Efficacy and safety profile of repetitive transcranial magnetic stimulation versus modified electroconvulsive therapy in combination with antidepressants in patients with major depressive disorder / 四川精神卫生

BackgroundMajor depressive disorder is one of the most disabling mental diseases. Currently， medication in combination with physiotherapy and psychotherapy remains the most commonly used treatment modality for the disease， whereas only a few randomized controlled studies have been conducted on physiotherapy， and even fewer studies have focused on medication combined with physiotherapy. ObjectiveTo explore the efficacy and safety profile of repetitive transcranial magnetic stimulation （rTMS） versus modified electroconvulsive therapy （MECT） in combination with antidepressants in the treatment of major depressive disorder， so as to provide an optimized treatment plan for patients with major depressive disorder. MethodsPatients with major depressive disorder （n=335） hospitalized in Shandong Daizhuang Hospital from January 1， 2019 to April 30， 2023 were included， all of whom met the diagnostic criteria of the International Classification of Diseases， tenth edition （ICD-10）. Depending on their disease condition， patients were subjected to either MECT in combination with drugs （n=141） or rTMS in combination with drugs （n=194） after admission. Depressive symptoms were assessed using Hamilton Depression Scale-24 item （HAMD-24） at the baseline and the end of the 1st， 2nd， 3rd and 4th week of treatment， and the adverse reactions were documented in patient's medical records. ResultsAnalysis of variance on HAMD-24 revealed a significant effect of time （F=3.081， P=0.042）， but no effect of group （F=1.023， P=0.313）， and the interaction effect between the time and the groups was not statistically significant （F=1.642， P=0.191）. No statistical difference was reported between two groups in response rate and full remission rate （P>0.05）. Throughout the course of treatment， 58 cases （41.13%） of recent memory impairment and 74 cases （52.48%） of headache or neck muscle pain occurred in MECT combined with drugs group， and 27 cases （13.92%） in rTMS combined with drugs group experienced headache or head skin discomfort. ConclusionAntidepressants in combination with rTMS or MECT show equivalent efficacy in the treatment of major depressive disorder， while rTMS combined with antidepressants demonstrates a superior safety profile compared to MECT.

Abnormal Global Brain Functional Connectivity in MDD Patients with Childhood Trauma： A Resting-State fMRI Study / 中山大学学报(医学科学版)

ObjectiveChildhood trauma （CT） is considered one of the major risk factors for developing major depressive disorder （MDD） in adulthood. However， the neural basis of MDD patients with CT （CT-MDD） remains poorly understood. Therefore， the objective of our study is to explore the resting-state global brain functional connectivity （FC） in CT-MDD. MethodsA total of 34 CT-MDD and 34 healthy controls performed resting-state fMRI. Whole-brain voxel-level degree centrality （DC） analysis was performed， and the brain regions with significant differences between the two groups were selected as region of interest （ROI） for further estimating the global brain FC. Subsequently， correlation analysis was performed between DC values， FC values in abnormal brain areas and clinical characteristics. ResultsThe CT-MDD group showed increased DC value of the right middle frontal gyrus （MFG） compared with the healthy controls. Seed-based FC revealed that the CT-MDD group showed increased connections between the left precuneus and the right MFG or the right medial prefrontal cortex， relative to healthy controls （threshold at P<0.05）. Additionally， the DC value of the right MFG was correlated with the severity of CT. ConclusionOur results show the increased FC between the left precuneus and the ROI （right MFG） as well as the right medial prefrontal cortex， which are two important brain regions within the default mode network （DMN）， and might suggest increased synchronism between the cognitive executive networks and DMN in CT-MDD. These findings may provide insights into the pathophysiological mechanisms underlying CT-MDD.

Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis: A Systematic Review / 生物医学与环境科学（英文）

OBJECTIVE@#This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.@*METHODS@#We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression ( n = 113,154) and MDD ( n = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation.@*RESULTS@#The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that SLC6A4, GRIN2A, GRIN2C, SCN10A, and IL1B expression are associated with an increased risk of depression. In contrast, ADRB1, CHRNA3, HTR3A, GSTP1, and GABRG2 genes are candidate protective factors against depression.@*CONCLUSION@#This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.

