Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods ...Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.展开更多
BACKGROUND Aortic coarctation is a potentially fatal condition that is primarily treated surgically.Despite successful procedures,patients frequently experience postoperative anxiety and depression,which can hinder re...BACKGROUND Aortic coarctation is a potentially fatal condition that is primarily treated surgically.Despite successful procedures,patients frequently experience postoperative anxiety and depression,which can hinder recovery and worsen outcomes.Pharmacological interventions,such as 5-hydroxytryptamine(5-HT)and norepinephrine reuptake inhibitors,are commonly prescribed;however,their efficacy alone or in combination with non-invasive brain stimulation techniques,such as repetitive transcranial magnetic stimulation(TMS),remains unclear.AIM To assess the effect of medications and TMS on post-aortic surgery anxiety and depression.METHODS We analyzed the outcomes of 151 patients with anxiety and depression who were hospitalized for aortic dissection between January 2020 and September 2022.Using the random number table method,75 and 76 patients were allocated to the normal control and study groups,respectively.All the patients were treated using routine procedures.The control group was administered anti-anxiety and antidepression drugs,whereas the study group was treated with TMS in addition to these medications.The patients in both groups showed improvement after two courses of treatment.The Hamilton Anxiety Scale(HAMA)and the Hamilton Depression Scale(HAMD)were used to assess anxiety and depression,respectively.The serum levels of brain-derived neurotrophic factor(BDNF)and 5-HT were determined using enzyme-linked immunosorbent assay.The Pittsburgh Sleep Quality Index(PSQI)was used to estimate sleep quality,and the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)was used to assess cognitive function.RESULTS The HAMD and HAMA scores reduced in 2 groups,with the study group achieving a lower level than control(P<0.05).In the control group,43 patients recovered,17 showed improvement,and 15 were deemed invalid.In the study group,52 recovered,20 improved,and four were invalid.The efficacy rate in study group was 94.74%compared to 80.00%in control(P<0.05).The BDNF and 5-HT levels increased in both groups,with higher levels observed in the experimental group(P<0.05).Moreover,the PSQI scores decreased in 2 groups,but were lower in the intervention group than control(P<0.05).The scores of the RBANS items increased,with the study group scoring higher than control(P<0.05).CONCLUSION Combining anti-anxiety and anti-depressive drugs with repetitive TMS after aortic surgery may enhance mood and treatment outcomes,offering a promising clinical approach.展开更多
BACKGROUND Depression is strongly associated with colorectal cancer(CRC).Few bibliometric analyses have systematically summarized the research focus and recent progress in this field.AIM To determine the research stat...BACKGROUND Depression is strongly associated with colorectal cancer(CRC).Few bibliometric analyses have systematically summarized the research focus and recent progress in this field.AIM To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between CRC and depression.METHODS Articles on depression in CRC patients were collected from the Web of Science Core Collection.CiteSpace and VOSviewer software were used to visualize bibliometric networks.RESULTS From 2001 to 2022,Supportive Care in Cancer,the United States,Tilburg University,and Mols were the most productive and influential journal,country,institution,and author name.Co-occurrence cluster analysis of keywords placed quality of life,anxiety,and psychological stress in the center of the visual network diagram.Further clustering was performed for the clusters with studies of the relevant mechanism of action,which showed that:(1)Cytokines have a role essential for the occurrence and development of depressive disorders in CRC;(2)MicroRNAs have a role essential for the development of depressive disorders in CRC;(3)Some anticancer drugs have pro-depressant activity;and(4)Selective serotonin reuptake inhibitors have both antitumor and antidepressant activity.CONCLUSION Life quality and psychological nursing of the cancer population were key topics.The roles of cytokines and microRNAs,the pro-depression activity of anticancer drugs and their antitumor properties deserve in-depth study.展开更多
