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
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 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 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
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 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
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 Major depressive disorder(MDD),characterised by persistent anhedonia and elevated suicide risk,represents a global mental health challenge.Recent studies suggest a link between gut-brain axis dysfunction an...Background Major depressive disorder(MDD),characterised by persistent anhedonia and elevated suicide risk,represents a global mental health challenge.Recent studies suggest a link between gut-brain axis dysfunction and depression.The natural compound paeoniflorin demonstrates clinically relevant antidepressant effects,yet its underlying neurobiological mechanisms remain elusive.Aims This study aims to examine how paeoniflorin alleviates depression-like behaviours in rats subjected to chronic unpredictable mild stress(CUMS)by modulating the function of gut-brain axis,and explore the connections between gut microbiota,metabolites and MDD.Methods Depression-like behaviours in rats were induced by CUMS,and the antidepressant effect of paeoniflorin was assessed using behavioural tests.The composition and function of the intestinal microbiota were analysed using 16S rRNA sequencing,and metabolomic analysis was performed on serum,hippocampus,jejunum and faecal samples.Enzyme-linked immunosorbent assay and hematoxylin and eosin staining were used to detect the levels of inflammatory factors and cortisol,as well as the infiltration of inflammatory cells in the jejunum of rats after cohousing.Long-term potentiation assays and Golgi staining were used to detect dendritic spine density and synaptic plasticity,respectively.Results Paeoniflorin significantly alleviated depression-like behaviours and cognitive deficits in CUMS rats.16S rRNA sequencing revealed that paeoniflorin improved the abundance and diversity of the gut microbiota in CUMS rats.Enrichment of differential metabolites in the brain,intestine,faeces and serum revealed a primary accumulation in the amino acid metabolism pathway.We further observed a correlation between the relative abundance of microbial communities and metabolites.Cohousing experiments verified that microbial metabolites of paeoniflorin can reduce neuroinflammation and improve synaptic plasticity.Conclusions Disruptions in gut microbiota and its metabolites impair gut-brain interactions.Paeoniflorin’s neuroprotective and antidepressant effects are mediated through the modulation of the function of the gut-brain axis.展开更多
There is growing evidence that lipid metabolism instability in depressive disorder may be a core early pathological event associated with numerous pathogenesis hypotheses.However,spatial distributions and quantitative...There is growing evidence that lipid metabolism instability in depressive disorder may be a core early pathological event associated with numerous pathogenesis hypotheses.However,spatial distributions and quantitative changes of lipids in specific brain regions associated with depressive disorder are far from elucidated.In the present study,lipid profiling characteristics of whole brain sections are systematically determined by using matrix-assisted laser desorption ionization-mass spectrometry imaging(MALDI-MSI)-combined with histomorphological analysis in rats with depressive-like behavior induced by multiple early life stress(mELS)and unstressed control.Lipid dyshomeostasis and different degrees of metabolic disturbance occur in the eight paired representative brain sections from micro-region and molecular level.More specifically,17 lipid molecules show the severe dyshomeostasis between intergroup(control and depressed rats)or intra-group(multiple emotion-regulation-related brain regions).Quite specially,phosphatidylcholine(PC)(39:6)expression in section 7 is significantly upregulated only in the amygdala of depressed rat relative to control rat,by contrast,up-regulated phosphatidylglycerol(PG)(34:2)in section 2 emerges in the medial prefrontal cortex,insular cortex,and nucleus accumbens simultaneously.Linking spatial distribution to quantitative variation of lipids from the whole brain sections contributes the uncovering of new insights in causal mechanism of lipid dyshomeostasis in depression investigation and related targeting interventions.展开更多
