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.

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）］

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）］

White Matter Damage in Major Depressive Disorder and TCM Treatment： A Review / 中国实验方剂学杂志

At present， major depressive disorder （MDD） is highly prevalent with advanced neurological disorders as the main pathological manifestations. As the physiological function bearer of higher neural activity， gray matter has become the focus of MDD treatment. However， recent research has shown that white matter and gray matter are independent of each other in the central nervous system （CNS）， and their functions are integrated and linked. In addition to gray matter damage， white matter damage is also the core driving event of disease progression and determines the outcome of MDD. At the treatment level， the current drug treatment of MDD mainly focuses on gray matter repair， while ignoring the importance of white matter integrity for the treatment of the disease， which has become the weakness of the current treatment of MDD. Traditional Chinese medicine （TCM） has good application potential in white matter repair. This paper elaborated on the following three aspects. ① The roles of white matter damage in the occurrence and development of MDD were summarized. ② The key link of white matter repair in MDD was elaborated with microglia microenvironment regulation as the entry point. ③ The application value of TCM in white matter repair in MDD was analyzed. This review aims to highlight the importance of white matter integrity in the treatment of MDD and is expected to expand the understanding dimension of the activity of related Chinese medicines in MDD from the perspective of white matter repair and analyze its potential application value.

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.

Alterações de sono em pacientes depressivos adultos: uma revisão integrativa / Sleep changes in adult depressive patients: an integrative review / Cambios del sueño en pacientes depresivos adultos: una revisión integradora

Esta é uma revisão da literatura que tem como objetivo elucidar as alterações do sono em pacientes adultos com depressão, principalmente sem outras comorbidades ou condições especiais, e estabelecer a relação entre distúrbios do sono e depressão, com foco no Transtorno Depressivo Maior. A metodologia envolve uma revisão integrativa da literatura dos últimos 15 anos (2009-2023) nas bases de dados Biblioteca Virtual em Saúde (BVS) e Pubmed, utilizando as palavras-chave "distúrbios do sono", "depressão" e "adultos". Os resultados mostram um total de 240 artigos, dos quais 26 foram selecionados e 12 foram incluídos na análise. A discussão destaca o interesse recente em estudar as associações entre distúrbios do sono e transtornos depressivos, bem como a natureza global da pesquisa. A relação entre sono e saúde mental, bem como a classificação e relação entre distúrbios do sono, também são discutidos. Os achados indicam que distúrbios do sono são prevalentes em pacientes com depressão, sendo a insônia um fator de risco significativo para o desenvolvimento da depressão. A relação bidirecional entre sono e depressão é destacada, com a depressão afetando o sono e o sono afetando a depressão. A importância de estudar os mecanismos por trás dessa relação é enfatizada, pois pode ajudar os psiquiatras a gerenciar de forma mais eficaz a comorbidade de depressão e distúrbios do sono. O tratamento adequado dos distúrbios do sono também pode desempenhar um papel vital na melhoria do prognóstico e na prevenção da recorrência da depressão.

This is a literature review that aims to elucidate the sleep alterations in adult patients with depression, primarily without other comorbidities or special conditions, and establish the relationship between sleep disturbances and depression, with a focus on Major Depressive Disorder. The methodology involves an integrative review of the literature from the last 15 years (2009-2023) on the databases Biblioteca Virtual em Saúde (BVS) and Pubmed, using the keywords "sleep disorders," "depression," and "adults." The results show a total of 240 articles, 26 of which were selected and 12 of which were included in the analysis. The discussion highlights the recent interest in studying the associations between sleep disturbances and depressive disorders, as well as the global nature of the research. The relationship between sleep and mental health, as well as the classification and relationship between sleep disturbances, are also discussed. The findings indicate that sleep disturbances are prevalent in patients with depression, with insomnia being a significant risk factor for the development of depression. The bidirectional relationship between sleep and depression is highlighted, with depression affecting sleep and sleep affecting depression. The importance of studying the mechanisms behind this relationship is emphasized, as it can help psychiatrists manage the comorbidity of depression and sleep disturbances more effectively. Adequate treatment of sleep disturbances may also play a vital role in improving the prognosis and preventing the recurrence of depression.