Comparison and related factors of suicide risk among patients with schizophrenia,major depressive disorder,and bipolar disorder / 中国心理卫生杂志

Objective:To describe and analyze suicide risk of patients with schizophrenia,major depressive disorder,and bipolar disorder.Methods:A total of 2 016 patients with schizophrenia,903 patients with major de-pressive disorder,and 381 patients with bipolar disorder from inpatients,clinics,or communities who met the diag-nostic criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition were recruited.All patients were interviewed by psychiatrists using the Mini International Neuropsychiatric Interview to diagnose mental disor-ders and assess suicide risk,as well as Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)to as-sess symptoms.Differences and risk factors of suicide risk among three types of mental disorders were explored u-sing multivariate logistic regression analysis.Results:In the past one month,37 patients with schizophrenia(1.8％),516 patients with major depressive disorder(57.1％),and 102 patients with bipolar disorder(26.8％)had suicide risk.Compared with patients with schizophrenia,suicide risk in patients with major depressive disorder(OR=36.50)and bipolar disorder(OR=20.10)increased.Female(OR=1.87),smoking(OR=1.76),family history of suicide(OR=5.09),higher score of CRDPSS hallucination(OR=1.80),and higher score of CRDPSS depression(OR=1.54)were risk factors of suicide risk of patients.Conclusions:Suicide risk of patients with ma-jor depressive disorder and bipolar disorder is higher than that of patients with schizophrenia.In clinical practice,it is important to regularly assess suicide risk of patients.Patients who experience symptoms of hallucination and de-pression should be paid more attention to.

Disease costs in inpatients with schizophrenia,major depressive disorder,and bipolar disorder / 中国心理卫生杂志

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

Comparison of clinical characteristics between first-episode and relapse of major depressive disorder / 中国心理卫生杂志

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

A review of treatment delay for first-episode schizophrenia,first-episode major depressive disorder and first-episode bipolar disorder / 中国心理卫生杂志

This paper aims to review treatment delay in first-episode schizophrenia,depression,and bipolar disorder,and to compare related factors of treatment delay in the three first-episode mental disorders.It is found that increased patient responsibility,stigma,lack of disease-related knowledge,lack of access to resources,and insuffi-cient medical support lead to delay treatment,and making patients to have longer course,heavier symptoms,and lower social functions.

Effects of microglia in the pathogenesis of major depressive disorder / 中华行为医学与脑科学杂志

Major depressive disorder (MDD) has become an increasingly serious public health issue, characterized by high incidence and high disability rates. It often coexists with other mental health problems and physical diseases, with a significant negative impact on patients' quality of life. In clinical practice, MDD is considered a heterogeneous disease. The complexity of the pathological mechanisms and the variability in treatment responses lead to a lack of clear therapeutic targets, which complicates the treatment process. In recent years, with advancements in neuroscience, the crucial role of microglia in the pathogenesis of MDD has been revealed. As the main immune cells in the brain, microglia are not only involved in the regulation of neuroinflammation but also play important roles in neurogenesis and neuronal regulation in MDD. This article mainly discusses the role of microglia in the pathophysiological mechanisms of MDD, aiming to provide a theoretical basis for microglia as a potential target for the treatment of MDD.

Identification of genetic loci that overlap between major depressive disorder and insomnia using the conditional false discovery rate analysis / 四川精神卫生

BackgroundMajor depressive disorder and insomnia often coexist， and the two may share a mechanism of pathogenesis and be affected by common underlying genes with strong pleiotropic effects. Previous genome-wide association studies （GWAS） mainly focused on single-gene morphological characters analysis， which impose limitations on showing possible pleiotropic effects. ObjectiveTo identify genetic loci related to insomnia and major depressive disorder， and to examine whether there are common genetic factors underlying both insomnia and depression. MethodsThe GWAS data for major depressive disorder originates from the Psychiatric Genomics Consortium （PGC）， which comprises a total of 246 363 depressive cases and 561 190 controls. The insomnia GWAS data was downloaded from Sleep Disorder Knowledge Portal， involving 1 331 010 participants. Then the conditional false discovery rate （cFDR） and conjunction cFDR （ccFDR） were utilized to identify the genetic loci associated with major depressive disorder and insomnia， and pathway enrichment analysis was performed to examine the biological functions of these loci. ResultsA significant pleiotropic effect was detected between major depressive disorder and insomnia. By leveraging pleiotropic enrichment， 21 susceptibility loci （17 novel loci） for major depressive disorder and 38 susceptibility loci （28 novel loci） for insomnia were identified with the threshold of cFDR<0.01. A total of 16 pleiotropic loci （15 novel loci） related to both major depressive disorder and insomnia were identified with the threshold of ccFDR<0.05. pathway enrichment analysis indicated that the susceptibility loci were mainly enriched in synaptic transmission pathway， such as postsynaptic density （GO：0014069， P=4.91E-04， FDR=4.84E-03）， asymmetric synapse （GO：0032279， P=5.09E-04， FDR=4.84E-03）， and regulation of postsynaptic membrane neurotransmitter receptor levels （GO：0099072， P=5.11E-04， FDR=1.69E-02）. ConclusionA significant pleiotropic enrichment is found between major depressive disorder and insomnia， and the comorbidity mechanism is related to synaptic transmission. ［Funded by Tianjin Health Science and Technology Project （number， TJWJ2021QN065）； Tianjin Key Medical Discipline （Specialty） Construction Project （number， TJYXZDXK-033A）］

