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
BACKGROUND Major depressive disorder(MDD)is the most frequent reason of disabled people in the world,as reported by the World Health Organization.However,the diagnosis of MDD is mainly based on clinical symptoms.CASE ...BACKGROUND Major depressive disorder(MDD)is the most frequent reason of disabled people in the world,as reported by the World Health Organization.However,the diagnosis of MDD is mainly based on clinical symptoms.CASE SUMMARY The clinical,genetic,and molecular characteristics of two Chinese families with MDD are described in this study.There were variable ages of onset and severity in depression among the families.Both Chinese families had a very low prevalence of MDD.The mitochondrial genomes of these pedigrees were sequenced and indicated a homoplasmic T3394C(Y30H)mutation,with the polymorphism located at a highly conserved tyrosine at position 30 of ND1.The analysis also revealed unique sets of mitochondrial DNA(mtDNA)polymorphisms originating from haplogroups M9a3 and M9a.CONCLUSION This finding of the T3394C mutation in two unrelated depressed patients provides strong evidence that this mutation may have a part in the etiology of MDD.However,In these two Chinese families having the T3394C mutation,no functional mt DNA mutation was observed.Therefore,T3394C mutations are related with MDD,and the phenotypic manifestation of these mutations may be affected by changes in nuclear genes or environmental factors.展开更多
Serotonin deficiency in major depressive disorder(MDD)has formed the basis of antidepressant drug development and was originally attributed to induction of the major tryptophan(Trp)-degrading enzyme,liver Trp 2,3-diox...Serotonin deficiency in major depressive disorder(MDD)has formed the basis of antidepressant drug development and was originally attributed to induction of the major tryptophan(Trp)-degrading enzyme,liver Trp 2,3-dioxygenase(TDO),by cortisol,leading to decreased Trp availability to the brain for serotonin synthesis.Subsequently,the serotonin deficiency was proposed to involve induction of the extrahepatic Trp-degrading enzyme indoleamine 2,3-dioxygenase(IDO)by proinflammatory cytokines,with inflammation being the underlying cause.Recent evidence,however,challenges this latter concept,as not all MDD patients are immune-activated and,when present,inflammation is mild and/or transient.A wide range of antidepressant drugs inhibit the activity of liver TDO and bind specifically to the enzyme,but not to IDO.IDO induction is not a major event in MDD,but,when it occurs,its metabolic consequences may be masked and overridden by upregulation of kynurenine monooxygenase(KMO),the gateway to production of modulators of immune and neuronal functions.KMO appears to be activated in MDD by certain proinflammatory cytokines and antidepressants with anti-inflammatory properties may block this activation.We demonstrate the ability of the antidepressant ketamine to dock(bind)to KMO.The pathophysiology of MDD may be underpinned by both the serotonin deficiency and glutamatergic activation mediated respectively by TDO induction and N-methyl-D-aspartate receptor activation.Inhibition of TDO and KMO should be the focus of MDD pharmacotherapy.展开更多
BACKGROUND Major depressive disorder(MDD)is a common and serious mental illness.Many novel genes in MDD have been characterized by high-throughput methods such as microarrays or sequencing.Recently,noncoding RNAs(ncRN...BACKGROUND Major depressive disorder(MDD)is a common and serious mental illness.Many novel genes in MDD have been characterized by high-throughput methods such as microarrays or sequencing.Recently,noncoding RNAs(ncRNAs)were suggested to be involved in the complicated environmental-genetic regulatory network of MDD occurrence;however,the interplay among RNA species,including protein-coding RNAs and ncRNAs,in MDD remains unclear.AIM To investigate the RNA expression datasets downloaded from a public database and construct a network based on differentially expressed long noncoding RNA(lncRNAs),microRNAs(miRNAs),and mRNAs between MDD and controls.METHODS Gene expression data were searched in NCBI Gene Expression Omnibus using the search term“major depressive disorder.”Six array datasets from humans were related to the search term:GSE19738,GSE32280,GSE38206,GSE52790,GSE76826,and GSE81152.These datasets were processed for initial assessment and subjected to quality control and differential expression analysis.Differentially expressed lncRNAs,miRNAs,and mRNAs were determined,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed,and protein-protein interaction network was generated.The results were analyzed for their association with MDD.RESULTS After analysis,3 miRNAs,12 lncRNAs,and 33 mRNAs were identified in the competing endogenous RNA network.Two of these miRNAs were earlier shown to be involved in psychiatric disorders,and differentially expressed mRNAs were found to be highly enriched in pathways related to neurogenesis and neuroplasticity as per Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The expression of hub gene fatty acid 2-hydroxylase was enriched,and the encoded protein was found to be involved in myelin formation,indicating that neurological development and signal transduction are involved in MDD pathogenesis.CONCLUSION The present study presents candidate nc RNAs involved in the neurogenesis and neuroplasticity pathways related to MDD.展开更多
Background:Zuojin Pill(ZJP)is a classic Chinese herbal prescription with good efficacy in the treatment of Anxiety disorder(AD)and Major depressive disorder(MDD).Nevertheless,the potential mechanisms of ZJP remain unc...Background:Zuojin Pill(ZJP)is a classic Chinese herbal prescription with good efficacy in the treatment of Anxiety disorder(AD)and Major depressive disorder(MDD).Nevertheless,the potential mechanisms of ZJP remain unclear.Based on network pharmacology and molecular docking methods,this study aims to elucidate the possible mechanism of ZJP in the treatment of AD and MDD.Methods:The components and targets of Rhizoma Coptidis and Fructus Evodiae were collected from TCMSP,ETCM,HERB,SWISSADME and STITCH databases.The disease targets related to MDD and AD were collected from DISGENET,GENECARDS and OMIM databases.Protein-protein interaction network was constructed by STRING database,GO and KEGG enrichment analysis was performed by METASCAPE database,and“drugs-components-targets network”was constructed by Cytoscape software.Molecular docking verification was performed by Sailvina2.0 software.Results:ZJP may act on AKT1,IL6,TNF and other targets through caffeine,isorhamnetin,berberine and other components,regulating the Inflammatory mediator regulation of TRP channels,Serotonergic synapse,Dopaminergic synapse,PI3K/AKT signaling pathway,and other pathways.The results of molecular docking showed that berberine had the best binding activity with the core target.Conclusion:ZJP can exert anti-anxiety and anti-depression effects through multiple components,multiple targets and multiple pathways.展开更多
Major depressive disorder(MDD)is a multifactorial disorder,where multiple susceptibility genes interact with environmental factors,predisposing individuals to the development of the illness.In this article,we reviewed...Major depressive disorder(MDD)is a multifactorial disorder,where multiple susceptibility genes interact with environmental factors,predisposing individuals to the development of the illness.In this article,we reviewed different gene×environment interaction(G×E)studies shifting from a candidate gene to a genome-wide approach.Among environmental factors,childhood adversities and stressful life events have been suggested to exert crucial impacts on MDD.Importantly,the diathesis-stress conceptualization of G×E has been challenged by the differential susceptibility theory.Finally,we summarized several limitations of G×E studies and suggested how future G×E studies might reveal complex interactions between genes and environments in MDD.展开更多
