Objective Elevated depressive symptoms are well-documented among geriatric adults with cardiovascular disease(CVD);however,few studies have accounted for long-term cumulative depressive symptom exposure.This study det...Objective Elevated depressive symptoms are well-documented among geriatric adults with cardiovascular disease(CVD);however,few studies have accounted for long-term cumulative depressive symptom exposure.This study determined the relationship between cumulative depressive symptoms and CVD.Methods Individual participant data were obtained from the China Health and Retirement Longitudinal Study(CHARLS)and Health and Retirement Study(HRS).Eligible participants had access to assessment information on depressive symptoms and had no history of CVD at baseline.Long-term cumulative depressive symptoms were estimated by calculating the area under the curve based on the Center for Epidemiological Studies Depression Scale.Results Herein,8,861 participants from CHARLS(mean age:58.58 years;male:48.6%)and 7,284 from HRS(60.94 years;35.0%)were enrolled.The median follow-up period was 5 years for the CHARLS and10 years for the HRS.Compared with the first quartile of cumulative depressive symptoms,the HRs(95%CI)in the fourth quartile were 1.73(1.48,2.02)for predicting CVD(P<0.001),1.83(1.52,2.19)for heart disease(P<0.001),1.53(95%CI:1.17,1.99)for stroke(P=0.002)in CHARLS.For HRS,the HRs(95%CI)were 1.41(95%CI:1.27,1.57;P<0.001),1.42(95%CI:1.26,1.59;P<0.001),and 1.30(95%CI:1.06,1.58;P=0.010)respectively.Strong dose-response relationships were observed,with similar results for the two cohorts.Conclusion Long-term cumulative depressive symptoms were significantly associated with incident CVD in middle-aged and older adults,providing insights into controlling long-term depressive symptoms to improve this cohort's health.展开更多
BACKGROUND Non-suicidal self-injury(NSSI)is common among adolescents with depressive disorders and poses a major public health challenge.Rumination,a key cognitive feature of depression,includes different subtypes tha...BACKGROUND Non-suicidal self-injury(NSSI)is common among adolescents with depressive disorders and poses a major public health challenge.Rumination,a key cognitive feature of depression,includes different subtypes that may relate to NSSI through distinct psychological mechanisms.However,how these subtypes interact with specific NSSI behaviors remains unclear.AIM To examine associations between rumination subtypes and specific NSSI behaviors in adolescents.METHODS We conducted a cross-sectional study with 305 hospitalized adolescents diagnosed with depressive disorders.The subjects ranged from 12-18 years in age.Rumi-nation subtypes were assessed using the Ruminative Response Scale,and 12 NSSI behaviors were evaluated using a validated questionnaire.Network analysis was applied to explore symptom-level associations and identify central symptoms.RESULTS The network analysis revealed close connections between rumination subtypes and NSSI behaviors.Brooding was linked to behaviors such as hitting objects and burning.Scratching emerged as the most influential NSSI symptom.Symptomfocused rumination served as a key bridge connecting rumination and NSSI.CONCLUSION Symptom-focused rumination and scratching were identified as potential intervention targets.These findings highlight the psychological significance of specific cognitive-behavioral links in adolescent depression and suggest directions for tailored prevention and treatment.However,the cross-sectional,single-site design limits causal inference and generalizability.Future longitudinal and multi-center studies are needed to confirm causal pathways and verify the generalizability of the findings to broader adolescent populations.展开更多
Clinically differentiating bipolarⅡdisorder(BD-Ⅱ)from major depressive disorder(MDD)remains a significant challenge in modern psychiatry.These two conditions share substantial clinical symptomatology,making accurate...Clinically differentiating bipolarⅡdisorder(BD-Ⅱ)from major depressive disorder(MDD)remains a significant challenge in modern psychiatry.These two conditions share substantial clinical symptomatology,making accurate diagnosis difficult in routine clinical practice.Misdiagnosis may lead to inappropriate treatment strategies,increased psychological and physical burdens,reduced quality of life,and impaired social functioning.Genetic overlap may partially explain the clinical similarities between MDD and BD-Ⅱ,and biomarkers along with neuroimaging techniques are receiving increasing attention as tools to aid in diagnosis.For example,electroencephalography has been shown to effectively distinguish between unipolar depression and bipolar depression;serum levels of glycogen synthase kinase-3 have also been investigated as a potential tool for differentiating between the two disorders.A comprehensive assessment integrating clinical characteristics,genetic basis research,and multimodal evaluations using neuroimaging and biomarkers through a multidisciplinary approach will help enhance clinicians'ability to distinguish between MDD and BD-Ⅱ.By improving diagnostic accuracy,more personalized and effective treatment strategies can be developed,ultimately improving patients'health outcomes and quality of life.展开更多
Background Dynamic interpersonal therapy(DIT)is a short-term psychodynamic psychotherapy that has been shown to effectively reduce depressive symptoms in patients with major depressive disorder(MDD).In DIT,the depress...Background Dynamic interpersonal therapy(DIT)is a short-term psychodynamic psychotherapy that has been shown to effectively reduce depressive symptoms in patients with major depressive disorder(MDD).In DIT,the depressive symptoms are formulated as responses to impaired mentalisation.DIT aims to alleviate depressive symptoms by improving mentalising.Aims This study aimed to examine the effect of DIT on improving mentalising and the mediating effect of mentalising in changes in depressive symptoms.Methods Outpatients received either DIT combined with antidepressant medication treatment(DIT group)or antidepressant medication treatment alone(ADM group)for 16 weeks.The Hamilton Depression Rating Scale(HAMD),Patient Health Questionnaire(PHQ)and Reflective Functioning Questionnaire(RFQ)were used.The intention-to-treat principle,mixed linear models,multiple imputation,Pearson's correlation analysis and mediation analysis were conducted.The per-protocol principle was used as sensitivity analysis.Results The DIT group had significantly lower HAMD(least-squares(LS)mean difference=-3.756,p<0.001),PHQ(LS mean difference=-4.188,p<0.001),uncertainty about mental states in the RFQ(RFQ-U,LS mean difference=-2.116,p<0.001)and higher certainty about mental states in the RFQ(RFQ-C,LS mean difference=2.214,p=0.028)scores than the ADM group at post-treatment.The change in RFQ-C was marginally significantly correlated with the change in HAMD(r=-0.218,poretao=0.090),The change in RFQ-U was significantly correlated with the change in HAMD(r=-0.269,poroco-0.024)and the change in PHQ(r=-0.43,Peoretceo l<e0.001).When using RFQ-U as the mediating variable and PHQ as the dependent variable,a significant mediating effect was found(p=0.043,95% confidence interval 0.024 to 1.453).Conclusions The DIT group yielded better outcomes compared with the ADM group in reducing depressive symptoms and improving mentalising.Improvements in mentalising were associated with reductions in depressive symptoms.These findings support that mentalising may contribute to the therapeutic effects of DIT in MDD.展开更多
BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly unders...BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly understood.AIM To examine regional abnormalities in spontaneous brain activity among patients with MDD-OB comorbidity.METHODS This study adopted a regional homogeneity(ReHo)analysis of resting-state functional magnetic resonance imaging.The study included 149 hospital patients divided into four groups:Patients experiencing their first episode of drug-naive MDD with OB,patients with MDD without OB,and age-and sex-matched healthy individuals with and without OB.Whole-brain ReHo analysis was conducted using SPM12 software and RESTplus toolkits,with group comparisons via ANOVA and post-hoc tests.Correlations between ReHo values and behavioral measures were examined.RESULTS ANOVA revealed significant whole-brain ReHo differences among the four groups in four key regions:The left middle temporal gyrus(MTG.L),right cuneus,left precuneus,and left thalamus.Post-hoc analyses confirmed pairwise differences between all groups across these regions(P<0.05).OB was associated with ReHo alterations in the MTG.L,right cuneus,and left thalamus,whereas abnormalities in the precuneus suggested synergistic pathological mechanisms between MDD and OB.Statistically significant correlations were found between the drive and fun-seeking dimensions of the behavioral activation system,as well as behavioral inhibition and the corresponding ReHo values.CONCLUSION Our findings provide novel evidence for the neuroadaptive mechanisms underlying the MDD-OB comorbidity.Further validation could lead to personalized interventions targeting MTG.L hyperactivity and targeting healthy food cues.展开更多