Parkinson's disease(PD) is one of the most prevalent neurodegenerative diseases which typically affects individuals over 65 years. Although the symptomatology is predominantly motor, neuropsychiatric manifestation...Parkinson's disease(PD) is one of the most prevalent neurodegenerative diseases which typically affects individuals over 65 years. Although the symptomatology is predominantly motor, neuropsychiatric manifestations, e.g., depression, apathy, anxiety, and cognitive impairment occur in the course of the illness and can have a great impact on the quality of life in these patients. Parkinson's disease is commonly comorbid with depression with prevalence rates of depression, generally higher than those reported in general population. Depression in PD is frequently underestimated andconsequently undertreated, which have significant effects on the quality of life in these patients. The neurobiology of depression in PD is complex and involves alterations in dopaminergic, serotonergic, noradrenergic and possibly other neurotransmitter systems which are affected in the course of the disease. The tricyclic antidepressants and the selective serotonin reuptake inhibitors are the two classes of antidepressant drugs used for depressive symptoms in PD. Several published studies suggested that both classes are of comparable efficacy. Other serotonergic antidepressants, e.g., nefazodone and trazodone have also been of benefit. Meanwhile, there are limited data available on other drugs but these suggest a benefit from the serotonin and noradrenaline reuptake inhibitors such as mirtazapine, venlafaxine, atomoxetine and duloxetine. Some of the drugs used in symptomatic treatment of PD, e.g., the irreversible selective inhibitors of the enzyme monoamine oxidase-B, rasagiline and selegiline as well as the dopamine receptor agonist pramipexole are likely to have direct antidepressant activity independent of their motor improving action. This would make these drugs an attractive option in depressed subjects with PD. The aim of this review is to provide an updated data on the prevalence, clinical features of depression in subjects with PD. The effects of antiparkinsonian and antidepressant drugs on depressive symptoms in these patients are also discussed.展开更多
We previously showed that death-associated protein kinase 1(DAPK1)expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's d...We previously showed that death-associated protein kinase 1(DAPK1)expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's disease.In addition,depression is a risk factor for developing Alzheimer's disease,as well as an early clinical manifestation of Alzheimer's disease.Meanwhile,cognitive dysfunction is a distinctive feature of major depressive disorder.Therefore,DAPK1 may be related to cognitive dysfunction in major depressive disorder.In this study,we established a mouse model of major depressive disorder by housing mice individually and exposing them to chronic,mild,unpredictable stressors.We found that DAPK1 and tau protein levels were increased in the hippocampal CA3 area,and tau was hyperphosphorylated at Thr231,Ser262,and Ser396 in these mice.Furthermore,DAPK1 shifted from axonal expression to overexpression on the cell membrane.Exercise and treatment with the antidepressant drug citalopram decreased DAPK1 expression and tau protein phosphorylation in hippocampal tissue and improved both depressive symptoms and cognitive dysfunction.These results indicate that DAPK1 may be a potential reason and therapeutic target of cognitive dysfunction in major depressive disorder.展开更多