Major depressive disorder is a serious and common neuropsychiatric disorder that affects more than 350 million people worldwide.Electroconvulsive therapy is the oldest and most effective treatment available for the tr...Major depressive disorder is a serious and common neuropsychiatric disorder that affects more than 350 million people worldwide.Electroconvulsive therapy is the oldest and most effective treatment available for the treatment of severe major depressive disorder.Electroconvulsive therapy modifies structural network changes in patients with major depressive disorder and schizophrenia.And it can also affect neuroinflammatory responses and may have neuroprotective effects.Electroconvulsive therapy plays an irreplaceable role in the treatment of major depressive disorder.展开更多
BACKGROUND Electroconvulsive therapy(ECT)is used to treat major depressive disorder(MDD).Relapse is often observed even after successful ECT,followed by adequate pharmaceutical treatment for MDD.AIM To investigate the...BACKGROUND Electroconvulsive therapy(ECT)is used to treat major depressive disorder(MDD).Relapse is often observed even after successful ECT,followed by adequate pharmaceutical treatment for MDD.AIM To investigate the diagnostic factors and treatment strategies associated with depression relapse.METHODS We analyzed the relationships between relapse,the diagnostic change from MDD to bipolar disorder(BP),and treatment after the initial ECT.We performed a 3-year retrospective study of the prognoses of 85 patients of the Shiga University of Medical Science Hospital.The relative risk of relapse of depressive symptoms was calculated based on the diagnostic change from MDD to BP.A receiver operating characteristic(ROC)curve was generated to evaluate the predictive accuracy of diagnostic changes from MDD to BP based on the duration between the first course of ECT and the relapse of depressive symptoms.RESULTS Eighty-five patients initially diagnosed with MDD and successfully treated with ECT were enrolled in the study.Compared with the MDD participants,more BP patients experienced relapses and required continuation and/or maintenance ECT to maintain remission(65.6%vs 15.1%,P<0.001;relative risk=4.35,95%CI:2.19-8.63,P<0.001).Twenty-nine patients experienced relapses during the three-year follow-up.In 21(72.4%,21/29)patients with relapse,the diagnosis was changed from MDD to BP.The duration from the first course of ECT to relapse was shorter for the BP patients than for the MDD patients(9.63±10.4 mo vs 3.38±3.77 mo,P=0.022);for most patients,the interval was less than one month.The relative risk of depressive symptoms based on diagnostic changes was 4.35(95%confidence interval:2.19–8.63,P<0.001),and the area under the ROC curve for detecting diagnostic changes based on relapse duration was 0.756(95%CI:0.562-0.895,P=0.007).CONCLUSION It may be beneficial to suspect BP and change the treatment strategy from MDD to BP for patients experiencing an early relapse.展开更多
BACKGROUND The use of antidepressant therapy alone has a limited efficacy in patients with childhood trauma-associated major depressive disorder(MDD).However,the effectiveness of antidepressant treatment combined with...BACKGROUND The use of antidepressant therapy alone has a limited efficacy in patients with childhood trauma-associated major depressive disorder(MDD).However,the effectiveness of antidepressant treatment combined with psychodrama in these patients is unclear.AIM To evaluate the effectiveness of antidepressant treatment combined with psychodrama.METHODS Patients with childhood trauma-associated MDD treated with antidepressants were randomly assigned to either the psychodrama intervention(observation group)or the general health education intervention(control group)and received combination treatment for 6 mo.The observation group received general health education given by the investigator together with the“semi-structured group intervention model”of Yi Shu psychodrama.A total of 46 patients were recruited,including 29 cases in the observation group and 17 cases in the control group.Symptoms of depression and anxiety as well as coping style and resting-state functional magnetic resonance imaging were assessed before and after the intervention.RESULTS Symptoms of depression and anxiety,measured by the Hamilton Depression Scale,Beck Depression Inventory,and Beck Anxiety Inventory,were reduced after the intervention in both groups of patients.The coping style of the observation group improved significantly in contrast to the control group,which did not.In addition,an interaction between treatment and time in the right superior parietal gyrus node was found.Furthermore,functional connectivity between the right superior parietal gyrus and left inferior frontal gyrus in the observation group increased after the intervention,while in the control group the connectivity decreased.CONCLUSION This study supports the use of combined treatment with antidepressants and psychodrama to improve the coping style of patients with childhood trauma-associated MDD.Functional connectivity between the superior parietal gyrus and inferior frontal gyrus was increased after this combined treatment.We speculate that psychodrama enhances the internal connectivity of the cognitive control network and corrects the negative attention bias of patients with childhood trauma-associated MDD.Elucidating the neurobiological features of patients with childhood trauma-associated MDD is important for the development of methods that can assist in early diagnosis and intervention.展开更多
BACKGROUND Major depressive disorder(MDD)tends to have a high incidence and high suicide risk.Electroconvulsive therapy(ECT)is currently a relatively effective treatment for MDD.However,the mechanism of efficacy of EC...BACKGROUND Major depressive disorder(MDD)tends to have a high incidence and high suicide risk.Electroconvulsive therapy(ECT)is currently a relatively effective treatment for MDD.However,the mechanism of efficacy of ECT is still unclear.AIM To investigate the changes in the amplitude of low-frequency fluctuations in specific frequency bands in patients with MDD after ECT.METHODS Twenty-two MDD patients and fifteen healthy controls(HCs)were recruited to this study.MDD patients received 8 ECT sessions with bitemporal placement.Resting-state functional magnetic resonance imaging was adopted to examine regional cerebellar blood flow in both the MDD patients and HCs.The MDD patients were scanned twice(before the first ECT session and after the eighth ECT session)to acquire data.Then,the amplitude of low-frequency fluctuations(ALFF)was computed to characterize the intrinsic neural oscillations in different bands(typical frequency,slow-5,and slow-4 bands).RESULTS Compared to before ECT(pre-ECT),we found that MDD patients after the eighth ECT(post-ECT)session had a higher ALFF in the typical band in the right middle frontal gyrus,posterior cingulate,right supramarginal gyrus,left superior frontal gyrus,and left angular gyrus.There was a lower ALFF in the right superior temporal gyrus.Compared to pre-ECT values,the ALFF in the slow-5 band was significantly increased in the right limbic lobe,cerebellum posterior lobe,right middle orbitofrontal gyrus,and frontal lobe in post-ECT patients,whereas the ALFF in the slow-5 band in the left sublobar region,right angular gyrus,and right frontal lobe was lower.In contrast,significantly higher ALFF in the slow-4 band was observed in the frontal lobe,superior frontal gyrus,parietal lobe,right inferior parietal lobule,and left angular gyrus.CONCLUSION Our results suggest that the abnormal ALFF in pre-and post-ECT MDD patients may be associated with specific frequency bands.展开更多