BACKGROUND Sensitivity to stress is essential in the onset,clinical symptoms,course,and prognosis of major depressive disorder(MDD).Meanwhile,it was unclear how variously classified but connected stress-sensitivity va...BACKGROUND Sensitivity to stress is essential in the onset,clinical symptoms,course,and prognosis of major depressive disorder(MDD).Meanwhile,it was unclear how variously classified but connected stress-sensitivity variables affect MDD.We hypothesize that high-level trait-and state-related stress-sensitivity factors may have different cumulative effects on the clinical symptoms and follow-up outcomes of MDD.AIM To investigate how stress-sensitivity factors added up and affected MDD clinical symptoms and follow-up results.METHODS In this prospective study,281 MDD patients were enrolled from a tertiary care setting.High-level stress-sensitivity factors were classified as trait anxiety,state anxiety,perceived stress,and neuroticism,with a total score in the top quartile of the research cohort.The cumulative effects of stress-sensitivity factors on cognitive dysfunction,disability and functional impairment,suicide risk,and depressive and anxiety symptoms were examined using an analysis of variance with linear trend analysis.Correlations were investigated further using multiple regression analysis.RESULTS Regarding high-level stress-sensitivity factors,53.40%of patients had at least one at baseline,and 29.61%had two or more.Four high-level stress-sensitivity components had significant cumulative impacts on MDD symptoms at baseline(all P<0.001).Perceived stress predicted the greatest effect sizes of state-related factors on depressive symptoms(partialη^(2)=0.153;standardizedβ=0.195;P<0.05).The follow-up outcomes were significantly impacted only by the high-level trait-related components,mainly when it came to depressive symptoms and suicide risk,which were predicted by trait anxiety and neuroticism,respectively(partialη^(2)=0.204 and 0.156;standardizedβ=0.247 and 0.392;P<0.05).CONCLUSION To enhance outcomes of MDD and lower the suicide risk,screening for stress-sensitivity factors and considering multifaceted measures,mainly focusing on trait-related ones,should be addressed clinically.展开更多
Background Mental disorders rank among the leading contributors to the global disease burden, with depressive disorders being among the most prevalent.Aims The objective of this study is to examine the prevalence, inc...Background Mental disorders rank among the leading contributors to the global disease burden, with depressive disorders being among the most prevalent.Aims The objective of this study is to examine the prevalence, incidence and years lived with disability (YLDs) associated with depressive disorders, particularly major depressive disorder and dysthymia, in Iran from 1990 to 2021. To achieve this, the research focused on analysing these metrics across various dimensions, including temporal trends, sex differences, age categories and subnational regions.Methods The data used in this study are sourced directly from the Institute for Health Metrics and Evaluation, ensuring that the information is both authoritative and reliable. All-age count estimates and age-standardised rates (per 100 000) were calculated for prevalence, incidence and YLDs. The disease burden indicators were analysed for the period spanning from 1990 to 2021, stratified by sex, age and location. The percentage change between 1990 and 2021 was also documented. The 95% uncertainty interval (UI) was reported for each of the reported estimates.Results The prevalence of depressive disorders in Iran demonstrated a notable upward trend from 1990 to 2021, with the rate of growth being particularly pronounced within the country. The age-standardised prevalence rate per 100 000 individuals for depressive disorders in Iran was 5609 (95% UI 4810 to 6488). By 2021, the number of depression cases in Iran reached 5.2 million, which is approximately 2.37 times the figure reported in 1990. The prevalence of depressive disorders was notably higher among females compared with males. The age-standardised prevalence rate per 100 000 individuals for males was 4184 (95% UI 3545 to 4929). For females, this figure was significantly greater, reaching 7077 (95% UI 6115 to 8172). Out of the total reported cases of depressive disorders in Iran, 3.2 million were observed in females, while males accounted for 2 million cases.Conclusions The findings highlighted the considerable impact of depressive disorders in Iran, both nationally and regionally, while also revealing variations across sex and age groups. Given the shifts in the demographic structure and the growing burden of these disorders, it is essential to prioritise screening initiatives, education programmes and strategies aimed at enhancing mental health awareness and ensuring improved access to mental health services in health policy planning.展开更多
Background GW117(N-(2-(6-chloro-7-deuteromethoxynaphthalen-1-yl)ethyl)acetamide)is a dual-acting agent(MT1/MT2 agonist,5-HT_(2C)antagonist)with prior evidence of antidepressant efficacy and favourable safety.Aims To p...Background GW117(N-(2-(6-chloro-7-deuteromethoxynaphthalen-1-yl)ethyl)acetamide)is a dual-acting agent(MT1/MT2 agonist,5-HT_(2C)antagonist)with prior evidence of antidepressant efficacy and favourable safety.Aims To preliminarily evaluate the efficacy and safety of GW117 in major depressive disorder(MDD)and to explore the optimal dosing.Methods A total of 280 eligible patients aged 18-65years with MDD were randomly assigned(1:1:1:1)to8 weeks of double-blind treatment with fixed doses of GW117 tablets(20,40,60 mg/day)or placebo.The primary endpoint was the change from baseline to Week 8 in the total score of the Hamilton Rating Scale for Depression-17item(HAMD-17).Key secondary endpoints included changes in the Montgomery-?sberg Depression Rating Scale(MADRS)total score over the same period.Results In the full analysis set(n=276),GW117 showed numerically greater reductions versus placebo in the HAMD-17 and MADRS total scores,as well as higher response rates at Week 8.However,these differences did not reach statistical significance,potentially due to a high placebo response and other contributing factors.In a post hoc analysis of an optimal subgroup(baseline HAMD-17>24 or insomnia factor>4),GW117 showed efficacy in improving multidimensional symptoms,including insomnia.The 20 mg dose demonstrated a significant3.66-point greater reduction in MADRS(p=0.026)and a23.16%higher response rate(p=0.013)compared with placebo.GW117 was well-tolerated,with no cases of alanine aminotransferase or aspartate aminotransferase exceeding 3×the upper limit of normal and no concerning safety signals reported.Conclusions This exploratory study found that GW117demonstrated encouraging antidepressant efficacy and a favourable safety profile in patients with MDD.Although differences versus placebo did not reach statistical significance in the overall population,GW11720 mg monotherapy showed significant improvements in multidimensional depressive symptoms,including insomnia,in the optimal response subgroup.No hepatotoxicity was reported,supporting its promising therapeutic potential for further clinical development.展开更多
Background Biomarkers for predicting suicide risk in hospitalised patients with mental disorders have been understudied.Currently,suicide risk assessment tools based on objective indicators are limited in China.Aims T...Background Biomarkers for predicting suicide risk in hospitalised patients with mental disorders have been understudied.Currently,suicide risk assessment tools based on objective indicators are limited in China.Aims To examine the value of various biomarkers in suicide risk prediction and develop a risk assessment model with clinical utility using machine learning.Methods This cohort study analysed patients with major depressive disorder(MDD) who were hospitalised for the first time between January 2016 and March 2023 from four specialised mental health institutions.A total of 139 features,including biomarker measurements,medical orders and psychological scales,were assessed for analysis.Their suicide risk was evaluated by qualified nurses using Nurse s Global Assessment of Suicide Risk within 1 week after admission.Five machine learning models were trained with 10-fold cross-validation across three hospitals and were externally validated in an independent cohort.The primary performance was assessed using the area under the receiver operating characteristic curve(AUROC).The model was interpreted using the SHapley Additive exPlanations(SHAP) analysis.Biomarker importance was evaluated by comparing model performance with and without these biomarkers.Results Of 3143 patients with MDD included in this study,the incidence of high suicide risk within 1 week after first admission was 660(21.0%).Among all models,the Extreme Gradient Boosting can more effectively predict future risks,with an AUROC higher than 0.8(p<0.001).The SHAP values identified the 10 most important features,including five biomarkers.After clustering analysis,electroconvulsive therapy,physical restraint,β2-microglobulin and triiodothyronine were found to have heterogeneous effects on suicide risk.Combining biomarkers with other data from electronic health records significantly improved the performance and clinical utility of machine learning models based on demographics,diagnosis,laboratory tests,medical orders and psychological scales.Conclusions This study demonstrates the potential for a biomarker-based suicide risk assessment for patients with MDD,emphasising the interaction between biomarkers and therapeutic interventions.展开更多
Major depressive disorder(MDD),a psychiatric disorder characterized by functional brain deficits,poses considerable diagnostic and treatment challenges,especially in adolescents owing to varying clinical presentations...Major depressive disorder(MDD),a psychiatric disorder characterized by functional brain deficits,poses considerable diagnostic and treatment challenges,especially in adolescents owing to varying clinical presentations.Biomarkers hold substantial clinical potential in the field of mental health,enabling objective assessments of physiological and pathological states,facilitating early diagnosis,and enhancing clinical decision-making and patient outcomes.Recent breakthroughs combine neuroimaging with machine learning(ML)to distinguish brain activity patterns between MDD patients and healthy controls,paving the way for diagnostic support and personalized treatment.However,the accuracy of the results depends on the selection of neuroimaging features and algorithms.Ensuring privacy protection,ML model accuracy,and fostering trust are essential steps prior to clinical implementation.Future research should prioritize the establishment of comprehensive legal frameworks and regulatory mechanisms for using ML in MDD diagnosis while safeguarding patient privacy and rights.By doing so,we can advance accuracy and personalized care for MDD.展开更多