Esta es una revisión de la literatura que tiene como objetivo dilucidar las alteraciones del sueño en pacientes adultos con depresión, principalmente sin otras comorbilidades o condiciones especiales, y establecer la relación entre las alteraciones del sueño y la depresión, con un enfoque en el Trastorno Depresivo Mayor. La metodología consiste en una revisión integradora de la literatura de los últimos 15 años (2009-2023) en las bases de datos Biblioteca Virtual em Saúde (BVS) y Pubmed, utilizando las palabras clave "sleep disorders," "depression," y "adults." Los resultados muestran un total de 240 artículos, de los cuales 26 fueron seleccionados y 12 incluidos en el análisis. La discusión destaca el reciente interés por estudiar las asociaciones entre las alteraciones del sueño y los trastornos depresivos, así como el carácter global de la investigación. También se analiza la relación entre el sueño y la salud mental, así como la clasificación y la relación entre los trastornos del sueño. Los resultados indican que las alteraciones del sueño son prevalentes en pacientes con depresión, siendo el insomnio un factor de riesgo significativo para el desarrollo de la depresión. Se destaca la relación bidireccional entre sueño y depresión, en la que la depresión afecta al sueño y el sueño a la depresión. Se subraya la importancia de estudiar los mecanismos que subyacen a esta relación, ya que puede ayudar a los psiquiatras a gestionar la comorbilidad de la depresión y los trastornos del sueño de forma más eficaz. El tratamiento adecuado de los trastornos del sueño también puede desempeñar un papel vital en la mejora del pronóstico y la prevención de la recurrencia de la depresión.

Randomized clinical trial on the efficacy of a new transcranial direct current stimulation (tDCS) device in the treatment of depression: a low-cost option for developing countries? / Ensaio clínico randomizado sobre a eficácia de novo equipamento de estimulação transcraniana por corrente contínua (ETCC) no tratamento da depressão: uma opção de baixo custo para países em desenvolvimento?

ABSTRACT Objective: Verify the clinical efficacy and safety of a low-cost tDCS device, in a clinical trial for major depressive disorder. Methods: 168 persons were recruited; 32 depressed individuals with moderate or severe depressive symptoms (HDRS17 scores higher than 18) were included and randomized for the trial (16 individuals in each group). The intervention consisted of 10 active anodal tDCS sessions at 2 mA for 30 minutes over the left dorsolateral prefrontal cortex; or sham. The main outcome was HDRS17; secondary outcomes included satisfaction (TSQM II) and quality of life (WHOQOL-BREF). Assessments at baseline, endpoint and at 30 days follow-up. Results: The sample was composed by a total of 11 men and 21 women, mean age of 42.75 years (95% CI: 38.10-47.40). Active treatment was superior than sham: There was a significant interaction between group and time regarding HDRS-17 scores (F = 4.089, df = 2, p = 0.029; partial Eta squared = 0. 239). Post hoc analyses exhibited a statistically significant difference between active and sham group symptoms after a 30 days follow-up (difference = -7.75, p = 0.008, Cohen's d = 1.069). There were 3 dropouts, all in the active group, due schedule issues. No severe adverse effects reported. Conclusion: The current active tDCS protocol was related with clinical improvement of depressive symptoms. Intervention was well-tolerated. Non-invasive brain stimulation techniques are still not routinely used, although a viable strategy for treatment-resistant patients, partial responders and people unable to use pharmacological treatment. We aim to increase knowledge and use of tDCS for the Brazilian population.