Major depressive disorder(MDD)is highly prevalent and is a significant cause of mortality and morbidity worldwide.Currently,conventional pharmacological treatments for MDD produce temporary remission in<50%of patie...Major depressive disorder(MDD)is highly prevalent and is a significant cause of mortality and morbidity worldwide.Currently,conventional pharmacological treatments for MDD produce temporary remission in<50%of patients;therefore,there is an urgent need for a wider spectrum of novel antidepressants to target newly discovered underlying disease mechanisms.Accumulated evidence has shown that immune inflammation,particularly inflammasome activity,plays an important role in the pathophysiology of MDD.In this review,we summarize the evidence on nuclear receptors(NRs),such as glucocorticoid receptor,mineralocorticoid receptor,estrogen receptor,aryl hydrocarbon receptor,and peroxisome proliferator-activated receptor,in modulating the inflammasome activity and depression-associated behaviors.This review provides evidence from an endocrine perspective to understand the role of activated NRs in the pathophysiology of MDD,and to provide insight for the discovery of antidepressants with novel mechanisms for this devastating disorder.展开更多
Objective:This study aims to identify key genes and pathways associated with the molecular biological mechanisms of major depressive disorder through bioinformatics analysis in the Gene Expression Omnibus(GEO)public d...Objective:This study aims to identify key genes and pathways associated with the molecular biological mechanisms of major depressive disorder through bioinformatics analysis in the Gene Expression Omnibus(GEO)public database of the National Center for Biotechnology Information(NCBI)website.Methods:The whole-transcriptome brain expression profile dataset(GSE101521)was obtained from the GEO database.Differentially-expressed genes(DEGs)in normal group(non-psychiatric human)and MDD group(depressive patients)were identified applying Networkanalyst online database.Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed to function annotation and enrichment analysis.After that,STRING online database was conducted to protein-protein interaction(PPI)network,and Cytoscape.3.7.2 software was performed to module analysis.Results:Out of the 41 DEGs identified from normal tissue samples and MDD,39 were upregulated and 2 were downregulated.GO enrichment analysis discovered that DEGs were primarily involved in inflammatory response,and KEGG pathway analysis suggested that the most chiefly pathway related to MDD were IL-17 signaling pathway,TNF signaling pathway and NOD-like receptor signaling pathway.Six hub genes(IL6,CXCL8,IL1B,FOS,CCL2 and CXCL2)were identified by PPI network and module analysis.Conclusion:Our current study detected novel markers and targets involved immune system,which are involved in pivotal biological mechanisms related to the pathogenesis of major depression.Looking forward,these findings still need to be validated in future experimental studies.展开更多
Integrated diagnosis,treatment and whole-course management model of major depressive disorder(MDD)is an integrated drug-psychological-physical comprehensive treatment model based on rapid biological-psychological-soci...Integrated diagnosis,treatment and whole-course management model of major depressive disorder(MDD)is an integrated drug-psychological-physical comprehensive treatment model based on rapid biological-psychological-social evaluation for treating patients with major depressive disorder.This paper comprehensively evaluates the clinical efficacy and biochemical indexes of patients,and carries out symptom evaluation,problem classification,disease diagnosis and etiological analysis of visitors from the three dimensions about physiology,psychology and society.Then,according to the symptoms and causes of different dimensions,this paper formulates personalized drug,psychological and physical therapy programs,and constantly optimizes and adjusts the treatment plan in the treatment process,so as to cure both the symptoms and the root causes,providing a reliable strategy for the treatment of clinical MDD,and establishing a standardized characteristic model for further promotion and application of this technology.At present,the project has been used in the member units of Taihe Medical Group and Shiyan City and its surrounding areas,the market response is good,and will be gradually promoted to the whole country in the later stage.展开更多
No well-established biomarkers are available for the clinical diagnosis of major depressive disorder(MDD).Vitamin D-binding protein(VDBP)is altered in plasma and postmortem dorsolateral prefrontal cortex(DLPFC)tissues...No well-established biomarkers are available for the clinical diagnosis of major depressive disorder(MDD).Vitamin D-binding protein(VDBP)is altered in plasma and postmortem dorsolateral prefrontal cortex(DLPFC)tissues of MDD patients.Thereby,the role of VDBP as a potential biomarker of MDD diagnosis was further assessed.Total extracellular vesicles(EVs)and brain cell-derived EVs(BCDEVs)were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls(HCs)in discovery(20 MDD patients and 20 HCs)and validation cohorts(88 MDD patients and 38 HCs).VDBP level in the cerebrospinal fluid(CSF)from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide(LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles(MDEVs).VDBP was significantly decreased in MDD plasma MDEVs compared to HCs,and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among BCDEVs.VDBP in plasma MDEVs was decreased both in depressed rhesus macaques and mice.A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus macaques.VDBP levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed mice.The main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.展开更多
BACKGROUND Adolescent major depressive disorder(MDD)is a significant mental health concern that often leads to recurrent depression in adulthood.Resting-state functional magnetic resonance imaging(rs-fMRI)offers uniqu...BACKGROUND Adolescent major depressive disorder(MDD)is a significant mental health concern that often leads to recurrent depression in adulthood.Resting-state functional magnetic resonance imaging(rs-fMRI)offers unique insights into the neural mechanisms underlying this condition.However,despite previous research,the specific vulnerable brain regions affected in adolescent MDD patients have not been fully elucidated.AIM To identify consistent vulnerable brain regions in adolescent MDD patients using rs-fMRI and activation likelihood estimation(ALE)meta-analysis.METHODS We performed a comprehensive literature search through July 12,2023,for studies investigating brain functional changes in adolescent MDD patients.We utilized regional homogeneity(ReHo),amplitude of low-frequency fluctuations(ALFF)and fractional ALFF(fALFF)analyses.We compared the regions of aberrant spontaneous neural activity in adolescents with MDD vs healthy controls(HCs)using ALE.RESULTS Ten studies(369 adolescent MDD patients and 313 HCs)were included.Combining the ReHo and ALFF/fALFF data,the results revealed that the activity in the right cuneus and left precuneus was lower in the adolescent MDD patients than in the HCs(voxel size:648 mm3,P<0.05),and no brain region exhibited increased activity.Based on the ALFF data,we found decreased activity in the right cuneus and left precuneus in adolescent MDD patients(voxel size:736 mm3,P<0.05),with no regions exhibiting increased activity.CONCLUSION Through ALE meta-analysis,we consistently identified the right cuneus and left precuneus as vulnerable brain regions in adolescent MDD patients,increasing our understanding of the neuropathology of affected adolescents.展开更多