Correlation between functional connectivity of the precuneus and early efficacy to antidepressant treatment in patients of major depressive disorder / 四川精神卫生

BackgroundThe activity in precuneus within default mode network has been reported to be associated with antidepressant response， whereas the relationship between the functional network of precuneus and early response to antidepressant medications remains unclear. ObjectiveTo investigate the relationship between precuneus functional connectivity （FC） and early efficacy of antidepressant treatment in patients with major depressive disorder， so as to find a neurobiomarker to predict the early efficacy of antidepressants. MethodsA consecutive sample of 47 patients with major depressive disorder who attended the Mental Health Center， West China Hospital of Sichuan University from July 2017 to February 2019 and fulfilled the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited. Baseline resting-state functional magnetic resonance imaging scan findings and clinical assessments were recorded in participants. All patients treated with antidepressants for two weeks. Improvement was defined as 20% or greater reduction in baseline 16-item Quick Inventory of Depressive Symptoms Self-Report Scale （QIDS-SR16） by treatment exit， and patients were then classified into early improved group （n=27） and non-improved group （n=20）. FC values of precuneus and whole brain were calculated using bilateral precuneus as seed region， and baseline precuneus FC values were compared between two groups. Pearson correlation analysis was utilized to explore the correlation between FC values in brain regions with statistically significant differences and QIDS-SR16 total scores and reduction rates. ResultsFC values between the left precuneus and left precentral gyrus and between the right precuneus and right fusiform gyrus in early improved group were both higher than those in non-improved group （GRF correction， P<0.01）. The FC valves between the left precuneus and the left precentral gyrus and between the right precuneus and the right fusiform gyrus were positively correlated with QIDS-SR16 reduction rate （r=0.475， 0.297， P<0.05）. ConclusionWeakened FC between the left precuneus and left precentral gyrus and between the right precuneus and right fusiform gyrus are related to poor early efficacy to antidepressant treatment， and FC of precuneus may be a potential predictor of early response to antidepressants. ［Funded by the National Key Research & Development Program of China （number， 2016YFC1307204）； Key Development Project of the Sichuan Provincial Science and Technology Plan （number， 2018SZ0131）］

Higher IL-6 and IL-4 plasma levels in depressed elderly women are influenced by diabetes mellitus

Abstract Objective This study aimed at investigating a set of peripheral cytokines in elderly female patients with MDD, comparing them to controls, and assessing the potential influence of clinical comorbidities on inflammatory markers. Methods Twenty-five elderly female patients diagnosed with MDD and 19 age-matched female controls were enrolled on this study. Plasma levels of interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were evaluated with commercially-available assays. Results Elderly female patients with MDD exhibited higher plasma IL-6 and IL-4 levels when compared to controls. In a logistic regression model taking cytokine levels, comorbidities, and age into account, only type 2 diabetes mellitus (DM2) remained associated with MDD. Conclusion Diabetes influences the association between MDD and higher levels of cytokines in elderly female patients. Future studies should take this evidence into account in order to mitigate confounding factors.

