frontiers of application were mostly concentrated in its role in treating depression,anxiety,gynecological diseases and other disorders.[Conclusions]The research on Cyperi Rhizoma for its antidepressant effects in China originated in the late 20 th century.From 2004 to 2024,studies have primarily focused on its pharmacological principles,mechanisms of action,and classification,while the exploration of its application in specific depressive disorders was limited.Overall,research progress has been relatively slow.Currently,further efforts are needed to optimize the active antidepressant components of Cyperi Rhizoma and clarify its mechanisms of action,which will facilitate its broader application in treating various stages of depressive disorders.
文摘The high comorbidity rates of depression and chronic obstructive pulmonary disease(COPD)have garnered widespread attention.As a refractory disease,its long-term stress effects exacerbate the coexistence of depression.Depression is linked to a decline in lung function in patients with COPD through reduced heart rate variability,increased inflammatory cytokines,dysregulation of the hypothalamic-pituitary-adrenal axis,and the interplay of various biological and psychological factors.Sole reliance on biomedical treatment cannot fully counteract these negative effects,which are detrimental to improving patients’quality of life and long-term prognosis.Antidepressant medications and traditional Chinese medicine combined with conventional COPD therapy,psychotherapy(e.g.,cognitive behavioral therapy,mindfulness training),and lifestyle adjustments(e.g.,yoga,qigong,or walking)can not only alleviate depression and compensate for the limitations of biomedical approaches but also help improve heart rate variability and lung function.In this editorial,we suggest that clinicians,when prescribing antidepressants,must carefully weigh the benefit-risk ratio based on the patient’s specific physical condition to ensure precise medication use.
基金the Tianjin Health Research Project(Grant No.TJWJ2023MS038)Tianjin Education Commission Research Project(Grant No.2023KJ044)S&T Program of Hebei(SG2021189)。
文摘To the editor:A wide range of affective disorders affects people of all ages globally and contributes significantly to the global disease burden.1 In China,a nationwide survey found a 3.21% prevalence of affective disorders in children and adolescents,with major depressive disorder(MDD)at 2.00%and bipolar disorder at 0.86%.
文摘A recent meta-analysis has suggested a 5-HTR1A promoter variant may predict antidepressant response.The present review comments on the claims made in view of sensitivity issues and issues pertaining to genetic exposure.We also alert to errors in the original data that had been carried over.Specifically,primers meant to amplify the HTR1A gene aligned to the BDNF gene sequence.Alleles had been confounded owing to DNA strand ambiguities and demographic information proved inaccurate.In the light of these findings,adherence to PRISMA guidelines and use of the Newcastle-Ottawa Scale did not safeguard against bias.More after action reviews are encouraged to identify factors likely to interfere with estimates of genetic risk in large data sets.These may result from pooling of ethnic groups,the use of binary data or other formats that are not human-readable,the introduction of surrogate identifiers and a failure to reverseengineer previously published experimental protocols.Unless the above challenges are met,sequence variants are unlikely to inform personalized medicine strategies in psychiatry.