Background:Major depressive disorder(MDD)has different clinical presentations in males and females.However,the neuroanatom-ical mechanisms underlying these sex differences are not fully understood.Objective:The purpos...Background:Major depressive disorder(MDD)has different clinical presentations in males and females.However,the neuroanatom-ical mechanisms underlying these sex differences are not fully understood.Objective:The purpose of present study was to explore the sex differences in brain cortical thickness(CT)and surface area(SA)of MDD and the relationship between these differences and clinical manifestations in different gender.Methods:High-resolution T1-weighted images were acquired from 61 patients with MDD and 61 healthy controls(36 females and 25 males,both).The sex differences in CT and SA were obtained using the FreeSurfer software and compared between every two groups by post hoc test.Spearman correlation analysis was also performed to explore the relationships between these regions and clinical characteristics.Results:In male patients with MDD,the CT of the right precentral was thinner compared to female patients,although this did not survive Bonferroni correction.The SA of several regions,including right superior frontal,medial orbitofrontal gyrus,inferior frontal gyrus triangle,superior temporal,middle temporal,lateral occipital gyrus,and inferior parietal lobule in female patients with MDD was smaller than that in male patients(P<0.01 after Bonferroni correction).In female patients,the SA of the right superior temporal(r=0.438,P=0.008),middle temporal(r=0.340,P=0.043),and lateral occipital gyrus(r=0.372,P=0.025)were positively correlated with illness duration.Conclusion:The current study provides evidence of sex differences in CT and SA in patients with MDD,which may improve our understanding of the sex-specific neuroanatomical changes in the development of MDD.展开更多
Background:Neuroimaging-based connectome studies have indicated that major depressive disorder(MDD)is associated with dis-rupted topological organization of large-scale brain networks.However,the disruptions and their...Background:Neuroimaging-based connectome studies have indicated that major depressive disorder(MDD)is associated with dis-rupted topological organization of large-scale brain networks.However,the disruptions and their clinical and cognitive relevance are not well established for morphological brain networks in adolescent MDD.Objective:To investigate the topological alterations of single-subject morphological brain networks in adolescent MDD.Methods:Twenty-five first-episode,treatment-naive adolescents with MDD and 19 healthy controls(HCs)underwent T1-weighted magnetic resonance imaging and a battery of neuropsychological tests.Single-subject morphological brain networks were constructed separately based on cortical thickness,fractal dimension,gyrification index,and sulcus depth,and topologically characterized by graph-based approaches.Between-group differences were inferred by permutation testing.For significant alterations,partial correla-tions were used to examine their associations with clinical and neuropsychological variables in the patients.Finally,a support vector machine was used to classify the patients from controls.Results:Compared with the HCs,the patients exhibited topological alterations only in cortical thickness-based networks character-ized by higher nodal centralities in parietal(left primary sensory cortex)but lower nodal centralities in temporal(left parabelt complex,right perirhinal ectorhinal cortex,right area PHT and right ventral visual complex)regions.Moreover,decreased nodal centralities of some temporal regions were correlated with cognitive dysfunction and clinical characteristics of the patients.These results were largely reproducible for binary and weighted network analyses.Finally,topological properties of the cortical thickness-based net-works were able to distinguish the MDD adolescents from HCs with 87.6%accuracy.Conclusion:Adolescent MDD is associated with disrupted topological organization of morphological brain networks,and the disrup-tions provide potential biomarkers for diagnosing and monitoring the disease.展开更多
Major depressive disorder(MDD),also referred to as depression,is one of the most common psychiatric disorders with a high economic burden.The etiology of depression is still not clear,but it is generally believed that...Major depressive disorder(MDD),also referred to as depression,is one of the most common psychiatric disorders with a high economic burden.The etiology of depression is still not clear,but it is generally believed that MDD is a multifactorial disease caused by the interaction of social,psychological,and biological aspects.Therefore,there is no exact pathological theory that can independently explain its pathogenesis,involving genetics,neurobiology,and neuroimaging.At present,there are many treatment measures for patients with depression,including drug therapy,psychotherapy,and neuromodulation technology.In recent years,great progress has been made in the development of new antidepressants,some of which have been applied in the clinic.This article mainly reviews the research progress,pathogenesis,and treatment of MDD.展开更多
Classic hypothalamic-pituitary-end-organ feedback loops–the hypothalamic-pituitary-adrenal axis(HPAA),hypothalamic-pituitary-thyroidal axis(HPTA),and hypothalamic-pituitary-gonadal axis(HPGA)–are associated with the...Classic hypothalamic-pituitary-end-organ feedback loops–the hypothalamic-pituitary-adrenal axis(HPAA),hypothalamic-pituitary-thyroidal axis(HPTA),and hypothalamic-pituitary-gonadal axis(HPGA)–are associated with the neuroendocrine and immune systems in major depressive disorder(MDD).Female patients with MDD present with evident neuroendocrine and immunological changes.Glucocorticoid,thyroid hormone,and reproductive steroid levels fluctuate with menstrual cycles,which might lead to glucocorticoid receptor resistance,impairment of triiodothyronine conversion,and sex hormone secretion disorders.In this review,we summarize the independent and interactive functions of these three axes in female MDD patients.The similar molecular structure of steroids implies an interrelationship between the hypothalamic-pituitary-end-organ axes and the competitive inhibitory effects at the receptor level,especially when considering the HPAA and HPGA.展开更多
Background:Transcranial alternating current stimulation(tACS)offers a new approach for adult patients with major depressive disorder(MDD).The study is to evaluate the efficacy and safety of tACS treating MDD.Methods:T...Background:Transcranial alternating current stimulation(tACS)offers a new approach for adult patients with major depressive disorder(MDD).The study is to evaluate the efficacy and safety of tACS treating MDD.Methods:This is an 8-week,double-blind,randomized,placebo-controlled study.Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min,77.5-Hz,15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks(week 4),following a 4-week observation period(week 8).The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale(HDRS-17)score≤7 at week 8.Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17,the proportion of participants having improvement in the clinical global impression-improvement,the change in HDRS-17 score(range,0-52,with higher scores indicating more depression)over the study,and variations of brain imaging and neurocognition from baseline to week 4.Safety will be assessed by vital signs at weeks 4 and 8,and adverse events will be collected during the entire study.Discussion:The tACS applied in this trial may have treatment effects on MDD with minimal side effects.Trial registration:Chinese Clinical Trial Registry,ChiCTR1800016479;http://www.chictr.org.cn/showproj.aspx?proj=22048.展开更多
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.