Ansiedade e Depressão: rastreio entre profissionais da estratégia de saúde da família na Amazônia / Anxiety and Depression: screening among family health strategy professionals in the Amazon / Ansiedad y Depresión: tamizaje entre profesionales de estrategias de salud familiar en la Amazonía

Objetivo: realizar rastreamento de depressão e transtorno de ansiedade generalizada entre profissionais da Estratégia de Saúde da Família em um município no interior da Amazônia. Método:estudo transversal desenvolvido com 63 profissionais atuantes em 12 equipes de ESF na cidade de Santarém, Pará, Brasil. Foram utilizadas ferramentas validadas e adaptadas transculturalmente: o Patient ́s Health Questionaire ­9 e o Generalizes Anxiety Disorder ­7. Os dados foram analisados a partir de ferramentas da estatística descritiva (frequências absolutas e relativas) a partir do software Microsoft Excel 2018. Resultados:Houve predomínio de indivíduos do sexo feminino, na idade de 40 a 44 anos e raça/cor pardo. O estado civil predominante foi casado, a categoria profissional mais representada na amostra foram os agentes comunitários de saúde e o a maioria dos participantes possuía nível superior completo. 57.1% tiveram rastreamento positivo para depressão e 42.1% para ansiedade. Conclusão:Observou-se elevada frequência de ansiedade e depressão entre os profissionais incluídos na amostra. Nossos dados reforçam a necessidade de ações preventivas na área de saúde mental visando reduzir os impactos dos fatores de risco. Além disso, é fundamental a realização de grandes estudos voltados à investigação dos fatores associados à saúde mental dos trabalhadores da saúde no Brasil

Objective: To screen for depression and generalized anxiety disorder among Family Health Strategy professionals in a municipality in the interior of the Amazon. Method:A cross-sectional study was carried out with 63 professionals working in 12 FHS teams in the city of Santarém, Pará, Brazil. Cross-culturally adapted and validated tools were used: the Patient's Health Questionnaire -9 and the Generalized Anxiety Disorder -7. The data was analyzed using descriptive statistics tools (absolute and relative frequencies)using Microsoft Excel 2018 software. Results:There was a predominance of females, aged between 40 and 44 and of brown race/color. The predominant marital status was married, the most represented professional category in the sample were community health agents and the majority of participants had completed higher education. 57.1% were screened positive for depression and 42.1% for anxiety. Conclusion:There was a high frequency of anxiety and depression among the professionals included in the sample. Our data reinforces the need for preventive action in the area of mental health in order to reduce the impact of risk factors. In addition, it is essential to carry out large-scale studies investigating the factors associated with the mental health of health workers in Brazil.

Objetivo: Detectar depresión y ansiedad generalizada en profesionales de la Estrategia Salud de la Familia de un municipio del interior de la Amazonia. Método:Se realizó un estudio transversal con 63 profesionales que trabajan en 12 equipos de la ESF en la ciudad de Santarém, Pará, Brasil. Se utilizaron instrumentos validados y adaptados transculturalmente: el Cuestionario de Salud del Paciente -9 y el Trastorno de Ansiedad Generalizada -7. Los datos se analizaron mediante herramientas de estadística descriptiva (frecuencias absolutas y relativas) utilizando el software Microsoft Excel 2018. Resultados:Hubo un predominio de mujeres, con edades comprendidas entre 40 y 44 años y de raza/color moreno. El estado civil predominante fue casado, la categoría profesional más representada en la muestra fue la de agentes de salud comunitarios y la mayoría de los participantes habían completado estudios superiores. El 57,1% dieron positivo en depresión y el 42,1% en ansiedad. Conclusión:Hubo una elevada frecuencia de ansiedad y depresión entre los profesionales incluidos en la muestra. Nuestros datos refuerzan la necesidad de acciones preventivas en el área de la salud mental para reducir el impacto de los factores de riesgo. Además, es fundamental la realización de grandes estudios dirigidos a investigar los factores asociados a la salud mental de los trabajadores de la salud en Brasil

An electric field modeling study with meta-analysis to understand the antidepressant effects of transcranial direct current stimulation (tDCS)