基金supported by the National Key Research and Development Program of China(2022YFE0201000)the National Natural Science Foundation of China(82174002,82104416,82204652)the High-Level University Development Program of Guangdong Province,and the Guangzhou Key Science and Technology Research and Development Project(202206010109)。
文摘Background:The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression,but the underlying cellular and molecular mechanisms remain unclear.Implicated in depression regulation,the neuropeptide pituitary adenylate cyclase-activating polypeptide(PACAP)is investigated here to examine its role in mediating the rapid antidepressant response.Methods:The onset of antidepressant response was assessed through depression-related behavioral paradigms.The signaling mechanism of PACAP in the hippocampal dentate gyrus(DG)was evaluated by utilizing site-directed gene knockdown,pharmacological interventions,or optogenetic manipulations.Overall,446 mice were used for behavioral and molecular signaling testing.Mice were divided into control or experimental groups randomly in each experiment,and the experimental manipulations included:chronic paroxetine treatments(4 d,9 d,14 d)or a single treatment of ketamine;social defeat or lipopolysaccharides-injection induced depression models;different doses of PACAP(0.4 ng/site,2 ng/site,4 ng/site;microinjected into the hippocampal DG);pharmacological intra-DG interventions(CALM and PACAP6-38);intra-DG viral-mediated PACAP RNAi;and opotogenetics using channelrhodopsins 2(ChR2)or endoplasmic natronomonas halorhodopsine 3.0(eNpHR3.0).Behavioral paradigms included novelty suppressed feeding test,tail suspension test,forced swimming test,and sucrose preference test.Western blotting,ELISA,or quantitative real-time PCR(RT-PCR)analysis were used to detect the expressions of proteins/peptides or genes in the hippocampus.Results:Chronic administration of the slow-onset antidepressant paroxetine resulted in an increase in hippocampal PACAP expression,and intra-DG blockade of PACAP attenuated the onset of the antidepressant response.The levels of hippocampal PACAP expression were reduced in both two distinct depression animal models and intra-DG knockdown of PACAP induced depression-like behaviors.Conversely,a single infusion of PACAP into the DG region produced a rapid and sustained antidepressant response in both normal and chronically stressed mice.Optogenetic intra-DG excitation of PACAP-expressing neurons instantly elicited antidepressant responses,while optogenetic inhibition induced depression-like behaviors.The longer optogenetic excitation/inhibition elicited the more sustained antidepressant/depression-like responses.Intra-DG PACAP infusion immediately facilitated the signaling for rapid antidepressant response by inhibiting calcium/calmodulin-dependent protein kinaseⅡ(CaM KⅡ)-eukaryotic elongation factor 2(eEF2)and activating the mammalian target of rapamycin(mTOR).Pre-activation of CaMKⅡsignaling within the DG blunted PACAP-induced rapid antidepressant response as well as eEF2-mTOR-brain-derived neurotrophic factor(BDNF)signaling.Finally,acute ketamine treatment upregulated hippocampal PACAP expression,whereas intraDG blockade of PACAP signaling attenuated ketamine’s rapid antidepressant response.Conclusions:Activation of hippocampal PACAP signaling induces a rapid antidepressant response through the regulation of CaMKⅡinhibition-governed eEF2-mTOR-BDNF signaling.
文摘The antidepressive effect of Xiaoyaosan is doubtless by researches while the potential antidepressive ac- tive ingredients and their mechanisms remain unclear. In order to explain the antidepressive effect of Xiaoyaosan, all of the recent reports were sought out on the current situation of the antidepressive monomer compositions of Xi- aoyaosan and their mechanism. By exploring the relationship between the effects and the active ingredients, the mechanism and the active ingredients, the antidepressive active ingredients such as quercetin, isorhamnetin, isoliquiritigenin, saikosaponinA, saikosaponinD, glycyrrhiz- kaempferol, liquiritin, isoliquiritin, liquiritigenin, inate, paeoniflorin, albiflorin, ferulic acid, curcumin and their mechanism of antidepressive such as regulating the monoamine neurotransmitter systems, regulating the neuroendocrine system, affecting the neural plasticity and neu- affecting the cytokines level, anti-oxidative stress were rotrophic, affecting the cellular and molecular mechanisms , summarized. By the overview in the level of monomer rather than formulae, we uncovered the antidepressive mech- anism of Xiaoyaosan and further confirmed that Xiaoyaosan, as a classic antidepressive Chinese prescription, had many characteristics, such as multi-level , multi-channel, multi-target and so on .
文摘Aim To study the influence of SiniSan on the Tryptophan- kynurenine（TRP-KYN）pathway, the activity and content of the key metabolism enzyme indoleamine2, 3-dioxygenase （IDO）. Methods The mice model was established by intraperitoneal injection LPS （ 1 mg · kg^-1 ）. Using ELISA to detect the contents of IFN-γin serum. The content of Tryptophan and kynurenine in brain tissue were detected by using HPLC-MS/MS technique. The mRNA expression level of IDO in brain tissue was detected by using real-time PCR. Results 4 hours after the LPS injection, the immobility time of model group mice prolonged. The content of IFN-~/in serum increased significantly （P 〈 0.05）. Meanwhile, the activity of IDO in brain tissue and the mRNA expression level of IDO increased. SiniSan could short the immobility time of mice, reduced the content of IFN-γin serum （P 〈 0.05）. It could also inhibit the activity of IDO and the expression of mRNA（P 〈 0.01 ）. Conclusion SiniSan blocks the pathway of IDO activation, inhibit the activity of IDO and reduce the content of it. SiniSan produces antidepressant effect by adjusting the TRP-KYN metabolism.