目的通过采集行为学和脑电数据,考察重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)对首发抑郁症患者的疗效及对执行功能的影响,初步探讨rTMS治疗抑郁症患者潜在的认知神经影响的机制。方法采用随机数字表法将首...目的通过采集行为学和脑电数据,考察重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)对首发抑郁症患者的疗效及对执行功能的影响,初步探讨rTMS治疗抑郁症患者潜在的认知神经影响的机制。方法采用随机数字表法将首发抑郁症患者分为试验组(n=26)和对照组(n=25),试验组患者进行8周的rTMS联合药物治疗,对照组患者仅进行单纯药物治疗。于干预前和干预后采用汉密尔顿抑郁量表24(24-item Hamilton depression rating scale,HAMD-24)、汉密尔顿焦虑量表14(14-item Hamilton anxiety rating scale,HAMA-14)以及行为学工具和事件相关电位(event-related potential,ERP)评估患者的抑郁焦虑状态和执行功能的变化。结果两组抑郁症患者治疗后的HAMD-24评分和HAMA-14评分较干预前均显著下降(P均<0.001),且试验组患者HAMD-24评分显著低于对照组(P<0.05)。Go/Nogo任务中,两组抑郁症患者Nogo条件正确应答数较干预前均明显提升(P均<0.05);Stroop任务中,试验组抑郁症患者不一致条件的正确应答数较干预前明显提升,不一致条件反应时较干预前明显变短,且试验组抑郁症患者不一致条件的正确应答数较对照组明显提升、不一致条件反应时明显变短(P均<0.05)。脑电指标中,试验组抑郁症患者干预后较干预前诱发了更大的Nogo N2波幅和P3波幅(P均<0.05);试验组抑郁症患者的N2差异波波幅和P3差异波波幅显著大于对照组(P均<0.05)。结论rTMS可以加强抑郁症患者的认知神经活动水平,提升执行功能,对抑郁症患者抑郁症状的治疗效果更好。展开更多
基于抑郁症相关医学文献信息挖掘潜在抗抑郁药并揭示其抗抑郁相关机制和通路,为抑郁症药物的研发提供方向。通过SemRep提取与抑郁症相关的语义三元组,限定语义关系和语义类型确定潜在药物。从PubChem、GeneCards等数据库获取潜在药物和...基于抑郁症相关医学文献信息挖掘潜在抗抑郁药并揭示其抗抑郁相关机制和通路,为抑郁症药物的研发提供方向。通过SemRep提取与抑郁症相关的语义三元组,限定语义关系和语义类型确定潜在药物。从PubChem、GeneCards等数据库获取潜在药物和抑郁症的靶点并取二者的交集后,构建交集靶点的蛋白相互作用(protein-protein interaction,PPI)网络。通过Cytoscape分析PPI网络,确定核心靶点。通过R软件对核心靶点进行GO(gene ontology)和KEGG(kyoto encyclopedia of genes and genomes)分析。最后,通过AutodockTool软件对核心靶点与潜在药物进行分子对接分析。结果表明Hydrocortisone、Benzodiazepine、Curcumin、Metformin、Nicotine、Risperidone等6种药物为潜在抗抑郁药,这些药物通过炎症、神经递质的调节等生物过程以及MAPK(mitogen activated protein kinase)、TNF(tumor necrosis factor)等信号通路发挥抗抑郁作用,并且与抑郁症核心靶点间结合性能良好。此外,Benzodiazepine和Nicotine在临床实践中存在成瘾和滥用的风险,在抑郁症治疗中的作用可能有限。可见基于语义三元组和网络药理学发现抑郁症药物新知识,可以节约时间和经济成本,也能为临床药物使用提供新的方向。展开更多
基金supported by Natural Science Foundation of Shandong ProvinceChina[ZR2022MH115]the National Natural Science Foundation of China[81301479,82202593]。
文摘Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.
文摘BACKGROUND Aortic coarctation is a potentially fatal condition that is primarily treated surgically.Despite successful procedures,patients frequently experience postoperative anxiety and depression,which can hinder recovery and worsen outcomes.Pharmacological interventions,such as 5-hydroxytryptamine(5-HT)and norepinephrine reuptake inhibitors,are commonly prescribed;however,their efficacy alone or in combination with non-invasive brain stimulation techniques,such as repetitive transcranial magnetic stimulation(TMS),remains unclear.AIM To assess the effect of medications and TMS on post-aortic surgery anxiety and depression.METHODS We analyzed the outcomes of 151 patients with anxiety and depression who were hospitalized for aortic dissection between January 2020 and September 2022.Using the random number table method,75 and 76 patients were allocated to the normal control and study groups,respectively.All the patients were treated using routine procedures.The control group was administered anti-anxiety and antidepression drugs,whereas the study group was treated with TMS in addition to these medications.The patients in both groups showed improvement after two courses of treatment.The Hamilton Anxiety Scale(HAMA)and the Hamilton Depression Scale(HAMD)were used to assess anxiety and depression,respectively.The serum levels of brain-derived neurotrophic factor(BDNF)and 5-HT were determined using enzyme-linked immunosorbent assay.The Pittsburgh Sleep Quality Index(PSQI)was used to estimate sleep quality,and the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)was used to assess cognitive function.RESULTS The HAMD and HAMA scores reduced in 2 groups,with the study group achieving a lower level than control(P<0.05).In the control group,43 patients recovered,17 showed improvement,and 15 were deemed invalid.In the study group,52 recovered,20 improved,and four were invalid.The efficacy rate in study group was 94.74%compared to 80.00%in control(P<0.05).The BDNF and 5-HT levels increased in both groups,with higher levels observed in the experimental group(P<0.05).Moreover,the PSQI scores decreased in 2 groups,but were lower in the intervention group than control(P<0.05).The scores of the RBANS items increased,with the study group scoring higher than control(P<0.05).CONCLUSION Combining anti-anxiety and anti-depressive drugs with repetitive TMS after aortic surgery may enhance mood and treatment outcomes,offering a promising clinical approach.