BACKGROUND Depression is a significant risk factor for diabetes,particularly type 2 diabetes.However,depressive symptoms differ from clinical depression.Previous research has not fully considered the relationship betw...BACKGROUND Depression is a significant risk factor for diabetes,particularly type 2 diabetes.However,depressive symptoms differ from clinical depression.Previous research has not fully considered the relationship between the trajectory of depressive symptoms and the risk of developing diabetes over time.AIM To investigate the association between depressive symptoms,their trajectories,and the risk of developing diabetes in two prospective cohort studies.METHODS In the first phase we analyzed the association between depressive symptoms and the risk of developing diabetes separately using the Health and Retirement Study(HRS).Depressive symptom trajectories were assessed by examining changes in depressive symptoms at baseline and again 8 years later.We then identified specific depressive symptom trajectories that increased the risk of diabetes in the second phase.Finally,we confirmed the association between depressive symptoms and their trajectories with diabetes risk using the English Longitudinal Study of Ageing(ELSA)as a validation study.Depressive symptom trajectories were categorized into five states based on changes in the modified 8-item Center for Epidemiological Studies-Depression scores:Persistently high;increasing;fluctuating;decreasing;and persistently low.Diabetes mellitus was defined as self-reported,physician-diagnosed diabetes.Cox proportional hazards models were used to assess hazard ratios(HR)and 95%confidence intervals(CI),adjusting for potential confounders.RESULTS In the first phase a total of 27658 participants were included(HRS:18633,ELSA:9025),among whom 6582 had depressive symptoms(HRS:4547,ELSA:2035),6407 had somatic depressive symptoms(HRS:4414,ELSA:1993),and 26415 had cognitive-affective depressive symptoms(HRS:17755,ELSA:8660).We found that overall depressive symptoms(HRS:HR=1.14,95%CI:1.07-1.22;ELSA:HR=1.18,95%CI:1.03-1.34)and somatic depressive symptoms(HRS:HR=1.14,95%CI:1.07-1.22;ELSA:HR=1.25,95%CI:1.10-1.42)increased the risk of diabetes,while cognitive depressive symptoms were not associated with diabetes risk.Over an 8-year follow-up we identified 19729 trajectories of overall,somatic,and cognitive-affective depressive symptoms(HRS:13918,ELSA:5811).In the second phase we found that persistently high(HRS:HR=1.22,95%CI:1.06-1.40,ELSA:HR=1.54,95%CI:1.16-2.05 in total and HRS:HR=1.24,95%CI:1.07-1.43,ELSA:HR=1.79,95%CI:1.36-2.35 in somatic)and fluctuating(HRS:HR=1.09,95%CI:1.01-1.17,ELSA:HR=1.33,95%CI:1.14-1.55 in total and HRS:HR=1.10,95%CI:1.02-1.18,ELSA:HR=1.31,95%CI:1.13-1.53 in somatic)trajectories of overall and somatic depressive symptoms increased the risk of diabetes,while increasing trajectories may also raise diabetes risk.However,decreasing trajectories were not associated with diabetes risk.Cognitive-affective depressive symptoms showed no association with diabetes risk regardless of trajectory changes.Sensitivity analyses confirmed the reliability of the findings.CONCLUSION Persistently high and fluctuating trajectories of overall and somatic depressive symptoms increased the risk of diabetes,while decreasing trajectories were not associated with diabetes risk.In contrast trajectories of cognitiveaffective depressive symptoms show no relationship with diabetes risk.Focusing on depressive symptom trajectories,particularly those of somatic depressive symptoms,represented a viable strategy for future diabetes prevention.展开更多
Breast cancer is the most common cancer in women worldwide.A high percentage of these patients may have depressive symptoms and an early detection is crucial as part of a comprehensive management of the disease.Mao et...Breast cancer is the most common cancer in women worldwide.A high percentage of these patients may have depressive symptoms and an early detection is crucial as part of a comprehensive management of the disease.Mao et al recently conducted a study constructing a depression risk predictive model in young and middle-aged breast cancer patients.Four questionnaires(a general one,Patient Health Questionnaire-9,Perceived Social Support From Family Scale and International Physical Activity Questionnaire)and the Visual Analogue Scale were used to examine the correlation between different variables and depressive symptoms.The constructed predictive model showed strong predictive capability with an area under the receiver operating characteristic curve of 0.852 and high sensitivity and specificity values.However,the screening depression tools and questionnaires to assess social support or physical activity are not originally designed for oncological patients and further investigation to corroborate their applicability in this context is relevant.The cross-sectional design of the study prevents establishing clear causal relationships between the identified risk factors and depression.Besides,the study includes only a sample of Chinese patients and the applicability in a different sociocultural context is uncertain.Further investigation is crucial to corroborate the results in larger samples and different contexts.展开更多