基金Supported by the Talent Training Program for the Reform and Development of Local Colleges and Universities of the Central Government(2020GSP16)Heilongjiang Province Key Research and Development Plan Guidance Project(GZ20220039)Innovation and Entrepreneurship Training Program for College Students in Heilongjiang Province(202210223010).
文摘Synephrine hydrochloride,an alkaloid compound extracted from immature bitter orange,has many pharmacological effects such as anticancer effect,antioxidant effect and antidepression effect.In this paper,the pharmacological effects and mechanism of synephrine hydrochloride were reviewed in order to provide a theoretical basis for the development and application of synephrine hydrochloride.
文摘Diabetic neuropathy is a common complication of both type 1 and type 2 diabetes,which affects over 90% of the diabetic patients.Although pain is one of the main symptoms of diabetic neuropathy,its pathophysiological mechanisms are not yet fully known.It is widely accepted that the toxic effects of hyperglycemia play an important role in the development of this complication,but several other hypotheses have been postulated.The management of diabetic neuropathic pain consists basically in excluding other causes of painful peripheral neuropathy,improving glycemic control as a prophylactic therapy and using medications to alleviate pain.First line drugs for pain relief include anticonvulsants,such as pregabalin and gabapentin and antidepressants,especial y those that act to inhibit the reuptake of serotonin and noradrenaline.In addition,there is experimental and clinical evidence that opioids can be helpful in pain control,mainly if associated with first line drugs.Other agents,including for topical application,such as capsaicin cream and lidocaine patches,have also been proposed to be useful as adjuvants in the control of diabetic neuropathic pain,but the clinical evidence is insufficient to support their use.In conclusion,a better understanding of the mechanisms underlying diabetic neuropathic pain will contribute to the search of new therapies,but also to the improvement of the guidelines to optimize pain control with the drugs currently available.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Natural Science Foundation of Jiangsu Province of China(No.BK2011630)
文摘Perilla frutescens(Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens(EOPF) attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress(CUMS)-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF(3, 6, and 9 mg·kg-1) and a positive control drug fluoxetine(20 mg·kg-1) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3rd week. Open-field test, sucrose consumption test, tail suspension test(TST), and forced swimming test(FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine(5-HT) and its metabolite, 5-hydroxyindoleacetic acid(5-HIAA), in mouse hippocampus were determined by HPLC–ECD. Serum interleukin(IL)-1, IL-6, and tumor necrosis factor(TNF)-α levels were evaluated by enzyme-linked immunosorbent assay(ELISA). The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between alteration of serotonergic responses and anti-inflammatory effects.
基金supported by the National Natural Science Foundation of China(81371488 and 81571330)
文摘Depression is the most disabling disorder world- wide that accounts for the highest proportion of global burden attributable to mental disorders. Major depressive disorder （MDD） is characterized by deep sadness, reduced energy, vegetative nervous system dysregulation, cognitive dysfunction, and even a high suicidal tendency. Although other treatment choices are available, antidepressant medication is the front-line treatment option for MDD. Regarding clinical efficacy, only - 50% of patients respond to frontline antide pressants, and 〈33% obtain remission. Currently, objective indexes to guide clinical decisions are still lacking. Further- more, knowledge about the neurobiological mechanisms underlying discrepant antidepressant outcomes is still also fragmentary. In the present review, we discuss the current research progress and clinical opinions on MDD in China.
文摘Research to date indicates that the number of coronary artery bypass graft （CABG） surgery patients affected by depression （i.e., major, minor, dysthymia） approximates between 30% and 40% of all cases. A longstanding empirical interest on psychosocial factors in CABG surgery patients highlights an association with increased risk of morbidity in the short and longer term. Recent evidence suggests that both depression and anxiety increase the risk for mortality and morbidity after CABG surgery independent of medical factors, although the behavioral and biological mechanisms are poorly understood. Though neither depression nor anxiety seem to markedly affect neuropsy- chological dysfunction, depression confers a risk for incident delirium. Following a comprehensive overview of recent literature, practical advice is described for clinicians taking into consideration possible screening aids to improve recognition of anxiety and depression among CABG surgery patients. An overview of contemporary interventions and randomized, controlled trials are described, along with suggestions for future CABG surgery research.