Objective: Transcranial direct current stimulation (tDCS) has mixed effects for major depressive disorder (MDD) symptoms, partially owing to large inter-experimental variability in tDCS protocols and their correlated induced electric fields (E-fields). We investigated whether the E-field strength of distinct tDCS parameters was associated with antidepressant effect. Methods: A meta-analysis was performed with placebo-controlled clinical trials of tDCS enrolling MDD patients. PubMed, EMBASE, and Web of Science were searched from inception to March 10, 2023. Effect sizes of tDCS protocols were correlated with E-field simulations (SimNIBS) of brain regions of interest (bilateral dorsolateral prefrontal cortex [DLPFC] and bilateral subgenual anterior cingulate cortex [sgACC]). Moderators of tDCS responses were also investigated. Results: A total of 20 studies were included (21 datasets, 1,008 patients), using 11 distinct tDCS protocols. Results revealed a moderate effect for MDD (g = 0.41, 95%CI 0.18-0.64), while cathode position and treatment strategy were found to be moderators of response. A negative association between effect size and tDCS-induced E-field magnitude was seen, with stronger E-fields in the right frontal and medial parts of the DLPFC (targeted by the cathode) leading to smaller effects. No association was found for the left DLPFC and the bilateral sgACC. An optimized tDCS protocol is proposed. Conclusions: Our results highlight the need for a standardized tDCS protocol in MDD clinical trials. Registration number: PROSPERO CRD42022296246.

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

Introduction: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. Methods: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. Results: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. Conclusion: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Gravidade da depressão, resposta ao tratamento e PRO (incapacidade e QoL) em pacientes com DRT em um ano de acompanhamento com tratamento padrão: análise do subgrupo brasileiro do estudo observacional multinacional TRAL / Depression severity, treatment response and PRO (disability and QoL) in TRD patients over a 1-year follow-up with standard of care: Analysis of the Brazilian subset of the multicenter, observational TRAL study

Objetivo: A depressão resistente ao tratamento (DRT) é uma preocupação primária no Brasil devido à sua natureza onerosa e complexa, enquanto o diagnóstico e o tratamento geralmente são desafiadores. O presente manuscrito apresenta os resultados clínicos de um ano de acompanhamento em pacientes com DRT em tratamento padrão (SOC) no subgrupo brasileiro do estudo de Depressão Resistente ao Tratamento na América Latina (TRAL). Métodos: Essa fase longitudinal do estudo TRAL tinha como meta caracterizar alterações nos resultados clínicos e outras variáveis de interesse (p. ex., qualidade de vida, incapacidade) em um ano de acompanhamento em pacientes com DRT em 10 centros no Brasil. Os pacientes incluídos tinham diagnóstico clínico de DRT com base nos critérios DSM-5 e confirmado por MINI. A Escala de Depressão de Montgomery-Asberg (MADRS) era usada para avaliar a gravidade da doença e os resultados clínicos. Outras escalas de depressão e instrumentos classificados pelo paciente eram usadas para medir resultados correlacionados. Resultados: Cento e cinquenta e oito pacientes com DRT, na maioria mulheres (84,4%) com idade média de 48,55 anos, foram incluídos na análise. Apenas 31,4% dos pacientes apresentaram uma resposta clinicamente significativa, 10,3% tiveram recidiva e 26,7% alcançaram remissão, conforme medido pela MADRS no final do estudo (EOS). Aproximadamente 55% dos pacientes apresentavam depressão grave/moderadamente grave no EOS. Problemas de mobilidade, cuidados pessoais, problemas nas atividades usuais e dor e desconforto foram relatados pela maioria dos pacientes no EOS, assim como comprometimento marcado/extremo das atividades no trabalho/escola e da vida social/das atividades de lazer no EOS. Conclusões: Os resultados clínicos alcançados atualmente ainda são notavelmente insatisfatórios para DRT. Portanto, o envolvimento de todas as partes interessadas é essencial para implementar protocolos de tratamento mais eficazes no Brasil.

Objective: Treatment-resistant depression (TRD) is a primary concern in Brazil due to its burdensome and complex nature, while diagnosis and treatment is often challenging. The current manuscript presents the clinical outcomes in a one-year follow-up of TRD patients under Standard-of-care (SOC) in the Brazilian subset of the Treatment-Resistant Depression in America Latina (TRAL) study. Methods: This longitudinal phase of TRAL aimed to characterize changes in the clinical outcomes and other variables of interest (e.g. quality of life, disability) in a one-year follow-up of TRD patients in 10 centers in Brazil. Included patients were clinically diagnosed with TRD based on DSM-5 criteria and confirmed by MINI. Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess disease severity and clinical outcomes. Other depression scales and patient rated instruments were used to measure correlated outcomes. Results: One hundred fifty-eight TRD patients, mostly female (84.4%), averaging 48.55 years, were included in the analysis. Only 31.4% of the patients showed a clinically significant response, 10.3% had a relapse and 26.7% achieved remission, as measured through MADRS at end-of-study (EOS). Almost 55% of the patients showed moderately severe/severe depression at EOS. Mobility issues, self-care, problems with usual activities and pain and discomfort were reported by the majority of the patients at EOS, as well as marked/extreme disruption of school/work and social life/leisure activities at EOS. Conclusions: Currently achieved clinical outcomes are still remarkably unsatisfactory for TRD. Therefore, the involvement of all relevant stakeholders is essential to implement more effective treatment protocols in Brazil.