基金Supported by the Natural Science Foundation of Ningbo,No.2018A610292the Suzhou Key Technologies Program,No.SKY2021063+2 种基金the Jiangsu Province Social Development Project,No.BE2020764the Suzhou Clinical Medical Center for Mood Disorders,No.Szlcyxzx202109the Zhejiang Medical and Health Science and Technology Project,No.2023KY1126。
文摘BACKGROUND Major depressive disorder(MDD)is the most frequent reason of disabled people in the world,as reported by the World Health Organization.However,the diagnosis of MDD is mainly based on clinical symptoms.CASE SUMMARY The clinical,genetic,and molecular characteristics of two Chinese families with MDD are described in this study.There were variable ages of onset and severity in depression among the families.Both Chinese families had a very low prevalence of MDD.The mitochondrial genomes of these pedigrees were sequenced and indicated a homoplasmic T3394C(Y30H)mutation,with the polymorphism located at a highly conserved tyrosine at position 30 of ND1.The analysis also revealed unique sets of mitochondrial DNA(mtDNA)polymorphisms originating from haplogroups M9a3 and M9a.CONCLUSION This finding of the T3394C mutation in two unrelated depressed patients provides strong evidence that this mutation may have a part in the etiology of MDD.However,In these two Chinese families having the T3394C mutation,no functional mt DNA mutation was observed.Therefore,T3394C mutations are related with MDD,and the phenotypic manifestation of these mutations may be affected by changes in nuclear genes or environmental factors.
文摘Serotonin deficiency in major depressive disorder(MDD)has formed the basis of antidepressant drug development and was originally attributed to induction of the major tryptophan(Trp)-degrading enzyme,liver Trp 2,3-dioxygenase(TDO),by cortisol,leading to decreased Trp availability to the brain for serotonin synthesis.Subsequently,the serotonin deficiency was proposed to involve induction of the extrahepatic Trp-degrading enzyme indoleamine 2,3-dioxygenase(IDO)by proinflammatory cytokines,with inflammation being the underlying cause.Recent evidence,however,challenges this latter concept,as not all MDD patients are immune-activated and,when present,inflammation is mild and/or transient.A wide range of antidepressant drugs inhibit the activity of liver TDO and bind specifically to the enzyme,but not to IDO.IDO induction is not a major event in MDD,but,when it occurs,its metabolic consequences may be masked and overridden by upregulation of kynurenine monooxygenase(KMO),the gateway to production of modulators of immune and neuronal functions.KMO appears to be activated in MDD by certain proinflammatory cytokines and antidepressants with anti-inflammatory properties may block this activation.We demonstrate the ability of the antidepressant ketamine to dock(bind)to KMO.The pathophysiology of MDD may be underpinned by both the serotonin deficiency and glutamatergic activation mediated respectively by TDO induction and N-methyl-D-aspartate receptor activation.Inhibition of TDO and KMO should be the focus of MDD pharmacotherapy.
基金Supported by the National Key Research and Development Program of China,No.2020YFC2005500。
文摘BACKGROUND Major depressive disorder(MDD)is a common and serious mental illness.Many novel genes in MDD have been characterized by high-throughput methods such as microarrays or sequencing.Recently,noncoding RNAs(ncRNAs)were suggested to be involved in the complicated environmental-genetic regulatory network of MDD occurrence;however,the interplay among RNA species,including protein-coding RNAs and ncRNAs,in MDD remains unclear.AIM To investigate the RNA expression datasets downloaded from a public database and construct a network based on differentially expressed long noncoding RNA(lncRNAs),microRNAs(miRNAs),and mRNAs between MDD and controls.METHODS Gene expression data were searched in NCBI Gene Expression Omnibus using the search term“major depressive disorder.”Six array datasets from humans were related to the search term:GSE19738,GSE32280,GSE38206,GSE52790,GSE76826,and GSE81152.These datasets were processed for initial assessment and subjected to quality control and differential expression analysis.Differentially expressed lncRNAs,miRNAs,and mRNAs were determined,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed,and protein-protein interaction network was generated.The results were analyzed for their association with MDD.RESULTS After analysis,3 miRNAs,12 lncRNAs,and 33 mRNAs were identified in the competing endogenous RNA network.Two of these miRNAs were earlier shown to be involved in psychiatric disorders,and differentially expressed mRNAs were found to be highly enriched in pathways related to neurogenesis and neuroplasticity as per Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The expression of hub gene fatty acid 2-hydroxylase was enriched,and the encoded protein was found to be involved in myelin formation,indicating that neurological development and signal transduction are involved in MDD pathogenesis.CONCLUSION The present study presents candidate nc RNAs involved in the neurogenesis and neuroplasticity pathways related to MDD.
基金supported by National Natural Science Foundation of China(82004273)University level project of Beijing University of Traditional Chinese Medicine(2020-BUCMXJKY001)+1 种基金The sixth batch of Beijing municipal TCM experts academic experience inheritance work projectCheng Hongjie famous doctor inheritance studio,Fangshan Hospital,Beijing University of Chinese Medicine.
文摘Background:Zuojin Pill(ZJP)is a classic Chinese herbal prescription with good efficacy in the treatment of Anxiety disorder(AD)and Major depressive disorder(MDD).Nevertheless,the potential mechanisms of ZJP remain unclear.Based on network pharmacology and molecular docking methods,this study aims to elucidate the possible mechanism of ZJP in the treatment of AD and MDD.Methods:The components and targets of Rhizoma Coptidis and Fructus Evodiae were collected from TCMSP,ETCM,HERB,SWISSADME and STITCH databases.The disease targets related to MDD and AD were collected from DISGENET,GENECARDS and OMIM databases.Protein-protein interaction network was constructed by STRING database,GO and KEGG enrichment analysis was performed by METASCAPE database,and“drugs-components-targets network”was constructed by Cytoscape software.Molecular docking verification was performed by Sailvina2.0 software.Results:ZJP may act on AKT1,IL6,TNF and other targets through caffeine,isorhamnetin,berberine and other components,regulating the Inflammatory mediator regulation of TRP channels,Serotonergic synapse,Dopaminergic synapse,PI3K/AKT signaling pathway,and other pathways.The results of molecular docking showed that berberine had the best binding activity with the core target.Conclusion:ZJP can exert anti-anxiety and anti-depression effects through multiple components,multiple targets and multiple pathways.
文摘Major depressive disorder(MDD)is a multifactorial disorder,where multiple susceptibility genes interact with environmental factors,predisposing individuals to the development of the illness.In this article,we reviewed different gene×environment interaction(G×E)studies shifting from a candidate gene to a genome-wide approach.Among environmental factors,childhood adversities and stressful life events have been suggested to exert crucial impacts on MDD.Importantly,the diathesis-stress conceptualization of G×E has been challenged by the differential susceptibility theory.Finally,we summarized several limitations of G×E studies and suggested how future G×E studies might reveal complex interactions between genes and environments in MDD.
基金Supported by the Curriculum Reform Project of Taizhou University in 2021,No.xkg2021087.
文摘Major depressive disorder is a serious and common neuropsychiatric disorder that affects more than 350 million people worldwide.Electroconvulsive therapy is the oldest and most effective treatment available for the treatment of severe major depressive disorder.Electroconvulsive therapy modifies structural network changes in patients with major depressive disorder and schizophrenia.And it can also affect neuroinflammatory responses and may have neuroprotective effects.Electroconvulsive therapy plays an irreplaceable role in the treatment of major depressive disorder.