Background Yueju Pill,a classic traditional Chinese medicine,shows antidepressant effects rapidly.However,biomarkers that can predict its treatment outcomes in major depressive disorder(MDD)are still lacking.Multimoda...Background Yueju Pill,a classic traditional Chinese medicine,shows antidepressant effects rapidly.However,biomarkers that can predict its treatment outcomes in major depressive disorder(MDD)are still lacking.Multimodal magnetic resonance imaging(MRI)offers a promising avenue to identify such biomarkers.Aims This pilot study aimed to explore whether therapeutic responses to Yueju Pill could be predicted by MRI-derived brain networks and to identify drug-specific biomarkers in comparison to escitalopram,a mainstream antidepressant.Methods We collected multimodal MRI data and blood samples from 28 outpatients with MDD from the Fourth People's Hospital of Taizhou,who were randomly divided into two groups to receive either Yueju Pill(23 g/time/day)or escitalopram(10 mg,two times a day)for 4 days.Morphological and functional brain networks were constructed and used to predict individual changes in symptoms quantified by the 24-item Hamilton Depression Scale(HAMD-24)scores and serum brain-derived neurotrophic factor(BDNF)levels.Results After the treatment,both groups exhibited significant reductions in the HAMD-24 scores,while only the Yueju Pill group showed significant increases in the BDNF levels.Gyrification Index-based morphological networks predicted change rates of the HAMD-24 scores in both groups,but sulcus depth-based and cortical thickness-based morphological networks predicted change rates of the HAMD-24 scores and BDNF levels,respectively,only in the Yueju Pill group.Subnetwork analyses revealed that the visual network independently predicted the changes in both the HAMD-24 scores(sulcus depth-based networks)and BDNF levels(cortical thickness-based networks)following Yueju Pill treatment.Conclusions Morphological but not functional brain networks can predict symptom improvement and BDNF changes of patients with MDD after Yueju Pill treatment.Sulcus depth-based and cortical thickness-based morphological brain networks,particularly their visual subnetworks,might serve as Yueju Pill-specific biomarkers for predicting the therapeutic responses.These findings have the potential to guide personalised therapy for patients with MDD early in the therapeutic process.展开更多
Background Numerous studies have consistently demonstrated that a considerable proportion of patients with major depressive disorder (MDD) frequently exhibit pronounced dyslipidaemia. However, the causal dynamics betw...Background Numerous studies have consistently demonstrated that a considerable proportion of patients with major depressive disorder (MDD) frequently exhibit pronounced dyslipidaemia. However, the causal dynamics between MDD and dyslipidaemia remain elusive.Aims To comprehensively disentangle the genetic causality between MDD and various phenotypes of blood lipids, thereby facilitating the advancement of management strategies for these conditions.Methods We conducted a two-sample univariable Mendelian randomisation (MR) analysis using different models, including the inverse variance weighted (IVW) method and causal analysis using the summary effect (CAUSE) estimates, as well as a multivariable MR analysis. This analysis used summary statistics from genome-wide association studies (GWAS) of MDD and five lipid traits: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, total cholesterol and triglycerides (TG), encompassing 5 237 893 individuals of European and East Asian ancestries. For MDD, a total of 598 701 individuals were included, with 500 199 individuals of European ancestry (Ncase=170 756, Ncontrol=329 443) and 98 502 of East Asian ancestry (Ncase=12 588, Ncontrol=85 914). Lipid data were collected from 4 639 192 individuals through the Global Lipids Genetics Consortium (European, N=4 096 085;East Asian, N=543 107). Next, we used the two-step MR to explore the mediating factors between MDD and TG, and the risk factors affecting TG through MDD. Finally, we conducted a GWAS meta-analysis and enrichment analysis.Results In univariable MR, we observed a negative causal effect of low-density lipoprotein on MDD in both European populations (IVW: odds ratio (OR): 0.972, 95% confidence interval (CI) 0.947 to 0.998, p=0.037) and East Asian populations (IVW: OR: 0.928, 95% CI 0.864 to 0.997, p=0.042). Additionally, we identified a bidirectional causal relationship between TG and MDD, with TG having a causal effect on MDD (IVW: OR: 1.052, 95% CI 1.020 to 1.085, p=0.001) and MDD having a causal effect on TG (IVW: OR: 1.075, 95% CI 1.047 to 1.104, p<0.001). Multivariable MR analysis further supported the role of TG in MDD (OR: 1.205, 95% CI 1.034 to 1.405, p=0.017). CAUSE estimates indicated that the causal model of MDD on TG provided a better fit than the sharing model (p=0.003), while the association of TG on MDD was more likely due to horizontal correlated pleiotropy than causality. Mediation analyses revealed that waist-hip ratio (WHR) mediated 69% of the total causal effect of MDD on TG, while other identified risk factors exhibited lower mediating proportions either mediated through MDD (≤17%) or originating from MDD (≤29%). The GWAS meta-analysis highlighted potential pathways related to lipid processes and nucleosome assembling, with significant cell types identified in brain regions and liver tissues.Conclusions The findings indicate that genetic proxies of MDD are associated with elevated levels of TG, with WHR serving as a clinical indicator of the association. This suggests that interventions targeting WHR may be effective in reducing TG levels in patients with MDD.展开更多
Background Metabolic dysregulation has been implicated in major depressive disorder(MDD).Aims We aimed to explore the potential role of plasma metabolites in MDD.Methods We conducted Mendelian randomisation(MR)analysi...Background Metabolic dysregulation has been implicated in major depressive disorder(MDD).Aims We aimed to explore the potential role of plasma metabolites in MDD.Methods We conducted Mendelian randomisation(MR)analysis to evaluate the causal effects of 871 circulating metabolites on MDD,using the Genome-Wide Association Studies datasets of MDD(N=1035760)and metabolites(N=8299).Bayesian colocalisation and druggability analyses were employed to identify genetic variants contributing to both MDD and levels of metabolites in plasma and to pinpoint metabolites with therapeutic potential,respectively.Results MR analysis identified 11 metabolites associated with MDD(false discovery rate<0.05).Eight metabolites,including arachidonate(20:4n6)(odds ratio(OR):0.97),1-arachidonoyl-GPC(20:4n6)(OR:0.98),1-(1-enylpalmitoyl)-2-palmitoleoyl-GPC(P-16:0/16:1)(OR:0.97),succinoyltaurine(OR:0.98),3-methoxycatechol sulphate(1)(OR:0.98)and 11β-hydroxyandrosterone glucuronide(OR:0.97),showed protective effects against MDD.Three metabolites were associated with increased risk,namely,butyrylglycine(OR:1.03),3-carboxy-4-methyl-5-propyl-2-furanpropanoate(OR:1.02)and 1-(1-enyl-stearoyl)-2-oleoyl-GPE(P-18:0/18:1)(OR:1.02).Colocalisation analysis supported shared genetic signals between five lipid metabolites and MDD,particularly at loci harbouring FADS and ATP9A.Notably,a majority of metabolites associated with MDD are being explored as therapeutic targets for various psychiatric disorders.Conclusions Genetically predicted levels of certain circulating metabolites make a causal contribution to MDD.Further investigation of their roles may provide novel pathophysiological insights and give clues for targeted therapies.展开更多
Background The patient-reported Dimensional Anhedonia Rating Scale(DARS)has been adapted into Chinese,so there is a need to evaluate its measurement properties in a Chinese population.Aims To evaluate the reliability ...Background The patient-reported Dimensional Anhedonia Rating Scale(DARS)has been adapted into Chinese,so there is a need to evaluate its measurement properties in a Chinese population.Aims To evaluate the reliability and validity of the DARS among Chinese individuals with major depressive disorder(MDD)and its treatment sensitivity in a prospective clinical study.Methods Data were from a multicentre,prospective clinical study(NCT03294525),which recruited both patients with MDD,who were followed for 8 weeks,and healthy controls(HCs),assessed at baseline only.The analysis included confirmatory factor analysis,validity and sensitivity to change.Results Patients’mean(standard deviation(SD))age was 34.8(11.0)years,with 68.7%being female.75.2%of patients with MDD had melancholic features,followed by 63.8%with anxious distress.Patients had experienced MDD for a mean(SD)of 9.2(18)months.DARS scores covered the full range of severity with no major floor or ceiling effects.Confirmatory factor analysis showed adequate fit statistics(comparative fit index 0.976,goodness-of-fit index 0.935 and root mean square error of approximation 0.055).Convergent validity with anhedonia-related measures was confirmed.While the correlation between the DARS and the Hamilton Depression Rating Scale was not strong(r=0.31,baseline),the DARS was found to differentiate between levels of depression.Greater improvements in DARS scores were seen with the Hamilton Rating Scale for Depression responder group(effect size 1.16)compared with the non-responder group(effect size 0.46).Conclusions This study comprehensively evaluated the measurement properties of the DARS using a Chinese population with MDD.Overall,the Chinese version of DARS demonstrates good psychometric properties and has been found to be responsive to change during antidepressant treatment.The DARS is a suitable scale for assessing patient-reported anhedonia in future clinical trials.展开更多