BACKGROUND Cognitive impairment is one of the common clinical manifestations of depression,causing negative distress to patients.Elevated homocysteine(Hcy)concentrations and gut microbiome dysfunction may be observed ...BACKGROUND Cognitive impairment is one of the common clinical manifestations of depression,causing negative distress to patients.Elevated homocysteine(Hcy)concentrations and gut microbiome dysfunction may be observed in patients with depression.AIM To investigate the relationship between Hcy,microbiome,and cognition in depressive patients.METHODS We recruited 67 patients with major depressive disorder(MDD)(MDD group)and 94 healthy controls(HCs)individuals(HCs group).Serum Hcy levels were determined using the enzyme circulation method.16s rRNA sequencing was used to classify and identify the fecal bacteria.17 Hamilton depression rating scale and MATRICS consensus cognitive battery were used to evaluate mood states and cognition in patients with MDD. Correlation analysis was performed to explore the correlation between fecal flora,Hcy, and depressive cognitive function.RESULTSElevated serum levels of Hcy were seen in patients with MDD compared to healthy individuals. Patients withMDD indicated significant decreases in cognitive scores (P < 0.001) in six modules: Speed of processing, workingmemory, visual learning, reasoning and problem-solving, social cognition, and total scores. Hcy levels showed anegative correlation with processing speed, social cognition, and total MDD scores (P < 0.05). Hcy was alsosignificantly negatively correlated with Alistipes, Ruminococcae, Tenericides, and Porphyromonas (P < 0.05).CONCLUSIONOur results highlight that Hcy was correlated with cognition and gut microbiome in MDD. This interaction may berelated to the physiological and pathological mechanisms underlying cognitive deficits in depression.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 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.
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.
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 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.
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.
基金supported by the National Natural Science Foundation of China(No 82305144)the Jiangsu Provincial Natural Science Foundation Project for Universities(No 23KJB360004)the National Natural Science Foundation Supporting Project of Nanjing University of Chinese Medicine(No XPT82305144).
文摘Background Major depressive disorder(MDD),characterised by persistent anhedonia and elevated suicide risk,represents a global mental health challenge.Recent studies suggest a link between gut-brain axis dysfunction and depression.The natural compound paeoniflorin demonstrates clinically relevant antidepressant effects,yet its underlying neurobiological mechanisms remain elusive.Aims This study aims to examine how paeoniflorin alleviates depression-like behaviours in rats subjected to chronic unpredictable mild stress(CUMS)by modulating the function of gut-brain axis,and explore the connections between gut microbiota,metabolites and MDD.Methods Depression-like behaviours in rats were induced by CUMS,and the antidepressant effect of paeoniflorin was assessed using behavioural tests.The composition and function of the intestinal microbiota were analysed using 16S rRNA sequencing,and metabolomic analysis was performed on serum,hippocampus,jejunum and faecal samples.Enzyme-linked immunosorbent assay and hematoxylin and eosin staining were used to detect the levels of inflammatory factors and cortisol,as well as the infiltration of inflammatory cells in the jejunum of rats after cohousing.Long-term potentiation assays and Golgi staining were used to detect dendritic spine density and synaptic plasticity,respectively.Results Paeoniflorin significantly alleviated depression-like behaviours and cognitive deficits in CUMS rats.16S rRNA sequencing revealed that paeoniflorin improved the abundance and diversity of the gut microbiota in CUMS rats.Enrichment of differential metabolites in the brain,intestine,faeces and serum revealed a primary accumulation in the amino acid metabolism pathway.We further observed a correlation between the relative abundance of microbial communities and metabolites.Cohousing experiments verified that microbial metabolites of paeoniflorin can reduce neuroinflammation and improve synaptic plasticity.Conclusions Disruptions in gut microbiota and its metabolites impair gut-brain interactions.Paeoniflorin’s neuroprotective and antidepressant effects are mediated through the modulation of the function of the gut-brain axis.