文摘BACKGROUND Depression is strongly associated with colorectal cancer(CRC).Few bibliometric analyses have systematically summarized the research focus and recent progress in this field.AIM To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between CRC and depression.METHODS Articles on depression in CRC patients were collected from the Web of Science Core Collection.CiteSpace and VOSviewer software were used to visualize bibliometric networks.RESULTS From 2001 to 2022,Supportive Care in Cancer,the United States,Tilburg University,and Mols were the most productive and influential journal,country,institution,and author name.Co-occurrence cluster analysis of keywords placed quality of life,anxiety,and psychological stress in the center of the visual network diagram.Further clustering was performed for the clusters with studies of the relevant mechanism of action,which showed that:(1)Cytokines have a role essential for the occurrence and development of depressive disorders in CRC;(2)MicroRNAs have a role essential for the development of depressive disorders in CRC;(3)Some anticancer drugs have pro-depressant activity;and(4)Selective serotonin reuptake inhibitors have both antitumor and antidepressant activity.CONCLUSION Life quality and psychological nursing of the cancer population were key topics.The roles of cytokines and microRNAs,the pro-depression activity of anticancer drugs and their antitumor properties deserve in-depth study.
文摘Parkinson's disease(PD) is one of the most prevalent neurodegenerative diseases which typically affects individuals over 65 years. Although the symptomatology is predominantly motor, neuropsychiatric manifestations, e.g., depression, apathy, anxiety, and cognitive impairment occur in the course of the illness and can have a great impact on the quality of life in these patients. Parkinson's disease is commonly comorbid with depression with prevalence rates of depression, generally higher than those reported in general population. Depression in PD is frequently underestimated andconsequently undertreated, which have significant effects on the quality of life in these patients. The neurobiology of depression in PD is complex and involves alterations in dopaminergic, serotonergic, noradrenergic and possibly other neurotransmitter systems which are affected in the course of the disease. The tricyclic antidepressants and the selective serotonin reuptake inhibitors are the two classes of antidepressant drugs used for depressive symptoms in PD. Several published studies suggested that both classes are of comparable efficacy. Other serotonergic antidepressants, e.g., nefazodone and trazodone have also been of benefit. Meanwhile, there are limited data available on other drugs but these suggest a benefit from the serotonin and noradrenaline reuptake inhibitors such as mirtazapine, venlafaxine, atomoxetine and duloxetine. Some of the drugs used in symptomatic treatment of PD, e.g., the irreversible selective inhibitors of the enzyme monoamine oxidase-B, rasagiline and selegiline as well as the dopamine receptor agonist pramipexole are likely to have direct antidepressant activity independent of their motor improving action. This would make these drugs an attractive option in depressed subjects with PD. The aim of this review is to provide an updated data on the prevalence, clinical features of depression in subjects with PD. The effects of antiparkinsonian and antidepressant drugs on depressive symptoms in these patients are also discussed.