BACKGROUND Childhood maltreatment has a potentially lasting influence on subthreshold depressive symptoms(SDS)and major depressive disorder(MDD).This study aimed to explore the association of childhood maltreatment wi...BACKGROUND Childhood maltreatment has a potentially lasting influence on subthreshold depressive symptoms(SDS)and major depressive disorder(MDD).This study aimed to explore the association of childhood maltreatment with MDD and SDS,focusing on the differences between young and middle-aged adults.AIMTo examine the associations among childhood maltreatment, SDS, and MDD in young and middle-aged adults.METHODSA total of 3209 adults were recruited from 34 primary healthcare settings. The Childhood Trauma Questionnaire-28item Short Form was used to assess childhood maltreatment. The Patient Health Questionnaire-9 was used toassess SDS and the Mini-International Neuropsychiatric Interview depression module was used to assess MDD.RESULTSChildhood maltreatment was significantly associated with higher odds of developing SDS and MDD than in thenon-depressed control group (P < 0.05). Childhood maltreatment significantly increased the risk of developing SDSin young adults but was not significantly associated with SDS in middle-aged adults (P = 0.055). Conversely,childhood maltreatment was significantly associated with MDD in both young (P < 0.001) and middle-aged adults(P < 0.05). In young adults, various types of childhood maltreatment were associated with MDD;however, onlyemotional abuse and neglect were significantly associated with MDD in middle-aged adults.CONCLUSIONOur study revealed a strong association among childhood maltreatment, SDS, and MDD across age groups,highlighting the impact of emotional abuse and need for trauma-informed depression care.展开更多
In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release f...In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.展开更多
BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affectin...BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affecting work and interpersonal communication,increasing the risk of recurrence,and adding to the burden on families.Studying the influencing factors of their social function is of great significance.AIM To explore the social function score and its influencing factors in patients with residual depressive symptoms.METHODS This observational study surveyed patients with residual depressive symptoms(case group)and healthy patients undergoing physical examinations(control group).Participants were admitted between January 2022 and December 2023.Social functioning was assessed using the Sheehan Disability Scale(SDS),and scores were compared between groups.Factors influencing SDS scores in patients with residual depressive symptoms were analyzed by applying multiple linear regression while using the receiver operating characteristic curve,and these RESULTS The SDS scores of the 158 patients with depressive symptoms were 11.48±3.26.Compared with the control group,the SDS scores and all items in the case group were higher.SDS scores were higher in patients with relapse,discon-tinuous medication,drug therapy alone,severe somatic symptoms,obvious residual symptoms,and anxiety scores≥8.Disease history,medication compliance,therapy method,and residual symptoms correlated positively with SDS scores(r=0.354,0.414,0.602,and 0.456,respectively).Independent influencing factors included disease history,medication compliance,therapy method,somatic symptoms,residual symptoms,and anxiety scores(P<0.05).The areas under the curve for predicting social functional impairment using these factors were 0.713,0.559,0.684,0.729,0.668,and 0.628,respectively,with sensitivities of 79.2%,61.8%,76.8%,81.7%,63.6%,and 65.5%and specificities of 83.3%,87.5%,82.6%,83.3%,86.7%,and 92.1%,respectively.CONCLUSION The social function scores of patients with residual symptoms of depression are high.They are affected by disease history,medication compliance,therapy method,degree of somatic symptoms,residual symptoms,and anxiety.展开更多
INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depres...INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depression leads to social and occupational impairment,diminished quality of life and an elevated risk of death by suicide.展开更多
BACKGROUND Research has consistently demonstrated that patients with major depressive disorder(MDD)exhibit attentional switching dysfunction,and the dual-task paradigm has emerged as a valuable tool for probing cognit...BACKGROUND Research has consistently demonstrated that patients with major depressive disorder(MDD)exhibit attentional switching dysfunction,and the dual-task paradigm has emerged as a valuable tool for probing cognitive deficits.However,the neuroelectrophysiological mechanism underlying this deficit has not been clarified.AIM To investigate the event-related potential(ERP)characteristics of attentional switching dysfunction and further explore the neuroelectrophysiological mechanism of the cognitive processing deficits underlying attentional switching dysfunction in MDD.METHODS The participants included 29 MDD patients and 29 healthy controls(HCs).The ERPs of the participants were measured while they performed the dual-task para digm.The behavioral and ERP N100,P200,P300,and late positive potential(LPP)data were analyzed.RESULTS This study revealed greater accuracy in HCs and slower reaction times(RTs)in MDD patients.Angry facial pictures led to lower accuracy.The results also revealed shorter RTs for happy facial pictures and the longest RTs for the 500-ms stimulus onset asynchrony.With respect to ERP characteristics,happy facial pictures and neutral facial pictures evoked higher amplitudes.The N100,P200,P300,and LPP amplitudes at Pz were the highest.MDD patients had lower P200 mean amplitudes and LPP amplitudes than HCs did.CONCLUSION In conclusion,MDD patients exhibited abnormal ERP characteristics evoked by the dual-task paradigm,which could be the neural correlates of the known abnormalities in attentional switching in patients with MDD.These results provide valuable insights into the understanding of the neural mechanisms of attentional switching function and may guide targeted interventions in patients with MDD.展开更多
BACKGROUND Major depressive disorder(MDD)with comorbid anxiety is an intricate psychiatric condition,but limited research is available on the degree centrality(DC)between anxious MDD and nonanxious MDD patients.AIM To...BACKGROUND Major depressive disorder(MDD)with comorbid anxiety is an intricate psychiatric condition,but limited research is available on the degree centrality(DC)between anxious MDD and nonanxious MDD patients.AIM To examine changes in DC values and their use as neuroimaging biomarkers in anxious and non-anxious MDD patients.METHODS We examined 23 anxious MDD patients,30 nonanxious MDD patients,and 28 healthy controls(HCs)using the DC for data analysis.RESULTS Compared with HCs,the anxious MDD group reported markedly reduced DC values in the right fusiform gyrus(FFG)and inferior occipital gyrus,whereas elevated DC values in the left middle frontal gyrus and left inferior parietal angular gyrus.The nonanxious MDD group exhibited surged DC values in the bilateral cerebellum IX,right precuneus,and opercular part of the inferior frontal gyrus.Unlike the nonanxious MDD group,the anxious MDD group exhibited declined DC values in the right FFG and bilateral calcarine(CAL).Besides,declined DC values in the right FFG and bilateral CAL negatively correlated with anxiety scores in the MDD group.CONCLUSION This study shows that abnormal DC patterns in MDD,especially in the left CAL,can distinguish MDD from its anxiety subtype,indicating a potential neuroimaging biomarker.展开更多
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2021A1515011629)Construction of High-level University of Guangdong(G623330580and G621331128)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(2019)。
文摘Objective Elevated depressive symptoms are well-documented among geriatric adults with cardiovascular disease(CVD);however,few studies have accounted for long-term cumulative depressive symptom exposure.This study determined the relationship between cumulative depressive symptoms and CVD.Methods Individual participant data were obtained from the China Health and Retirement Longitudinal Study(CHARLS)and Health and Retirement Study(HRS).Eligible participants had access to assessment information on depressive symptoms and had no history of CVD at baseline.Long-term cumulative depressive symptoms were estimated by calculating the area under the curve based on the Center for Epidemiological Studies Depression Scale.Results Herein,8,861 participants from CHARLS(mean age:58.58 years;male:48.6%)and 7,284 from HRS(60.94 years;35.0%)were enrolled.The median follow-up period was 5 years for the CHARLS and10 years for the HRS.Compared with the first quartile of cumulative depressive symptoms,the HRs(95%CI)in the fourth quartile were 1.73(1.48,2.02)for predicting CVD(P<0.001),1.83(1.52,2.19)for heart disease(P<0.001),1.53(95%CI:1.17,1.99)for stroke(P=0.002)in CHARLS.For HRS,the HRs(95%CI)were 1.41(95%CI:1.27,1.57;P<0.001),1.42(95%CI:1.26,1.59;P<0.001),and 1.30(95%CI:1.06,1.58;P=0.010)respectively.Strong dose-response relationships were observed,with similar results for the two cohorts.Conclusion Long-term cumulative depressive symptoms were significantly associated with incident CVD in middle-aged and older adults,providing insights into controlling long-term depressive symptoms to improve this cohort's health.