RESUMO Objetivo: Testar a eficácia clínica e a segurança de equipamento de estimulação elétrica transcraniana por corrente contínua (ETCC) de baixo custo em ensaio clínico para transtorno depressivo maior (TDM). Métodos: Foram recrutadas 168 pessoas e incluídos e randomizados 32 indivíduos com depressão moderada ou grave (escores na HDRS17 >18; 16 indivíduos em cada grupo). A intervenção consistiu de 10 sessões de ETCC ativa a 2 mA no córtex pré-frontal dorsolateral esquerdo por 30 minutos, ou sham. O desfecho principal foi HDRS17; os desfechos secundários foram satisfação (TSQM II) e qualidade de vida (WHOQOL-BREF). Avaliações no início, no final do tratamento e após 30 dias de seguimento. Resultados: A amostra foi composta de 11 homens e 21 mulheres, com idade média de 42,75 anos (IC 95%: 38,10 a 47,40). O tratamento ativo foi superior ao sham: houve interação significativa entre grupo e tempo em relação aos escores de HDRS17 na ANOVA (F = 4,089, df = 2, p = 0,029; partial Eta squared = 0,239). A análise post hoc mostrou diferença significativa na HDRS17 no follow-up após 30 dias (diferença = -7,75, p= 0,008, Cohen's d = 1,069). Houve 3 dropouts, todos no grupo ativo, devido a problemas de agenda. Não houve registro de efeitos adversos graves. Conclusão: O tratamento ativo teve relação com melhora clínica de sintomas depressivos. A intervenção foi bem tolerada. Técnicas de estimulação cerebral não invasivas ainda não são rotina na prática clínica, apesar de estratégias viáveis para pacientes resistentes a tratamento, respondedores parciais e pessoas com intolerância a medicamentos. Esperamos ampliar o conhecimento e o uso de protocolos de ETCC na população brasileira.

Influência das variantes genéticas do gene IL6 no transtorno depressivo maior: uma revisão / nfluence of IL6 gene genetic variants on major depressive disorder: a review / Influencia de las variantes genéticas del gen IL6 en el trastorno depresivo mayor: una revisión

Objetivo:Elucidar o quadro clínico do transtorno depressivo maior (TDM) e verificar a associação dessa condição com polimorfismos do gene IL6. Método:Tratou-se de uma revisão sistemática com a busca de artigos originais nas bases de dados Scopus, Web of Science, PubMed e BVS, os quais trouxeram informações sobre variantes genéticas que tinham relação com polimorfismos do gene IL6. Estudos que não apresentaram dados completos, inclusive dados estatísticos, revisões, meta-análises e resumos, foram excluídos. Resultados:Foram encontrados 54 artigos nas bases de dados. Utilizou-se a plataforma Rayyan para retirar as duplicatas e ler os resumos para seleçãoinicial. Restaram 12 artigos, onde os que eram de acesso livre foram encaminhados para leitura completa, totalizando 5 artigos para essa revisão. Conclusão:Evidências sugerem uma condição sistêmica no TDM e dados demonstram alterações inflamatórias. Dadoque na maior parte dos estudos pacientes com TDM tiveram estados inflamatórios mais elevados, parece haver relação entre a IL-6 e o transtorno. A IL-6 induz alterações no cérebro, ativação de microglia e controla a saúde dos neurônios, podendo tornar tangível uma relação dos polimorfismos com a doença, mas ainda não existem muitos estudos na área

Objective:To elucidate the clinical picture of major depressive disorder (MDD) and to verify the association of this condition with polymorphisms of the IL6 gene. Method:This was a systematic review with the search of original articles in the databases Scopus, Web of Science, PubMed and VHL, which brought information about genetic variants that were related to polymorphisms of the IL6 gene. Studies that did not present complete data, including statistical data, reviews, meta-analyses and abstracts, were excluded. Results:A total of 54 articles were found in the databases. The Rayyan platform was used to remove the duplicates and read the abstracts for initial selection. There were 12 articles, where those that were freely accessible were sent for full reading, totaling 5 articles for this review. Conclusion:Evidence suggests a systemic condition in MDD and data demonstrate inflammatory changes. Given that in most studies patients with MDD had higher inflammatory states, there seems to be a relationship between IL-6 and the disorder. IL-6 induces changes in the brain, activation of microglia and controls the health of neurons, and may make tangible a relationship between polymorphisms and the disease, but there are not many studies in the area.