基金Supported by MHLW Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes program,No.21FA0201and MEXT/JSPS,No.17H00872.
文摘BACKGROUND Electroconvulsive therapy(ECT)is used to treat major depressive disorder(MDD).Relapse is often observed even after successful ECT,followed by adequate pharmaceutical treatment for MDD.AIM To investigate the diagnostic factors and treatment strategies associated with depression relapse.METHODS We analyzed the relationships between relapse,the diagnostic change from MDD to bipolar disorder(BP),and treatment after the initial ECT.We performed a 3-year retrospective study of the prognoses of 85 patients of the Shiga University of Medical Science Hospital.The relative risk of relapse of depressive symptoms was calculated based on the diagnostic change from MDD to BP.A receiver operating characteristic(ROC)curve was generated to evaluate the predictive accuracy of diagnostic changes from MDD to BP based on the duration between the first course of ECT and the relapse of depressive symptoms.RESULTS Eighty-five patients initially diagnosed with MDD and successfully treated with ECT were enrolled in the study.Compared with the MDD participants,more BP patients experienced relapses and required continuation and/or maintenance ECT to maintain remission(65.6%vs 15.1%,P<0.001;relative risk=4.35,95%CI:2.19-8.63,P<0.001).Twenty-nine patients experienced relapses during the three-year follow-up.In 21(72.4%,21/29)patients with relapse,the diagnosis was changed from MDD to BP.The duration from the first course of ECT to relapse was shorter for the BP patients than for the MDD patients(9.63±10.4 mo vs 3.38±3.77 mo,P=0.022);for most patients,the interval was less than one month.The relative risk of depressive symptoms based on diagnostic changes was 4.35(95%confidence interval:2.19–8.63,P<0.001),and the area under the ROC curve for detecting diagnostic changes based on relapse duration was 0.756(95%CI:0.562-0.895,P=0.007).CONCLUSION It may be beneficial to suspect BP and change the treatment strategy from MDD to BP for patients experiencing an early relapse.
文摘BACKGROUND The use of antidepressant therapy alone has a limited efficacy in patients with childhood trauma-associated major depressive disorder(MDD).However,the effectiveness of antidepressant treatment combined with psychodrama in these patients is unclear.AIM To evaluate the effectiveness of antidepressant treatment combined with psychodrama.METHODS Patients with childhood trauma-associated MDD treated with antidepressants were randomly assigned to either the psychodrama intervention(observation group)or the general health education intervention(control group)and received combination treatment for 6 mo.The observation group received general health education given by the investigator together with the“semi-structured group intervention model”of Yi Shu psychodrama.A total of 46 patients were recruited,including 29 cases in the observation group and 17 cases in the control group.Symptoms of depression and anxiety as well as coping style and resting-state functional magnetic resonance imaging were assessed before and after the intervention.RESULTS Symptoms of depression and anxiety,measured by the Hamilton Depression Scale,Beck Depression Inventory,and Beck Anxiety Inventory,were reduced after the intervention in both groups of patients.The coping style of the observation group improved significantly in contrast to the control group,which did not.In addition,an interaction between treatment and time in the right superior parietal gyrus node was found.Furthermore,functional connectivity between the right superior parietal gyrus and left inferior frontal gyrus in the observation group increased after the intervention,while in the control group the connectivity decreased.CONCLUSION This study supports the use of combined treatment with antidepressants and psychodrama to improve the coping style of patients with childhood trauma-associated MDD.Functional connectivity between the superior parietal gyrus and inferior frontal gyrus was increased after this combined treatment.We speculate that psychodrama enhances the internal connectivity of the cognitive control network and corrects the negative attention bias of patients with childhood trauma-associated MDD.Elucidating the neurobiological features of patients with childhood trauma-associated MDD is important for the development of methods that can assist in early diagnosis and intervention.
基金Supported by the Natural Science Foundation of China,No.81901373the Intelligent Medicine Research Project of Chongqing Medical University,No.ZHYX202126.
文摘BACKGROUND Major depressive disorder(MDD)tends to have a high incidence and high suicide risk.Electroconvulsive therapy(ECT)is currently a relatively effective treatment for MDD.However,the mechanism of efficacy of ECT is still unclear.AIM To investigate the changes in the amplitude of low-frequency fluctuations in specific frequency bands in patients with MDD after ECT.METHODS Twenty-two MDD patients and fifteen healthy controls(HCs)were recruited to this study.MDD patients received 8 ECT sessions with bitemporal placement.Resting-state functional magnetic resonance imaging was adopted to examine regional cerebellar blood flow in both the MDD patients and HCs.The MDD patients were scanned twice(before the first ECT session and after the eighth ECT session)to acquire data.Then,the amplitude of low-frequency fluctuations(ALFF)was computed to characterize the intrinsic neural oscillations in different bands(typical frequency,slow-5,and slow-4 bands).RESULTS Compared to before ECT(pre-ECT),we found that MDD patients after the eighth ECT(post-ECT)session had a higher ALFF in the typical band in the right middle frontal gyrus,posterior cingulate,right supramarginal gyrus,left superior frontal gyrus,and left angular gyrus.There was a lower ALFF in the right superior temporal gyrus.Compared to pre-ECT values,the ALFF in the slow-5 band was significantly increased in the right limbic lobe,cerebellum posterior lobe,right middle orbitofrontal gyrus,and frontal lobe in post-ECT patients,whereas the ALFF in the slow-5 band in the left sublobar region,right angular gyrus,and right frontal lobe was lower.In contrast,significantly higher ALFF in the slow-4 band was observed in the frontal lobe,superior frontal gyrus,parietal lobe,right inferior parietal lobule,and left angular gyrus.CONCLUSION Our results suggest that the abnormal ALFF in pre-and post-ECT MDD patients may be associated with specific frequency bands.
基金the National Natural Science Foundation of China,No.31650005.
文摘Major depressive disorder(MDD)is highly prevalent and is a significant cause of mortality and morbidity worldwide.Currently,conventional pharmacological treatments for MDD produce temporary remission in<50%of patients;therefore,there is an urgent need for a wider spectrum of novel antidepressants to target newly discovered underlying disease mechanisms.Accumulated evidence has shown that immune inflammation,particularly inflammasome activity,plays an important role in the pathophysiology of MDD.In this review,we summarize the evidence on nuclear receptors(NRs),such as glucocorticoid receptor,mineralocorticoid receptor,estrogen receptor,aryl hydrocarbon receptor,and peroxisome proliferator-activated receptor,in modulating the inflammasome activity and depression-associated behaviors.This review provides evidence from an endocrine perspective to understand the role of activated NRs in the pathophysiology of MDD,and to provide insight for the discovery of antidepressants with novel mechanisms for this devastating disorder.