基金supported by the China Science and Technology Innovation 2030-Major Project(Nos.2022ZD0211701,2021ZD0200700)the National Natural Science Foundation of China(Nos.82130042,81830040,22176195,82127801)+3 种基金Shenzhen Science and Technology Serial Funds(Nos.GJHZ20210705141400002,KCXFZ20211020164543006,JCYJ20220818101615033,ZDSYS20220606100606014,KQTD 20221101093608028)the National Key R&D Program of China(No.2022YFF0705003)Guangdong Province Zhu Jiang Talents Plan(No.2021QN02Y028)the Guangdong Science and Technology Department(No.2021B1212030004)。
文摘There is growing evidence that lipid metabolism instability in depressive disorder may be a core early pathological event associated with numerous pathogenesis hypotheses.However,spatial distributions and quantitative changes of lipids in specific brain regions associated with depressive disorder are far from elucidated.In the present study,lipid profiling characteristics of whole brain sections are systematically determined by using matrix-assisted laser desorption ionization-mass spectrometry imaging(MALDI-MSI)-combined with histomorphological analysis in rats with depressive-like behavior induced by multiple early life stress(mELS)and unstressed control.Lipid dyshomeostasis and different degrees of metabolic disturbance occur in the eight paired representative brain sections from micro-region and molecular level.More specifically,17 lipid molecules show the severe dyshomeostasis between intergroup(control and depressed rats)or intra-group(multiple emotion-regulation-related brain regions).Quite specially,phosphatidylcholine(PC)(39:6)expression in section 7 is significantly upregulated only in the amygdala of depressed rat relative to control rat,by contrast,up-regulated phosphatidylglycerol(PG)(34:2)in section 2 emerges in the medial prefrontal cortex,insular cortex,and nucleus accumbens simultaneously.Linking spatial distribution to quantitative variation of lipids from the whole brain sections contributes the uncovering of new insights in causal mechanism of lipid dyshomeostasis in depression investigation and related targeting interventions.
文摘BACKGROUND Depression is a significant risk factor for diabetes,particularly type 2 diabetes.However,depressive symptoms differ from clinical depression.Previous research has not fully considered the relationship between the trajectory of depressive symptoms and the risk of developing diabetes over time.AIM To investigate the association between depressive symptoms,their trajectories,and the risk of developing diabetes in two prospective cohort studies.METHODS In the first phase we analyzed the association between depressive symptoms and the risk of developing diabetes separately using the Health and Retirement Study(HRS).Depressive symptom trajectories were assessed by examining changes in depressive symptoms at baseline and again 8 years later.We then identified specific depressive symptom trajectories that increased the risk of diabetes in the second phase.Finally,we confirmed the association between depressive symptoms and their trajectories with diabetes risk using the English Longitudinal Study of Ageing(ELSA)as a validation study.Depressive symptom trajectories were categorized into five states based on changes in the modified 8-item Center for Epidemiological Studies-Depression scores:Persistently high;increasing;fluctuating;decreasing;and persistently low.Diabetes mellitus was defined as self-reported,physician-diagnosed diabetes.Cox proportional hazards models were used to assess hazard ratios(HR)and 95%confidence intervals(CI),adjusting for potential confounders.RESULTS In the first phase a total of 27658 participants were included(HRS:18633,ELSA:9025),among whom 6582 had depressive symptoms(HRS:4547,ELSA:2035),6407 had somatic depressive symptoms(HRS:4414,ELSA:1993),and 26415 had cognitive-affective depressive symptoms(HRS:17755,ELSA:8660).We found that overall depressive symptoms(HRS:HR=1.14,95%CI:1.07-1.22;ELSA:HR=1.18,95%CI:1.03-1.34)and somatic depressive symptoms(HRS:HR=1.14,95%CI:1.07-1.22;ELSA:HR=1.25,95%CI:1.10-1.42)increased the risk of diabetes,while cognitive depressive symptoms were not associated with diabetes risk.Over an 8-year follow-up we identified 19729 trajectories of overall,somatic,and cognitive-affective depressive symptoms(HRS:13918,ELSA:5811).In the second phase we found that persistently high(HRS:HR=1.22,95%CI:1.06-1.40,ELSA:HR=1.54,95%CI:1.16-2.05 in total and HRS:HR=1.24,95%CI:1.07-1.43,ELSA:HR=1.79,95%CI:1.36-2.35 in somatic)and fluctuating(HRS:HR=1.09,95%CI:1.01-1.17,ELSA:HR=1.33,95%CI:1.14-1.55 in total and HRS:HR=1.10,95%CI:1.02-1.18,ELSA:HR=1.31,95%CI:1.13-1.53 in somatic)trajectories of overall and somatic depressive symptoms increased the risk of diabetes,while increasing trajectories may also raise diabetes risk.However,decreasing trajectories were not associated with diabetes risk.Cognitive-affective depressive symptoms showed no association with diabetes risk regardless of trajectory changes.Sensitivity analyses confirmed the reliability of the findings.CONCLUSION Persistently high and fluctuating trajectories of overall and somatic depressive symptoms increased the risk of diabetes,while decreasing trajectories were not associated with diabetes risk.In contrast trajectories of cognitiveaffective depressive symptoms show no relationship with diabetes risk.Focusing on depressive symptom trajectories,particularly those of somatic depressive symptoms,represented a viable strategy for future diabetes prevention.