基金Supported by Key Research and Development Program of Shaanxi Province,China,No.2024SF-YBXM-078.
文摘BACKGROUND Non-suicidal self-injury(NSSI)is common among adolescents with depressive disorders and poses a major public health challenge.Rumination,a key cognitive feature of depression,includes different subtypes that may relate to NSSI through distinct psychological mechanisms.However,how these subtypes interact with specific NSSI behaviors remains unclear.AIM To examine associations between rumination subtypes and specific NSSI behaviors in adolescents.METHODS We conducted a cross-sectional study with 305 hospitalized adolescents diagnosed with depressive disorders.The subjects ranged from 12-18 years in age.Rumi-nation subtypes were assessed using the Ruminative Response Scale,and 12 NSSI behaviors were evaluated using a validated questionnaire.Network analysis was applied to explore symptom-level associations and identify central symptoms.RESULTS The network analysis revealed close connections between rumination subtypes and NSSI behaviors.Brooding was linked to behaviors such as hitting objects and burning.Scratching emerged as the most influential NSSI symptom.Symptomfocused rumination served as a key bridge connecting rumination and NSSI.CONCLUSION Symptom-focused rumination and scratching were identified as potential intervention targets.These findings highlight the psychological significance of specific cognitive-behavioral links in adolescent depression and suggest directions for tailored prevention and treatment.However,the cross-sectional,single-site design limits causal inference and generalizability.Future longitudinal and multi-center studies are needed to confirm causal pathways and verify the generalizability of the findings to broader adolescent populations.
文摘Clinically differentiating bipolarⅡdisorder(BD-Ⅱ)from major depressive disorder(MDD)remains a significant challenge in modern psychiatry.These two conditions share substantial clinical symptomatology,making accurate diagnosis difficult in routine clinical practice.Misdiagnosis may lead to inappropriate treatment strategies,increased psychological and physical burdens,reduced quality of life,and impaired social functioning.Genetic overlap may partially explain the clinical similarities between MDD and BD-Ⅱ,and biomarkers along with neuroimaging techniques are receiving increasing attention as tools to aid in diagnosis.For example,electroencephalography has been shown to effectively distinguish between unipolar depression and bipolar depression;serum levels of glycogen synthase kinase-3 have also been investigated as a potential tool for differentiating between the two disorders.A comprehensive assessment integrating clinical characteristics,genetic basis research,and multimodal evaluations using neuroimaging and biomarkers through a multidisciplinary approach will help enhance clinicians'ability to distinguish between MDD and BD-Ⅱ.By improving diagnostic accuracy,more personalized and effective treatment strategies can be developed,ultimately improving patients'health outcomes and quality of life.
基金funded by Science and Technology Commission of Shanghai Municipality(No.21Y11905400)National Natural ScienceFoundationof China(General Program,No.82371555).
文摘Background Dynamic interpersonal therapy(DIT)is a short-term psychodynamic psychotherapy that has been shown to effectively reduce depressive symptoms in patients with major depressive disorder(MDD).In DIT,the depressive symptoms are formulated as responses to impaired mentalisation.DIT aims to alleviate depressive symptoms by improving mentalising.Aims This study aimed to examine the effect of DIT on improving mentalising and the mediating effect of mentalising in changes in depressive symptoms.Methods Outpatients received either DIT combined with antidepressant medication treatment(DIT group)or antidepressant medication treatment alone(ADM group)for 16 weeks.The Hamilton Depression Rating Scale(HAMD),Patient Health Questionnaire(PHQ)and Reflective Functioning Questionnaire(RFQ)were used.The intention-to-treat principle,mixed linear models,multiple imputation,Pearson's correlation analysis and mediation analysis were conducted.The per-protocol principle was used as sensitivity analysis.Results The DIT group had significantly lower HAMD(least-squares(LS)mean difference=-3.756,p<0.001),PHQ(LS mean difference=-4.188,p<0.001),uncertainty about mental states in the RFQ(RFQ-U,LS mean difference=-2.116,p<0.001)and higher certainty about mental states in the RFQ(RFQ-C,LS mean difference=2.214,p=0.028)scores than the ADM group at post-treatment.The change in RFQ-C was marginally significantly correlated with the change in HAMD(r=-0.218,poretao=0.090),The change in RFQ-U was significantly correlated with the change in HAMD(r=-0.269,poroco-0.024)and the change in PHQ(r=-0.43,Peoretceo l<e0.001).When using RFQ-U as the mediating variable and PHQ as the dependent variable,a significant mediating effect was found(p=0.043,95% confidence interval 0.024 to 1.453).Conclusions The DIT group yielded better outcomes compared with the ADM group in reducing depressive symptoms and improving mentalising.Improvements in mentalising were associated with reductions in depressive symptoms.These findings support that mentalising may contribute to the therapeutic effects of DIT in MDD.
基金Supported by Provincial Key Research Project of Henan Province,No.232102310081.
文摘BACKGROUND Major depressive disorder(MDD)and obesity(OB)are bidirectionally comorbid conditions with common neurobiological underpinnings.However,the neurocognitive mechanisms of their comorbidity remain poorly understood.AIM To examine regional abnormalities in spontaneous brain activity among patients with MDD-OB comorbidity.METHODS This study adopted a regional homogeneity(ReHo)analysis of resting-state functional magnetic resonance imaging.The study included 149 hospital patients divided into four groups:Patients experiencing their first episode of drug-naive MDD with OB,patients with MDD without OB,and age-and sex-matched healthy individuals with and without OB.Whole-brain ReHo analysis was conducted using SPM12 software and RESTplus toolkits,with group comparisons via ANOVA and post-hoc tests.Correlations between ReHo values and behavioral measures were examined.RESULTS ANOVA revealed significant whole-brain ReHo differences among the four groups in four key regions:The left middle temporal gyrus(MTG.L),right cuneus,left precuneus,and left thalamus.Post-hoc analyses confirmed pairwise differences between all groups across these regions(P<0.05).OB was associated with ReHo alterations in the MTG.L,right cuneus,and left thalamus,whereas abnormalities in the precuneus suggested synergistic pathological mechanisms between MDD and OB.Statistically significant correlations were found between the drive and fun-seeking dimensions of the behavioral activation system,as well as behavioral inhibition and the corresponding ReHo values.CONCLUSION Our findings provide novel evidence for the neuroadaptive mechanisms underlying the MDD-OB comorbidity.Further validation could lead to personalized interventions targeting MTG.L hyperactivity and targeting healthy food cues.
基金Supported by Science and Technology Innovation 2030-Major Projects,No.2021ZD0202000National Key Research and Development Program of China,No.2019YFA0706200+2 种基金National Natural Science Foundation of China,No.82371535Science and Technology Innovation Program of Hunan Province,No.2023RC3083Fundamental Research Funds for the Central Universities of Central South University,No.2023ZZTS0838.