基金National Natural Science Foundation of China(No.81973502)。
文摘Objective:This study aims to identify key genes and pathways associated with the molecular biological mechanisms of major depressive disorder through bioinformatics analysis in the Gene Expression Omnibus(GEO)public database of the National Center for Biotechnology Information(NCBI)website.Methods:The whole-transcriptome brain expression profile dataset(GSE101521)was obtained from the GEO database.Differentially-expressed genes(DEGs)in normal group(non-psychiatric human)and MDD group(depressive patients)were identified applying Networkanalyst online database.Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed to function annotation and enrichment analysis.After that,STRING online database was conducted to protein-protein interaction(PPI)network,and Cytoscape.3.7.2 software was performed to module analysis.Results:Out of the 41 DEGs identified from normal tissue samples and MDD,39 were upregulated and 2 were downregulated.GO enrichment analysis discovered that DEGs were primarily involved in inflammatory response,and KEGG pathway analysis suggested that the most chiefly pathway related to MDD were IL-17 signaling pathway,TNF signaling pathway and NOD-like receptor signaling pathway.Six hub genes(IL6,CXCL8,IL1B,FOS,CCL2 and CXCL2)were identified by PPI network and module analysis.Conclusion:Our current study detected novel markers and targets involved immune system,which are involved in pivotal biological mechanisms related to the pathogenesis of major depression.Looking forward,these findings still need to be validated in future experimental studies.
基金Supported by Grants from the National Key R&D Program of China (2018YFC1314600)the 2021 Shiyan City Guidance Project (21Y33)
文摘Integrated diagnosis,treatment and whole-course management model of major depressive disorder(MDD)is an integrated drug-psychological-physical comprehensive treatment model based on rapid biological-psychological-social evaluation for treating patients with major depressive disorder.This paper comprehensively evaluates the clinical efficacy and biochemical indexes of patients,and carries out symptom evaluation,problem classification,disease diagnosis and etiological analysis of visitors from the three dimensions about physiology,psychology and society.Then,according to the symptoms and causes of different dimensions,this paper formulates personalized drug,psychological and physical therapy programs,and constantly optimizes and adjusts the treatment plan in the treatment process,so as to cure both the symptoms and the root causes,providing a reliable strategy for the treatment of clinical MDD,and establishing a standardized characteristic model for further promotion and application of this technology.At present,the project has been used in the member units of Taihe Medical Group and Shiyan City and its surrounding areas,the market response is good,and will be gradually promoted to the whole country in the later stage.
基金supported by the National Natural Science Key Foundation of China(No.81830040 and 82130042 to ZJ Zhang)China Science and Technology Innovation 2030-Major Project(China)(No.2022ZD0211701,2022ZD0211700 and 2021ZD0200700 to ZJ Zhang)+2 种基金Science and Technology Program of Guangdong,China(No.2018B030334001 to ZJ Zhang)Science and Technology Program of Shenzhen,China(No.GJHZ20210705141400002,KCXFZ20211020164543006,JCYJ20220818101615033 and ZDSYS20220606100606014 to ZJ Zhang)The National Natural Science Foundation of China(No.U20A6005 to ZQM).
文摘No well-established biomarkers are available for the clinical diagnosis of major depressive disorder(MDD).Vitamin D-binding protein(VDBP)is altered in plasma and postmortem dorsolateral prefrontal cortex(DLPFC)tissues of MDD patients.Thereby,the role of VDBP as a potential biomarker of MDD diagnosis was further assessed.Total extracellular vesicles(EVs)and brain cell-derived EVs(BCDEVs)were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls(HCs)in discovery(20 MDD patients and 20 HCs)and validation cohorts(88 MDD patients and 38 HCs).VDBP level in the cerebrospinal fluid(CSF)from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide(LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles(MDEVs).VDBP was significantly decreased in MDD plasma MDEVs compared to HCs,and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among BCDEVs.VDBP in plasma MDEVs was decreased both in depressed rhesus macaques and mice.A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus macaques.VDBP levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed mice.The main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.
基金Supported by The 2024 Guizhou Provincial Health Commission Science and Technology Fund Project,No.gzwkj2024-47502022 Provincial Clinical Key Specialty Construction Project。
文摘BACKGROUND Adolescent major depressive disorder(MDD)is a significant mental health concern that often leads to recurrent depression in adulthood.Resting-state functional magnetic resonance imaging(rs-fMRI)offers unique insights into the neural mechanisms underlying this condition.However,despite previous research,the specific vulnerable brain regions affected in adolescent MDD patients have not been fully elucidated.AIM To identify consistent vulnerable brain regions in adolescent MDD patients using rs-fMRI and activation likelihood estimation(ALE)meta-analysis.METHODS We performed a comprehensive literature search through July 12,2023,for studies investigating brain functional changes in adolescent MDD patients.We utilized regional homogeneity(ReHo),amplitude of low-frequency fluctuations(ALFF)and fractional ALFF(fALFF)analyses.We compared the regions of aberrant spontaneous neural activity in adolescents with MDD vs healthy controls(HCs)using ALE.RESULTS Ten studies(369 adolescent MDD patients and 313 HCs)were included.Combining the ReHo and ALFF/fALFF data,the results revealed that the activity in the right cuneus and left precuneus was lower in the adolescent MDD patients than in the HCs(voxel size:648 mm3,P<0.05),and no brain region exhibited increased activity.Based on the ALFF data,we found decreased activity in the right cuneus and left precuneus in adolescent MDD patients(voxel size:736 mm3,P<0.05),with no regions exhibiting increased activity.CONCLUSION Through ALE meta-analysis,we consistently identified the right cuneus and left precuneus as vulnerable brain regions in adolescent MDD patients,increasing our understanding of the neuropathology of affected adolescents.
基金supported by the Sichuan Science and Technology Program (No.2018]Y0666)58th batch Chinese Postdoctoral Science Foundation (No.2015M582554)+4 种基金sichuan Provincial Health and Family Planning Commission (No.150251)Science and Technology Bureau of Yibin city (No.2015SF030)Open Project of Sichuan Key Laboratory of Functional and Molecular Imaging (No.SCU-HM-2021001)Project of Health Commission of Yibin city (No.2020YW085)Xinglin Scholar Project of Chengdu University of Taditional Chinese Medicine (No.YYZX2020111).