Objetivo: Dilucidar el cuadro clínico del trastorno depresivo mayor (TDM) y verificar la asociación de esta condición con polimorfismos del gen IL6. Método: Se trata de una revisión sistemática con búsqueda de artículos originales en las bases de datos Scopus, Web of Science, PubMed y BVS, que aportaron información sobre variantes genéticas relacionadas con polimorfismos del gen IL6. Se excluyeron los estudios que no presentaron datos completos, incluidos datos estadísticos, revisiones, metanálisis y resúmenes. Resultados:Se encontraron un total de 54 artículos en las bases de datos. La plataforma Rayyan se utilizó para eliminar los duplicados y leer los resúmenes para la selección inicial. Hubo 12 artículos, donde aquellos que eran de libre acceso fueron enviados para lectura completa, totalizando 5 artículos para esta revisión. Conclusión:La evidencia sugiere una condición sistémica en el TDM y los datos demuestran cambios inflamatorios. Dado que en la mayoría de los estudios los pacientes con TDM tenían estados inflamatorios más altos, parece haber una relación entre la IL-6 y el trastorno. La IL-6 induce cambios en el cerebro, la activación de la microglía y controla la salud de las neuronas, y puede hacer tangible una relación entre los polimorfismos y la enfermedad, pero no hay muchos estudios en el área.

Major depressive disorder as a risk factor for suicidal ideation for attendees of educational institutions: a meta-analysis and meta-regression / Transtorno depressivo maior como fator de risco para ideação suicida em alunos de instituições educacionais: uma metanálise e metarregressão

Abstract Objective: This study aimed to analyze the effect of major depressive disorder (MDD) as a risk factor for suicidal ideation in individuals whose ages varied from 11 to 24 years and who were attending educational institutions. Data source: A systematic review was carried out by searching in PubMed and Biblioteca Virtual em Saúde (BVS). Original studies conducted in educational institutions, including individuals whose age varied from 11 to 24 years, in English, Spanish, or Portuguese were included. Data synthesis: Eight studies were selected for the meta-analysis, including 35,443 youths, with an average age of 16.8 years, predominantly female (51.2%), and from middle-income Asian countries (91.6%). An odds ratio of MDD of 3.89 (95%CI 2.46-6.17) for suicide ideation in youth was found. Subgroup analysis showed higher effects in Asia (OR=4.71; 95%CI 3.22-6.89) than Americas (OR=1.71; 95%CI 1.44-2.03). The meta-regression model indicated that younger adolescents (coef=-0.63; 95%CI 1.09--0.18; p<0.01) and older studies (coef=-0.23; 95%CI 0.039--0.08; p<0.01) presented higher effects of MDD on suicidal ideation. Conclusions: Early detection and treatment of MDD in youth patients are of utmost importance for preventing suicidal ideation. Educational institutions could play an important role in the early detection and intervention.

Resumo Objetivo: Analisar o efeito do transtorno depressivo maior (TDM) como fator de risco para a ideação suicida em indivíduos com idades entre 11 e 24 anos que frequentam instituições de ensino. Fontes de dados: Revisão sistemática realizada até agosto de 2020 por meio de buscas nas bases United States National Library of Medicine (PubMed) e Biblioteca Virtual em Saúde (BVS), sem limitações quanto à data de publicação. Síntese dos dados: Oito estudos foram selecionados para a metanálise, incluindo 35.443 jovens com idade média de 16,8 anos, predominantemente do sexo feminino (51,2%) e de países asiáticos de renda média (91,6%). Foi encontrado odds ratio (OR) de TDM de 3,89 (intervalo de confiança — IC95% 2,46-6,17) para a ideação suicida em jovens. A análise de subgrupo mostrou efeitos maiores na Ásia (OR=4,71; IC95% 3,22-6,89) do que nas Américas (OR=1,71; IC95% 1,44-2,03). O modelo de metarregressão demonstrou que adolescentes mais jovens (coef=-0,63; IC95% -1,09--0,18; p＜0,01) e estudos mais antigos (coef=-0,23; IC95% -0,039--0,08; p＜0,01) apresentaram maiores efeitos do TDM sobre a ideação suicida. Conclusões: Observou-se relação entre TDM e ideação suicida no continente asiático, entre adolescentes mais jovens e em estudos mais antigos.