Positive screening for major depressive disorder in high-risk pregnant women / Triagem positiva para transtorno depressivo maior em gestantes de alto risco

ABSTRACT Objective: To estimate the frequency of positive screening for major depressive disorder and associated factors in high-risk pregnant women at a reference hospital of the Brazilian Public Health System. Methods: Cross-sectional study with 184 high-risk pregnant women at the Maternity at the Hospital Regional de São José , SC, Brazil. Positive screening for major depressive disorder using the Edinburgh Postpartum Depression Scale was selected as the dependent variable. Socio-demographic and pregnancy-related variables were also collected. Data were analyzed using Poisson regression with a robust estimator, including all variables that presented a p-value < 0.20 in the bivariate analysis. Statistically significant differences were considered when p ≤ 0.05. Results: The frequency of positive screening for major depressive disorder was 37.5%. Non-white skin color, income of less than USD 572,56 per month and maternal age of less than 18 years or greater than or equal to 35 years were statistically and independently associated with positive screening for major depressive disorder in high-risk pregnant women. Conclusion: The frequency of positive screening for major depressive disorder in the high-risk pregnant women studied was 37.5%. The frequency was statistically associated with skin color, family income and extremes in the maternal age.

RESUMO Objetivo: Estimar a frequência de rastreio positivo de transtorno depressivo maior e fatores associados em gestantes de alto risco em uma maternidade de referência do Sistema Único de Saúde. Métodos: Estudo transversal envolvendo 184 gestantes de alto risco da Maternidade do Hospital Regional de São José, SC, Brasil. A variável dependente foi o rastreio de transtorno depressivo maior por meio da aplicação da Escala de Depressão Pós-parto de Edimburgo. Foram coletadas ainda variáveis sociodemográficas e relacionadas à gestação. Os dados foram analisados por meio da regressão de Poisson com estimador robusto, incluindo todas as variáveis que apresentaram valor de p < 0,20 na análise bivariada. Consideraram-se diferenças estatisticamente significativas quando p ≤ 0,05. Resultados: A frequência de rastreio positivo para transtorno depressivo foi de 37,5%. Cor da pele não branca, renda mensal inferior a USD 572,56 e idade materna inferior a 18 anos ou superior ou igual a 35 anos foram estatística e independentemente associadas ao rastreamento positivo para transtorno depressivo maior em gestantes de alto risco. Conclusão: A frequência de rastreio positivo de transtorno depressivo maior em gestantes de alto risco estudadas foi de 37,5%. A frequência mostrou-se estatisticamente associada com cor de pele, renda familiar e extremos de idade materna.

A Comprehensive Overview of the Role of Visual Cortex Malfunction in Depressive Disorders: Opportunities and Challenges / 神经科学通报·英文版

Major depressive disorder (MDD) is a highly heterogeneous mental disorder, and its complex etiology and unclear mechanism are great obstacles to the diagnosis and treatment of the disease. Studies have shown that abnormal functions of the visual cortex have been reported in MDD patients, and the actions of several antidepressants coincide with improvements in the structure and synaptic functions of the visual cortex. In this review, we critically evaluate current evidence showing the involvement of the malfunctioning visual cortex in the pathophysiology and therapeutic process of depression. In addition, we discuss the molecular mechanisms of visual cortex dysfunction that may underlie the pathogenesis of MDD. Although the precise roles of visual cortex abnormalities in MDD remain uncertain, this undervalued brain region may become a novel area for the treatment of depressed patients.