文摘Background:Major depressive disorder(MDD)has different clinical presentations in males and females.However,the neuroanatom-ical mechanisms underlying these sex differences are not fully understood.Objective:The purpose of present study was to explore the sex differences in brain cortical thickness(CT)and surface area(SA)of MDD and the relationship between these differences and clinical manifestations in different gender.Methods:High-resolution T1-weighted images were acquired from 61 patients with MDD and 61 healthy controls(36 females and 25 males,both).The sex differences in CT and SA were obtained using the FreeSurfer software and compared between every two groups by post hoc test.Spearman correlation analysis was also performed to explore the relationships between these regions and clinical characteristics.Results:In male patients with MDD,the CT of the right precentral was thinner compared to female patients,although this did not survive Bonferroni correction.The SA of several regions,including right superior frontal,medial orbitofrontal gyrus,inferior frontal gyrus triangle,superior temporal,middle temporal,lateral occipital gyrus,and inferior parietal lobule in female patients with MDD was smaller than that in male patients(P<0.01 after Bonferroni correction).In female patients,the SA of the right superior temporal(r=0.438,P=0.008),middle temporal(r=0.340,P=0.043),and lateral occipital gyrus(r=0.372,P=0.025)were positively correlated with illness duration.Conclusion:The current study provides evidence of sex differences in CT and SA in patients with MDD,which may improve our understanding of the sex-specific neuroanatomical changes in the development of MDD.
基金supported by the Key-Area Research and Development Program of Guangdong Province (No.2019B030335001)National Natural Science Foundation of China (Nos.81922036)+1 种基金Key Realm R&D Program of Guangzhou (No.202007030005)Natural Science Foundation of Guangdong Province (2021A1515010746).
文摘Background:Neuroimaging-based connectome studies have indicated that major depressive disorder(MDD)is associated with dis-rupted topological organization of large-scale brain networks.However,the disruptions and their clinical and cognitive relevance are not well established for morphological brain networks in adolescent MDD.Objective:To investigate the topological alterations of single-subject morphological brain networks in adolescent MDD.Methods:Twenty-five first-episode,treatment-naive adolescents with MDD and 19 healthy controls(HCs)underwent T1-weighted magnetic resonance imaging and a battery of neuropsychological tests.Single-subject morphological brain networks were constructed separately based on cortical thickness,fractal dimension,gyrification index,and sulcus depth,and topologically characterized by graph-based approaches.Between-group differences were inferred by permutation testing.For significant alterations,partial correla-tions were used to examine their associations with clinical and neuropsychological variables in the patients.Finally,a support vector machine was used to classify the patients from controls.Results:Compared with the HCs,the patients exhibited topological alterations only in cortical thickness-based networks character-ized by higher nodal centralities in parietal(left primary sensory cortex)but lower nodal centralities in temporal(left parabelt complex,right perirhinal ectorhinal cortex,right area PHT and right ventral visual complex)regions.Moreover,decreased nodal centralities of some temporal regions were correlated with cognitive dysfunction and clinical characteristics of the patients.These results were largely reproducible for binary and weighted network analyses.Finally,topological properties of the cortical thickness-based net-works were able to distinguish the MDD adolescents from HCs with 87.6%accuracy.Conclusion:Adolescent MDD is associated with disrupted topological organization of morphological brain networks,and the disrup-tions provide potential biomarkers for diagnosing and monitoring the disease.
基金This review was supported by the National Basic Research Development Program of China(2016YFC1307100)the National Natural Science Foundation of China(81930033 and 81771465+6 种基金81401127)Shanghai Key Project of Science&Technology(2018SHZDZX05)Shanghai Jiao Tong University Medical Engineering Foundation(YG2016MS48)Shanghai Jiao Tong University School of Medicine(19XJ11006)the Sanming Project of Medicine in Shenzhen Municipality(SZSM201612006)the National Key Technologies R&D Program of China(2012BAI01B04)the Innovative Research Team of High-level Local Universities in Shanghai.
文摘Major depressive disorder(MDD),also referred to as depression,is one of the most common psychiatric disorders with a high economic burden.The etiology of depression is still not clear,but it is generally believed that MDD is a multifactorial disease caused by the interaction of social,psychological,and biological aspects.Therefore,there is no exact pathological theory that can independently explain its pathogenesis,involving genetics,neurobiology,and neuroimaging.At present,there are many treatment measures for patients with depression,including drug therapy,psychotherapy,and neuromodulation technology.In recent years,great progress has been made in the development of new antidepressants,some of which have been applied in the clinic.This article mainly reviews the research progress,pathogenesis,and treatment of MDD.
基金the National Key Research and Development Program of China(2016YFC1307100,2016YFC1307105)the National Natural Science Foundation of China(81771465,81930033)+6 种基金the National Key Technologies R&D Program of China(2012BAI01B04)Shanghai Key Project of Science and Technology(2018SHZDZX05)the Sanming Project of Medicine in Shenzheng(SZSM201612006)Shanghai Key Medicine Specialties Program(ZK2019A06)Shanghai Clinical Research Center for Mental Health(SCRC-MH,19MC1911100)the Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission(20204Y0025)the Innovative Research Team of High-level Local Universities in Shanghai,and the National Health System“Good Doctor”Construction Project of Yangpu District of Shanghai Municipality(2020-2023).
文摘Classic hypothalamic-pituitary-end-organ feedback loops–the hypothalamic-pituitary-adrenal axis(HPAA),hypothalamic-pituitary-thyroidal axis(HPTA),and hypothalamic-pituitary-gonadal axis(HPGA)–are associated with the neuroendocrine and immune systems in major depressive disorder(MDD).Female patients with MDD present with evident neuroendocrine and immunological changes.Glucocorticoid,thyroid hormone,and reproductive steroid levels fluctuate with menstrual cycles,which might lead to glucocorticoid receptor resistance,impairment of triiodothyronine conversion,and sex hormone secretion disorders.In this review,we summarize the independent and interactive functions of these three axes in female MDD patients.The similar molecular structure of steroids implies an interrelationship between the hypothalamic-pituitary-end-organ axes and the competitive inhibitory effects at the receptor level,especially when considering the HPAA and HPGA.
基金This work is supported by the National Key R&D Program of China(No.2017YFC1310001)the National Natural Science Foundation of China(No.81771862)+2 种基金the Beijing Municipal Science and Technology Project(No.Z171100000117016)the Beijing Natural Science Foundation(No.KZ201710025017)the Beijing Hundred,Thousand,and Ten Thousand Talents Project(No.2017-CXYF-09).
文摘Background:Transcranial alternating current stimulation(tACS)offers a new approach for adult patients with major depressive disorder(MDD).The study is to evaluate the efficacy and safety of tACS treating MDD.Methods:This is an 8-week,double-blind,randomized,placebo-controlled study.Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min,77.5-Hz,15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks(week 4),following a 4-week observation period(week 8).The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale(HDRS-17)score≤7 at week 8.Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17,the proportion of participants having improvement in the clinical global impression-improvement,the change in HDRS-17 score(range,0-52,with higher scores indicating more depression)over the study,and variations of brain imaging and neurocognition from baseline to week 4.Safety will be assessed by vital signs at weeks 4 and 8,and adverse events will be collected during the entire study.Discussion:The tACS applied in this trial may have treatment effects on MDD with minimal side effects.Trial registration:Chinese Clinical Trial Registry,ChiCTR1800016479;http://www.chictr.org.cn/showproj.aspx?proj=22048.