文摘BACKGROUND Sensitivity to stress is essential in the onset,clinical symptoms,course,and prognosis of major depressive disorder(MDD).Meanwhile,it was unclear how variously classified but connected stress-sensitivity variables affect MDD.We hypothesize that high-level trait-and state-related stress-sensitivity factors may have different cumulative effects on the clinical symptoms and follow-up outcomes of MDD.AIM To investigate how stress-sensitivity factors added up and affected MDD clinical symptoms and follow-up results.METHODS In this prospective study,281 MDD patients were enrolled from a tertiary care setting.High-level stress-sensitivity factors were classified as trait anxiety,state anxiety,perceived stress,and neuroticism,with a total score in the top quartile of the research cohort.The cumulative effects of stress-sensitivity factors on cognitive dysfunction,disability and functional impairment,suicide risk,and depressive and anxiety symptoms were examined using an analysis of variance with linear trend analysis.Correlations were investigated further using multiple regression analysis.RESULTS Regarding high-level stress-sensitivity factors,53.40%of patients had at least one at baseline,and 29.61%had two or more.Four high-level stress-sensitivity components had significant cumulative impacts on MDD symptoms at baseline(all P<0.001).Perceived stress predicted the greatest effect sizes of state-related factors on depressive symptoms(partialη^(2)=0.153;standardizedβ=0.195;P<0.05).The follow-up outcomes were significantly impacted only by the high-level trait-related components,mainly when it came to depressive symptoms and suicide risk,which were predicted by trait anxiety and neuroticism,respectively(partialη^(2)=0.204 and 0.156;standardizedβ=0.247 and 0.392;P<0.05).CONCLUSION To enhance outcomes of MDD and lower the suicide risk,screening for stress-sensitivity factors and considering multifaceted measures,mainly focusing on trait-related ones,should be addressed clinically.
文摘Background Mental disorders rank among the leading contributors to the global disease burden, with depressive disorders being among the most prevalent.Aims The objective of this study is to examine the prevalence, incidence and years lived with disability (YLDs) associated with depressive disorders, particularly major depressive disorder and dysthymia, in Iran from 1990 to 2021. To achieve this, the research focused on analysing these metrics across various dimensions, including temporal trends, sex differences, age categories and subnational regions.Methods The data used in this study are sourced directly from the Institute for Health Metrics and Evaluation, ensuring that the information is both authoritative and reliable. All-age count estimates and age-standardised rates (per 100 000) were calculated for prevalence, incidence and YLDs. The disease burden indicators were analysed for the period spanning from 1990 to 2021, stratified by sex, age and location. The percentage change between 1990 and 2021 was also documented. The 95% uncertainty interval (UI) was reported for each of the reported estimates.Results The prevalence of depressive disorders in Iran demonstrated a notable upward trend from 1990 to 2021, with the rate of growth being particularly pronounced within the country. The age-standardised prevalence rate per 100 000 individuals for depressive disorders in Iran was 5609 (95% UI 4810 to 6488). By 2021, the number of depression cases in Iran reached 5.2 million, which is approximately 2.37 times the figure reported in 1990. The prevalence of depressive disorders was notably higher among females compared with males. The age-standardised prevalence rate per 100 000 individuals for males was 4184 (95% UI 3545 to 4929). For females, this figure was significantly greater, reaching 7077 (95% UI 6115 to 8172). Out of the total reported cases of depressive disorders in Iran, 3.2 million were observed in females, while males accounted for 2 million cases.Conclusions The findings highlighted the considerable impact of depressive disorders in Iran, both nationally and regionally, while also revealing variations across sex and age groups. Given the shifts in the demographic structure and the growing burden of these disorders, it is essential to prioritise screening initiatives, education programmes and strategies aimed at enhancing mental health awareness and ensuring improved access to mental health services in health policy planning.
文摘Background GW117(N-(2-(6-chloro-7-deuteromethoxynaphthalen-1-yl)ethyl)acetamide)is a dual-acting agent(MT1/MT2 agonist,5-HT_(2C)antagonist)with prior evidence of antidepressant efficacy and favourable safety.Aims To preliminarily evaluate the efficacy and safety of GW117 in major depressive disorder(MDD)and to explore the optimal dosing.Methods A total of 280 eligible patients aged 18-65years with MDD were randomly assigned(1:1:1:1)to8 weeks of double-blind treatment with fixed doses of GW117 tablets(20,40,60 mg/day)or placebo.The primary endpoint was the change from baseline to Week 8 in the total score of the Hamilton Rating Scale for Depression-17item(HAMD-17).Key secondary endpoints included changes in the Montgomery-?sberg Depression Rating Scale(MADRS)total score over the same period.Results In the full analysis set(n=276),GW117 showed numerically greater reductions versus placebo in the HAMD-17 and MADRS total scores,as well as higher response rates at Week 8.However,these differences did not reach statistical significance,potentially due to a high placebo response and other contributing factors.In a post hoc analysis of an optimal subgroup(baseline HAMD-17>24 or insomnia factor>4),GW117 showed efficacy in improving multidimensional symptoms,including insomnia.The 20 mg dose demonstrated a significant3.66-point greater reduction in MADRS(p=0.026)and a23.16%higher response rate(p=0.013)compared with placebo.GW117 was well-tolerated,with no cases of alanine aminotransferase or aspartate aminotransferase exceeding 3×the upper limit of normal and no concerning safety signals reported.Conclusions This exploratory study found that GW117demonstrated encouraging antidepressant efficacy and a favourable safety profile in patients with MDD.Although differences versus placebo did not reach statistical significance in the overall population,GW11720 mg monotherapy showed significant improvements in multidimensional depressive symptoms,including insomnia,in the optimal response subgroup.No hepatotoxicity was reported,supporting its promising therapeutic potential for further clinical development.
基金supported by projects from Shanghai Putuo District Municipal Health Committee(ptkwws202413)Shanghai Municipal Health Commission(202340018)+2 种基金Shanghai Hospital Development Center(Data Sharing and Emulation of Clinical Trials,CCS-DASET:SHDC2024CRI008)Shanghai Changning District Municipal Commission of Health(CNWJXY026)School of Innovation and Entrepreneurship,Tongji University(S202310247388,X2024085 and X2024048).
文摘Background Biomarkers for predicting suicide risk in hospitalised patients with mental disorders have been understudied.Currently,suicide risk assessment tools based on objective indicators are limited in China.Aims To examine the value of various biomarkers in suicide risk prediction and develop a risk assessment model with clinical utility using machine learning.Methods This cohort study analysed patients with major depressive disorder(MDD) who were hospitalised for the first time between January 2016 and March 2023 from four specialised mental health institutions.A total of 139 features,including biomarker measurements,medical orders and psychological scales,were assessed for analysis.Their suicide risk was evaluated by qualified nurses using Nurse s Global Assessment of Suicide Risk within 1 week after admission.Five machine learning models were trained with 10-fold cross-validation across three hospitals and were externally validated in an independent cohort.The primary performance was assessed using the area under the receiver operating characteristic curve(AUROC).The model was interpreted using the SHapley Additive exPlanations(SHAP) analysis.Biomarker importance was evaluated by comparing model performance with and without these biomarkers.Results Of 3143 patients with MDD included in this study,the incidence of high suicide risk within 1 week after first admission was 660(21.0%).Among all models,the Extreme Gradient Boosting can more effectively predict future risks,with an AUROC higher than 0.8(p<0.001).The SHAP values identified the 10 most important features,including five biomarkers.After clustering analysis,electroconvulsive therapy,physical restraint,β2-microglobulin and triiodothyronine were found to have heterogeneous effects on suicide risk.Combining biomarkers with other data from electronic health records significantly improved the performance and clinical utility of machine learning models based on demographics,diagnosis,laboratory tests,medical orders and psychological scales.Conclusions This study demonstrates the potential for a biomarker-based suicide risk assessment for patients with MDD,emphasising the interaction between biomarkers and therapeutic interventions.
文摘Major depressive disorder(MDD),a psychiatric disorder characterized by functional brain deficits,poses considerable diagnostic and treatment challenges,especially in adolescents owing to varying clinical presentations.Biomarkers hold substantial clinical potential in the field of mental health,enabling objective assessments of physiological and pathological states,facilitating early diagnosis,and enhancing clinical decision-making and patient outcomes.Recent breakthroughs combine neuroimaging with machine learning(ML)to distinguish brain activity patterns between MDD patients and healthy controls,paving the way for diagnostic support and personalized treatment.However,the accuracy of the results depends on the selection of neuroimaging features and algorithms.Ensuring privacy protection,ML model accuracy,and fostering trust are essential steps prior to clinical implementation.Future research should prioritize the establishment of comprehensive legal frameworks and regulatory mechanisms for using ML in MDD diagnosis while safeguarding patient privacy and rights.By doing so,we can advance accuracy and personalized care for MDD.
基金supported by the National Key Research and Development Program of China(No.2022YFE0201000)National Natural Science Foundation of China(Nos.82472092,82174002,81874374 and 81673625)+2 种基金a grant from the Research Center for Brain Cognition and Human Development,Guangdong,China(No.2024B0303390003)Key Realm R&D Program of Guangzhou(No.202206010109)Taizhou Science and Technology Support Program(Social Development)project(No.TS2016-12).