Effect of electroconvulsive therapy on brain functional network in major depressive disorder / 生物医学工程学杂志

Electroconvulsive therapy (ECT) is an interventional technique capable of highly effective neuromodulation in major depressive disorder (MDD), but its antidepressant mechanism remains unclear. By recording the resting-state electroencephalogram (RS-EEG) of 19 MDD patients before and after ECT, we analyzed the modulation effect of ECT on the resting-state brain functional network of MDD patients from multiple perspectives: estimating spontaneous EEG activity power spectral density (PSD) using Welch algorithm; constructing brain functional network based on imaginary part coherence (iCoh) and calculate functional connectivity; using minimum spanning tree theory to explore the topological characteristics of brain functional network. The results show that PSD, functional connectivity, and topology in multiple frequency bands were significantly changed after ECT in MDD patients. The results of this study reveal that ECT changes the brain activity of MDD patients, which provides an important reference in the clinical treatment and mechanism analysis of MDD.

Research progress of anti-inflammatory agents in the treatment of major depressive disorder / 四川精神卫生

Major depressive disorder is one of the common mental disorders， and its pathogenesis is not yet fully understood. Elevated levels of inflammation are recognized as one of the mechanisms contributing to the onset of major depressive disorder. Numerous studies have indicated that non-steroidal anti-inflammatory drugs， omega-3 fatty acids， statins， pioglitazone， minocycline， N-acetylcysteine， corticosteroids and other medications may exert anti-depressant effects through their anti-inflammatory actions. This article provides a comprehensive review of the application of these drugs in the treatment of major depressive disorder， exploring the therapeutic effects and potential mechanisms of action of different anti-inflammatory agents， thereby offering a reference for the future application of anti-inflammatory interventions in the treatment of depression. ［Funded by The Ministry of Science and Technology of the People's Republic of China （Number， 2022ZD0211700）］

Comparison of serum kynurenine pathway metabolites between patients with first-episode and recurrent major depressive disorder / 四川精神卫生

BackgroundThe pathogenesis of depression remains not fully understood， and previous studies have suggested that the kynurenine pathway （KP） plays an important role in the pathogenesis of major depressive disorder. ObjectiveTo study the difference in serum KP metabolites level between patients with first-episode and recurrent major depressive disorder， and to testify the correlation between KP metabolites level with the severity of depressive symptoms， so as to provide references for the prevention of recurrence. MethodsA total of 136 patients with major depressive disorder who attended the outpatient clinics of the Affiliated Brain Hospital of Guangzhou Medical University from November 2016 to December 2018 and met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria were included， including 62 patients in the first-episode group and 74 patients in the recurrent group. Meanwhile， 60 healthy subjects were included as control group. All patients were assessed by Hamilton Depression Scale-17 item （HAMD-17）， and serum concentrations of tryptophan （TRP）， kynurenine （KYN） and kynurenic acid （KYNA） were measured by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Then the correlation of HAMD-17 total score and individual item scores with the levels of KP metabolites was tested using partial correlation coefficient. ResultsCompared with the control group， the first-episode group and recurrent group showed a marked decline in TRP concentration （t=-3.044， -4.477， P<0.05 or 0.01） and an increase in KYN/TRP ratio （t=2.343， 3.644， P<0.05 or 0.01）， with significant differences. The KYNA concentrations （t=2.490， 2.636， P<0.05 or 0.01） and KYNA/KYN ratio （t=2.894， 2.616， P<0.01） in first-episode group and control group were notably elevated compared to recurrent group， with statistical difference. Partial correlation analysis in patients with first-episode major depressive disorder demonstrated that KYN/TRP ratio was positively correlated with the HAMD-17 anxiety/somatization factor score （r=0.261， P<0.05）， and KYNA/KYN ratio was negatively correlated with HAMD-17 total score and block factor score （r=-0.286， -0.282， P<0.05）. In patients with recurrent major depressive disorder， KYN/TRP ratio was positively correlated with HAMD-17 anxiety/somatization factor score （r=0.280， P<0.05）. ConclusionKP metabolites in serum differ between first-episode and recurrent major depressive disorder patients， and patients with recurrent episodes experience severe KP metabolite abnormalities. Therefore， KP metabolites are considered to be potential biomarker candidates to assist clinicians in the diagnosis and recurrent prediction of major depressive disorder. ［Funded by National Key Research and Development Program Precision Medicine Research Project （number， 2016YFC0906300）］