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: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
To the editor:Using drugs off-label in paediatric patients(age:0-18 years)has drawn increasing attention worldwide.Off-label use of drugs implies using drugs beyond the scope of their approved market authorisation(eg,...To the editor:Using drugs off-label in paediatric patients(age:0-18 years)has drawn increasing attention worldwide.Off-label use of drugs implies using drugs beyond the scope of their approved market authorisation(eg,patient age,indication,dosage and route of administration).Previous literature reported that the prevalence of off-label drug use ranged from36.3%to 97.0%among paediatric patients worldwide.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
目的分析近十年老年抑郁领域的国内外研究进展,以期为未来老年抑郁研究提供参考。方法分别检索CNKI数据库与Web of Science核心合集2015年1月1日—2024年8月25日发表的老年抑郁相关中英文文献,运用CiteSpace、VOSviewer软件,通过作者与...目的分析近十年老年抑郁领域的国内外研究进展,以期为未来老年抑郁研究提供参考。方法分别检索CNKI数据库与Web of Science核心合集2015年1月1日—2024年8月25日发表的老年抑郁相关中英文文献,运用CiteSpace、VOSviewer软件,通过作者与机构合作网络、关键词共现网络、聚类分析、爆发词分析等方法进行文献计量学分析,并对中英文文献进行对比。结果共纳入495篇中文文献与4446篇英文文献。中文文献发文量波动小、数量少,英文文献年发文量呈缓慢上升趋势。中英文领域均形成核心作者团队与合作网络,且英文文献广度与深度更优。社会支持、药物治疗、焦虑是二者共同的热点话题,中文文献侧重特殊人群与社会因素,英文文献形成了流行病学特征、认知损害关联、危险因素、焦虑共病与干预手段等聚类。高被引文献中文以流行病学研究为主,英文多为综述与指南类。结论近十年老年抑郁领域已形成丰富的研究积累,但老年患者的特殊社会与生理特点以及更合理的治疗手段仍需进一步探讨。中文文献尚处起步阶段,需提升关注程度与体系化水平,丰富新型药物临床证据;英文文献稳步发展,需加强专属老年抑郁人群的研究。展开更多
Cannabidiol(CBD),the second most significant phytocannabinoid in the plant Cannabis sativa,which lacks potential as a drug of abuse(Viudez-Martinez et al.,2019),has gained widespread attention due to its anti-inflamma...Cannabidiol(CBD),the second most significant phytocannabinoid in the plant Cannabis sativa,which lacks potential as a drug of abuse(Viudez-Martinez et al.,2019),has gained widespread attention due to its anti-inflammatory,antioxidant,and antidepressant properties(Garci a-Gutierrez et al.,2020).Additionally,CBD exhibits neuroprotective properties,preserving neuronal viability and function by preventing or limiting cellular damage.Our team has demonstrated that CBD produces rapid antidepressant-like effects in a murine model of chronic mild stress,restoring hippocampal expression of brain-derived neurotrophic factor(BDNF).展开更多
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.
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.
基金supported by the National Natural Science Foundation of China (No.72374011).
文摘To the editor:Using drugs off-label in paediatric patients(age:0-18 years)has drawn increasing attention worldwide.Off-label use of drugs implies using drugs beyond the scope of their approved market authorisation(eg,patient age,indication,dosage and route of administration).Previous literature reported that the prevalence of off-label drug use ranged from36.3%to 97.0%among paediatric patients worldwide.
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%.
文摘目的分析近十年老年抑郁领域的国内外研究进展,以期为未来老年抑郁研究提供参考。方法分别检索CNKI数据库与Web of Science核心合集2015年1月1日—2024年8月25日发表的老年抑郁相关中英文文献,运用CiteSpace、VOSviewer软件,通过作者与机构合作网络、关键词共现网络、聚类分析、爆发词分析等方法进行文献计量学分析,并对中英文文献进行对比。结果共纳入495篇中文文献与4446篇英文文献。中文文献发文量波动小、数量少,英文文献年发文量呈缓慢上升趋势。中英文领域均形成核心作者团队与合作网络,且英文文献广度与深度更优。社会支持、药物治疗、焦虑是二者共同的热点话题,中文文献侧重特殊人群与社会因素,英文文献形成了流行病学特征、认知损害关联、危险因素、焦虑共病与干预手段等聚类。高被引文献中文以流行病学研究为主,英文多为综述与指南类。结论近十年老年抑郁领域已形成丰富的研究积累,但老年患者的特殊社会与生理特点以及更合理的治疗手段仍需进一步探讨。中文文献尚处起步阶段,需提升关注程度与体系化水平,丰富新型药物临床证据;英文文献稳步发展,需加强专属老年抑郁人群的研究。
基金supported by Instituto de Salud CarlosⅢ,Spanish Ministry of Science and Innovation,grant number PI18/00576 to MSGG and JMRRed de Investigación en Atención Primaria de Adicciones,Instituto de Salud CarlosⅢ,Spanish Ministry of Science and Innovation,grant number RD21/0009/0008 and RD24/0003/0002+1 种基金Instituto de Investigación Sanitaria y Biomédica de Alicante(ISABIAL)to JMThe Instituto de Neurociencias is a“Centre of Excellence Severo Ochoa”(CEX2021-001165-S).
文摘Cannabidiol(CBD),the second most significant phytocannabinoid in the plant Cannabis sativa,which lacks potential as a drug of abuse(Viudez-Martinez et al.,2019),has gained widespread attention due to its anti-inflammatory,antioxidant,and antidepressant properties(Garci a-Gutierrez et al.,2020).Additionally,CBD exhibits neuroprotective properties,preserving neuronal viability and function by preventing or limiting cellular damage.Our team has demonstrated that CBD produces rapid antidepressant-like effects in a murine model of chronic mild stress,restoring hippocampal expression of brain-derived neurotrophic factor(BDNF).