文摘Background Yueju Pill,a classic traditional Chinese medicine,shows antidepressant effects rapidly.However,biomarkers that can predict its treatment outcomes in major depressive disorder(MDD)are still lacking.Multimodal magnetic resonance imaging(MRI)offers a promising avenue to identify such biomarkers.Aims This pilot study aimed to explore whether therapeutic responses to Yueju Pill could be predicted by MRI-derived brain networks and to identify drug-specific biomarkers in comparison to escitalopram,a mainstream antidepressant.Methods We collected multimodal MRI data and blood samples from 28 outpatients with MDD from the Fourth People's Hospital of Taizhou,who were randomly divided into two groups to receive either Yueju Pill(23 g/time/day)or escitalopram(10 mg,two times a day)for 4 days.Morphological and functional brain networks were constructed and used to predict individual changes in symptoms quantified by the 24-item Hamilton Depression Scale(HAMD-24)scores and serum brain-derived neurotrophic factor(BDNF)levels.Results After the treatment,both groups exhibited significant reductions in the HAMD-24 scores,while only the Yueju Pill group showed significant increases in the BDNF levels.Gyrification Index-based morphological networks predicted change rates of the HAMD-24 scores in both groups,but sulcus depth-based and cortical thickness-based morphological networks predicted change rates of the HAMD-24 scores and BDNF levels,respectively,only in the Yueju Pill group.Subnetwork analyses revealed that the visual network independently predicted the changes in both the HAMD-24 scores(sulcus depth-based networks)and BDNF levels(cortical thickness-based networks)following Yueju Pill treatment.Conclusions Morphological but not functional brain networks can predict symptom improvement and BDNF changes of patients with MDD after Yueju Pill treatment.Sulcus depth-based and cortical thickness-based morphological brain networks,particularly their visual subnetworks,might serve as Yueju Pill-specific biomarkers for predicting the therapeutic responses.These findings have the potential to guide personalised therapy for patients with MDD early in the therapeutic process.
基金supported by the National Natural Science Foundation of China(82071500,82271540,32370724,82401759,81871055,32070679)Shanghai Clinical Research Center for Mental Health(19MC1911100)+11 种基金Shanghai Key Laboratory of Psychotic Disorders(13dz2260500)Shanghai Municipal Administrator of Traditional Chinese Medicine(ZY-(2021-2023)-0207-01)Shanghai Municipal Health Commission Collaborative Innovation Group(2024CXJQ03)Shanghai Science and Technology Innovation Action Program(24JS2840400,24ZR1439900,21Y11921100)Shanghai Municipal Science and Technology Major Project,the National Key R&D Program of China(2023YFA0913804,2024YFA0916603,2022FYC2503300)the Program of Shanghai Academic/Technology Research Leader(21XD1423300)Shanghai Pujiang Program(21PJD063)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)Shanghai Municipal Commission of Education(2024AIZD016)the National Key R&D Program of China(2019YFA0905400,2017YFC0908105,2021YFC2702100)National Program for Support of Top-Notch Young Professionals,Taishan Scholar Program of Shandong Province(tstp20240526)the Natural Science Foundation of Shandong Province(ZR2019YQ14,YDZX2021009,2021ZDSYS06).
文摘Background Numerous studies have consistently demonstrated that a considerable proportion of patients with major depressive disorder (MDD) frequently exhibit pronounced dyslipidaemia. However, the causal dynamics between MDD and dyslipidaemia remain elusive.Aims To comprehensively disentangle the genetic causality between MDD and various phenotypes of blood lipids, thereby facilitating the advancement of management strategies for these conditions.Methods We conducted a two-sample univariable Mendelian randomisation (MR) analysis using different models, including the inverse variance weighted (IVW) method and causal analysis using the summary effect (CAUSE) estimates, as well as a multivariable MR analysis. This analysis used summary statistics from genome-wide association studies (GWAS) of MDD and five lipid traits: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, total cholesterol and triglycerides (TG), encompassing 5 237 893 individuals of European and East Asian ancestries. For MDD, a total of 598 701 individuals were included, with 500 199 individuals of European ancestry (Ncase=170 756, Ncontrol=329 443) and 98 502 of East Asian ancestry (Ncase=12 588, Ncontrol=85 914). Lipid data were collected from 4 639 192 individuals through the Global Lipids Genetics Consortium (European, N=4 096 085;East Asian, N=543 107). Next, we used the two-step MR to explore the mediating factors between MDD and TG, and the risk factors affecting TG through MDD. Finally, we conducted a GWAS meta-analysis and enrichment analysis.Results In univariable MR, we observed a negative causal effect of low-density lipoprotein on MDD in both European populations (IVW: odds ratio (OR): 0.972, 95% confidence interval (CI) 0.947 to 0.998, p=0.037) and East Asian populations (IVW: OR: 0.928, 95% CI 0.864 to 0.997, p=0.042). Additionally, we identified a bidirectional causal relationship between TG and MDD, with TG having a causal effect on MDD (IVW: OR: 1.052, 95% CI 1.020 to 1.085, p=0.001) and MDD having a causal effect on TG (IVW: OR: 1.075, 95% CI 1.047 to 1.104, p<0.001). Multivariable MR analysis further supported the role of TG in MDD (OR: 1.205, 95% CI 1.034 to 1.405, p=0.017). CAUSE estimates indicated that the causal model of MDD on TG provided a better fit than the sharing model (p=0.003), while the association of TG on MDD was more likely due to horizontal correlated pleiotropy than causality. Mediation analyses revealed that waist-hip ratio (WHR) mediated 69% of the total causal effect of MDD on TG, while other identified risk factors exhibited lower mediating proportions either mediated through MDD (≤17%) or originating from MDD (≤29%). The GWAS meta-analysis highlighted potential pathways related to lipid processes and nucleosome assembling, with significant cell types identified in brain regions and liver tissues.Conclusions The findings indicate that genetic proxies of MDD are associated with elevated levels of TG, with WHR serving as a clinical indicator of the association. This suggests that interventions targeting WHR may be effective in reducing TG levels in patients with MDD.
文摘Background Metabolic dysregulation has been implicated in major depressive disorder(MDD).Aims We aimed to explore the potential role of plasma metabolites in MDD.Methods We conducted Mendelian randomisation(MR)analysis to evaluate the causal effects of 871 circulating metabolites on MDD,using the Genome-Wide Association Studies datasets of MDD(N=1035760)and metabolites(N=8299).Bayesian colocalisation and druggability analyses were employed to identify genetic variants contributing to both MDD and levels of metabolites in plasma and to pinpoint metabolites with therapeutic potential,respectively.Results MR analysis identified 11 metabolites associated with MDD(false discovery rate<0.05).Eight metabolites,including arachidonate(20:4n6)(odds ratio(OR):0.97),1-arachidonoyl-GPC(20:4n6)(OR:0.98),1-(1-enylpalmitoyl)-2-palmitoleoyl-GPC(P-16:0/16:1)(OR:0.97),succinoyltaurine(OR:0.98),3-methoxycatechol sulphate(1)(OR:0.98)and 11β-hydroxyandrosterone glucuronide(OR:0.97),showed protective effects against MDD.Three metabolites were associated with increased risk,namely,butyrylglycine(OR:1.03),3-carboxy-4-methyl-5-propyl-2-furanpropanoate(OR:1.02)and 1-(1-enyl-stearoyl)-2-oleoyl-GPE(P-18:0/18:1)(OR:1.02).Colocalisation analysis supported shared genetic signals between five lipid metabolites and MDD,particularly at loci harbouring FADS and ATP9A.Notably,a majority of metabolites associated with MDD are being explored as therapeutic targets for various psychiatric disorders.Conclusions Genetically predicted levels of certain circulating metabolites make a causal contribution to MDD.Further investigation of their roles may provide novel pathophysiological insights and give clues for targeted therapies.
基金supported by the National Natural Science Foundation of China(No.82371530,82171529)the Capital Health Development Special Research Project(2022-1-4111)the National Key Technology R and D Program(No.2015BAI13B01).