基金supported by the Department of Science and Technology of Henan Province,Nos.192102310084(to HCZ),222102310143(to DXD)the Youth Fund of School of Basic Medical Sciences of Zhengzhou University,No.JCYXY2017-YQ-07(to DXD)。
文摘We previously showed that death-associated protein kinase 1(DAPK1)expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's disease.In addition,depression is a risk factor for developing Alzheimer's disease,as well as an early clinical manifestation of Alzheimer's disease.Meanwhile,cognitive dysfunction is a distinctive feature of major depressive disorder.Therefore,DAPK1 may be related to cognitive dysfunction in major depressive disorder.In this study,we established a mouse model of major depressive disorder by housing mice individually and exposing them to chronic,mild,unpredictable stressors.We found that DAPK1 and tau protein levels were increased in the hippocampal CA3 area,and tau was hyperphosphorylated at Thr231,Ser262,and Ser396 in these mice.Furthermore,DAPK1 shifted from axonal expression to overexpression on the cell membrane.Exercise and treatment with the antidepressant drug citalopram decreased DAPK1 expression and tau protein phosphorylation in hippocampal tissue and improved both depressive symptoms and cognitive dysfunction.These results indicate that DAPK1 may be a potential reason and therapeutic target of cognitive dysfunction in major depressive disorder.
文摘目的通过采集行为学和脑电数据,考察重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)对首发抑郁症患者的疗效及对执行功能的影响,初步探讨rTMS治疗抑郁症患者潜在的认知神经影响的机制。方法采用随机数字表法将首发抑郁症患者分为试验组(n=26)和对照组(n=25),试验组患者进行8周的rTMS联合药物治疗,对照组患者仅进行单纯药物治疗。于干预前和干预后采用汉密尔顿抑郁量表24(24-item Hamilton depression rating scale,HAMD-24)、汉密尔顿焦虑量表14(14-item Hamilton anxiety rating scale,HAMA-14)以及行为学工具和事件相关电位(event-related potential,ERP)评估患者的抑郁焦虑状态和执行功能的变化。结果两组抑郁症患者治疗后的HAMD-24评分和HAMA-14评分较干预前均显著下降(P均<0.001),且试验组患者HAMD-24评分显著低于对照组(P<0.05)。Go/Nogo任务中,两组抑郁症患者Nogo条件正确应答数较干预前均明显提升(P均<0.05);Stroop任务中,试验组抑郁症患者不一致条件的正确应答数较干预前明显提升,不一致条件反应时较干预前明显变短,且试验组抑郁症患者不一致条件的正确应答数较对照组明显提升、不一致条件反应时明显变短(P均<0.05)。脑电指标中,试验组抑郁症患者干预后较干预前诱发了更大的Nogo N2波幅和P3波幅(P均<0.05);试验组抑郁症患者的N2差异波波幅和P3差异波波幅显著大于对照组(P均<0.05)。结论rTMS可以加强抑郁症患者的认知神经活动水平,提升执行功能,对抑郁症患者抑郁症状的治疗效果更好。
文摘基于抑郁症相关医学文献信息挖掘潜在抗抑郁药并揭示其抗抑郁相关机制和通路,为抑郁症药物的研发提供方向。通过SemRep提取与抑郁症相关的语义三元组,限定语义关系和语义类型确定潜在药物。从PubChem、GeneCards等数据库获取潜在药物和抑郁症的靶点并取二者的交集后,构建交集靶点的蛋白相互作用(protein-protein interaction,PPI)网络。通过Cytoscape分析PPI网络,确定核心靶点。通过R软件对核心靶点进行GO(gene ontology)和KEGG(kyoto encyclopedia of genes and genomes)分析。最后,通过AutodockTool软件对核心靶点与潜在药物进行分子对接分析。结果表明Hydrocortisone、Benzodiazepine、Curcumin、Metformin、Nicotine、Risperidone等6种药物为潜在抗抑郁药,这些药物通过炎症、神经递质的调节等生物过程以及MAPK(mitogen activated protein kinase)、TNF(tumor necrosis factor)等信号通路发挥抗抑郁作用,并且与抑郁症核心靶点间结合性能良好。此外,Benzodiazepine和Nicotine在临床实践中存在成瘾和滥用的风险,在抑郁症治疗中的作用可能有限。可见基于语义三元组和网络药理学发现抑郁症药物新知识,可以节约时间和经济成本,也能为临床药物使用提供新的方向。