文摘Breast cancer is the most common cancer in women worldwide.A high percentage of these patients may have depressive symptoms and an early detection is crucial as part of a comprehensive management of the disease.Mao et al recently conducted a study constructing a depression risk predictive model in young and middle-aged breast cancer patients.Four questionnaires(a general one,Patient Health Questionnaire-9,Perceived Social Support From Family Scale and International Physical Activity Questionnaire)and the Visual Analogue Scale were used to examine the correlation between different variables and depressive symptoms.The constructed predictive model showed strong predictive capability with an area under the receiver operating characteristic curve of 0.852 and high sensitivity and specificity values.However,the screening depression tools and questionnaires to assess social support or physical activity are not originally designed for oncological patients and further investigation to corroborate their applicability in this context is relevant.The cross-sectional design of the study prevents establishing clear causal relationships between the identified risk factors and depression.Besides,the study includes only a sample of Chinese patients and the applicability in a different sociocultural context is uncertain.Further investigation is crucial to corroborate the results in larger samples and different contexts.
基金Supported by the Wuxi Municipal Health Commission Youth Fund Project,No.Q202268Wuxi Scientific and technological breakthrough of“Light of the Taihu Lake”(Basic Research),No.K20221039+4 种基金Jiangsu Shuangchuang Doctoral Program,No.JSSCBS20221991Beijing Municipal Administration of Hospital Incubating Program,No.PX2023070 and No.PX2024072Capital’s Funds for Health Improvement and Research,No.SF2024-4-2134Beijing Hospitals Authority Youth Program,No.QML20232003the Top Talent Support Program for young and middle-aged people of Wuxi Health Committee,No.HB2023089.
文摘BACKGROUND Cognitive impairment is one of the common clinical manifestations of depression,causing negative distress to patients.Elevated homocysteine(Hcy)concentrations and gut microbiome dysfunction may be observed in patients with depression.AIM To investigate the relationship between Hcy,microbiome,and cognition in depressive patients.METHODS We recruited 67 patients with major depressive disorder(MDD)(MDD group)and 94 healthy controls(HCs)individuals(HCs group).Serum Hcy levels were determined using the enzyme circulation method.16s rRNA sequencing was used to classify and identify the fecal bacteria.17 Hamilton depression rating scale and MATRICS consensus cognitive battery were used to evaluate mood states and cognition in patients with MDD. Correlation analysis was performed to explore the correlation between fecal flora,Hcy, and depressive cognitive function.RESULTSElevated serum levels of Hcy were seen in patients with MDD compared to healthy individuals. Patients withMDD indicated significant decreases in cognitive scores (P < 0.001) in six modules: Speed of processing, workingmemory, visual learning, reasoning and problem-solving, social cognition, and total scores. Hcy levels showed anegative correlation with processing speed, social cognition, and total MDD scores (P < 0.05). Hcy was alsosignificantly negatively correlated with Alistipes, Ruminococcae, Tenericides, and Porphyromonas (P < 0.05).CONCLUSIONOur results highlight that Hcy was correlated with cognition and gut microbiome in MDD. This interaction may berelated to the physiological and pathological mechanisms underlying cognitive deficits in depression.