文摘Background The patient-reported Dimensional Anhedonia Rating Scale(DARS)has been adapted into Chinese,so there is a need to evaluate its measurement properties in a Chinese population.Aims To evaluate the reliability and validity of the DARS among Chinese individuals with major depressive disorder(MDD)and its treatment sensitivity in a prospective clinical study.Methods Data were from a multicentre,prospective clinical study(NCT03294525),which recruited both patients with MDD,who were followed for 8 weeks,and healthy controls(HCs),assessed at baseline only.The analysis included confirmatory factor analysis,validity and sensitivity to change.Results Patients’mean(standard deviation(SD))age was 34.8(11.0)years,with 68.7%being female.75.2%of patients with MDD had melancholic features,followed by 63.8%with anxious distress.Patients had experienced MDD for a mean(SD)of 9.2(18)months.DARS scores covered the full range of severity with no major floor or ceiling effects.Confirmatory factor analysis showed adequate fit statistics(comparative fit index 0.976,goodness-of-fit index 0.935 and root mean square error of approximation 0.055).Convergent validity with anhedonia-related measures was confirmed.While the correlation between the DARS and the Hamilton Depression Rating Scale was not strong(r=0.31,baseline),the DARS was found to differentiate between levels of depression.Greater improvements in DARS scores were seen with the Hamilton Rating Scale for Depression responder group(effect size 1.16)compared with the non-responder group(effect size 0.46).Conclusions This study comprehensively evaluated the measurement properties of the DARS using a Chinese population with MDD.Overall,the Chinese version of DARS demonstrates good psychometric properties and has been found to be responsive to change during antidepressant treatment.The DARS is a suitable scale for assessing patient-reported anhedonia in future clinical trials.
基金Supported by National Natural Science Foundation of China,No.82373660 and No.81761128030Sanming Project of Medicine in Shenzhen Nanshan,No.11the China Scholarship Council。
文摘BACKGROUND Childhood maltreatment has a potentially lasting influence on subthreshold depressive symptoms(SDS)and major depressive disorder(MDD).This study aimed to explore the association of childhood maltreatment with MDD and SDS,focusing on the differences between young and middle-aged adults.AIMTo examine the associations among childhood maltreatment, SDS, and MDD in young and middle-aged adults.METHODSA total of 3209 adults were recruited from 34 primary healthcare settings. The Childhood Trauma Questionnaire-28item Short Form was used to assess childhood maltreatment. The Patient Health Questionnaire-9 was used toassess SDS and the Mini-International Neuropsychiatric Interview depression module was used to assess MDD.RESULTSChildhood maltreatment was significantly associated with higher odds of developing SDS and MDD than in thenon-depressed control group (P < 0.05). Childhood maltreatment significantly increased the risk of developing SDSin young adults but was not significantly associated with SDS in middle-aged adults (P = 0.055). Conversely,childhood maltreatment was significantly associated with MDD in both young (P < 0.001) and middle-aged adults(P < 0.05). In young adults, various types of childhood maltreatment were associated with MDD;however, onlyemotional abuse and neglect were significantly associated with MDD in middle-aged adults.CONCLUSIONOur study revealed a strong association among childhood maltreatment, SDS, and MDD across age groups,highlighting the impact of emotional abuse and need for trauma-informed depression care.
基金supported by the National Natural Science Foundation of China,No.81971269 (to DP)the Science and Technology Commission of Shanghai,No.YDZX20213100001003 (to DP)。
文摘In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.
文摘BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affecting work and interpersonal communication,increasing the risk of recurrence,and adding to the burden on families.Studying the influencing factors of their social function is of great significance.AIM To explore the social function score and its influencing factors in patients with residual depressive symptoms.METHODS This observational study surveyed patients with residual depressive symptoms(case group)and healthy patients undergoing physical examinations(control group).Participants were admitted between January 2022 and December 2023.Social functioning was assessed using the Sheehan Disability Scale(SDS),and scores were compared between groups.Factors influencing SDS scores in patients with residual depressive symptoms were analyzed by applying multiple linear regression while using the receiver operating characteristic curve,and these RESULTS The SDS scores of the 158 patients with depressive symptoms were 11.48±3.26.Compared with the control group,the SDS scores and all items in the case group were higher.SDS scores were higher in patients with relapse,discon-tinuous medication,drug therapy alone,severe somatic symptoms,obvious residual symptoms,and anxiety scores≥8.Disease history,medication compliance,therapy method,and residual symptoms correlated positively with SDS scores(r=0.354,0.414,0.602,and 0.456,respectively).Independent influencing factors included disease history,medication compliance,therapy method,somatic symptoms,residual symptoms,and anxiety scores(P<0.05).The areas under the curve for predicting social functional impairment using these factors were 0.713,0.559,0.684,0.729,0.668,and 0.628,respectively,with sensitivities of 79.2%,61.8%,76.8%,81.7%,63.6%,and 65.5%and specificities of 83.3%,87.5%,82.6%,83.3%,86.7%,and 92.1%,respectively.CONCLUSION The social function scores of patients with residual symptoms of depression are high.They are affected by disease history,medication compliance,therapy method,degree of somatic symptoms,residual symptoms,and anxiety.
基金funded by the Construction Project of the"Flagship"Department of Chinese and Western Medicine Coordination(LiuL/2024-221)the 2024 Medical Service and Security Capacity Improvement Project(National Clinical Key Specialty Construction)(LiuL/Huwei Medical/2024-65)+5 种基金the Shanghai Traditional Chinese Medicine Standardization Project(LiuL/No.2023JSP03)the Shanghai Key Discipline Construction Project of Traditional Chinese Medicine(Clinical)(LiuL/2024-No.3)the Shanghai Technical Standardization Management and Promotion Project(LiuL/No.SHDC22023212)the Shanghai Municipal Health Commission Traditional Chinese Medicine Research Project(2022)(LiuL/No.2022Cx004)Clinical research project of Shanghai Health Commission-Youth Project(LW/No.20214Y0056)Shanghai Institute of Traditional Chinese Medicine for Mental Health(LW/No.SZB2023201).
文摘INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depression leads to social and occupational impairment,diminished quality of life and an elevated risk of death by suicide.
基金Supported by Wuxi Taihu Talent Project,No.WXTTP 2021the General Scientific Research Program of Wuxi Municipal Health Commission,No.M202447.
文摘BACKGROUND Research has consistently demonstrated that patients with major depressive disorder(MDD)exhibit attentional switching dysfunction,and the dual-task paradigm has emerged as a valuable tool for probing cognitive deficits.However,the neuroelectrophysiological mechanism underlying this deficit has not been clarified.AIM To investigate the event-related potential(ERP)characteristics of attentional switching dysfunction and further explore the neuroelectrophysiological mechanism of the cognitive processing deficits underlying attentional switching dysfunction in MDD.METHODS The participants included 29 MDD patients and 29 healthy controls(HCs).The ERPs of the participants were measured while they performed the dual-task para digm.The behavioral and ERP N100,P200,P300,and late positive potential(LPP)data were analyzed.RESULTS This study revealed greater accuracy in HCs and slower reaction times(RTs)in MDD patients.Angry facial pictures led to lower accuracy.The results also revealed shorter RTs for happy facial pictures and the longest RTs for the 500-ms stimulus onset asynchrony.With respect to ERP characteristics,happy facial pictures and neutral facial pictures evoked higher amplitudes.The N100,P200,P300,and LPP amplitudes at Pz were the highest.MDD patients had lower P200 mean amplitudes and LPP amplitudes than HCs did.CONCLUSION In conclusion,MDD patients exhibited abnormal ERP characteristics evoked by the dual-task paradigm,which could be the neural correlates of the known abnormalities in attentional switching in patients with MDD.These results provide valuable insights into the understanding of the neural mechanisms of attentional switching function and may guide targeted interventions in patients with MDD.
基金Supported by Hubei Provincial Department of Science and Technology Natural Fund,No.2024AFC056the Open Fund of the Mental Health Research Institute at Three Gorges University,No.YCXL-23-11.
文摘BACKGROUND Major depressive disorder(MDD)with comorbid anxiety is an intricate psychiatric condition,but limited research is available on the degree centrality(DC)between anxious MDD and nonanxious MDD patients.AIM To examine changes in DC values and their use as neuroimaging biomarkers in anxious and non-anxious MDD patients.METHODS We examined 23 anxious MDD patients,30 nonanxious MDD patients,and 28 healthy controls(HCs)using the DC for data analysis.RESULTS Compared with HCs,the anxious MDD group reported markedly reduced DC values in the right fusiform gyrus(FFG)and inferior occipital gyrus,whereas elevated DC values in the left middle frontal gyrus and left inferior parietal angular gyrus.The nonanxious MDD group exhibited surged DC values in the bilateral cerebellum IX,right precuneus,and opercular part of the inferior frontal gyrus.Unlike the nonanxious MDD group,the anxious MDD group exhibited declined DC values in the right FFG and bilateral calcarine(CAL).Besides,declined DC values in the right FFG and bilateral CAL negatively correlated with anxiety scores in the MDD group.CONCLUSION This study shows that abnormal DC patterns in MDD,especially in the left CAL,can distinguish MDD from its anxiety subtype,indicating a potential neuroimaging biomarker.