Brain-derived neurotrophic factor serum levels following ketamine and esketamine intervention for treatment-resistant depression: secondary analysis from a randomized trial

Abstract Objectives Evidence suggests that ketamine's influence on brain-derived neurotrophic factor (BDNF) might be involved in its mechanism of rapid antidepressant action. We aimed to evaluate the differential impact of ketamine and esketamine on serum BDNF levels and its association with response patterns in treatment-resistant depression (TRD). Methods Participants (n = 53) are from a randomized, double-blind clinical trial comparing the efficacy of single-dose ketamine (0.5mg/kg, n = 27) and esketamine (0.25mg/kg, n = 26) in TRD. Depression severity was assessed before and 24 hours, 72 hours, and 7 days after the intervention, using the Montgomery-Åsberg Depression Rating Scale (MADRS). Blood samples were collected before infusion, 24 hours, and 7 days afterwards. Results There were no significant changes in BDNF levels at post-infusion evaluation points, and no difference in BDNF levels comparing ketamine and esketamine. Both drugs exhibited similar therapeutic effect. There was no association between BDNF levels and response to treatment or severity of depressive symptoms. Conclusion There was no significant treatment impact on BDNF serum levels - neither with ketamine nor esketamine - despite therapeutic response. These results suggest that ketamine or esketamine intervention for TRD has no impact on BDNF levels measured at 24 hours and 7 days after the infusion. This clinical trial is registered on the Japan Primary Registries Network: UMIN000032355.

Effect of mentalization-based family therapy on depressive symptoms and non-suicidal self-injury behavior in adolescents with major depressive disorder / 四川精神卫生

BackgroundThe major depressive disorder has high prevalence among adolescents， and non-suicidal self-injury （NSSI） behaviors frequently occur among patients， therefore， major depressive disorder in adolescents has become the researching focus. ObjectiveTo explore the effect of mentalization-based family therapy （MBFT） on depressive symptoms and NSSI behavior in adolescents with major depressive disorder， and to provide references for the rehabilitation of major depressive disorder in adolescents. MethodsA total of 90 adolescent patients with major depression disorder who met the diagnostic criteria of International Classification of Diseases， 10th edition （ICD-10） for depressive disorders and attended Wuhan Mental Health Center from January to December 2022 were selected， and were assigned into study group （n=44） and control group （n=46） using random number table method. All participants received routine intervention， based on this， study group added a 60-minute MBFT intervention once a week for 8 weeks. Before the intervention and at the end of 1st， 2nd，4th and 8th week，the two groups were assessed using Hamilton Depression Scale-24 item （HAMD-24）， General Self-Efficacy Scale （GSES）， Pittsburgh Sleep Quality Index （PSQI） and Ottawa Self-injury Inventory （OSI）. ResultsThe repeated measures analysis of variance reported a statistical main effect of time， main effect of group， and interaction effect between time and group at the baseline and the end of 1st， 2nd， 4th and 8th week of treatment in HAMD-24 score （F=69.621， 15.428， 29.623， P˂0.05）， OSI score （F=176.642， 37.682， 21.873， P˂0.05）， GSES score （F=215.236， 57.421， 27.857， P˂0.05） and PSQI score （F=268.541， 61.863， 33.867， P˂0.05）. Individual effect analysis discovered a statistical difference between study group and control group at the end of 2nd， 4th and 8th week of treatment in HAMD-24 score （t=5.567， 8.645， 6.233， P˂0.01）， OSI score （t=3.675， 11.817， 9.632， P˂0.01）， GSES score （t=23.462， 31.709， 12.750， P˂0.01） and PSQI score （t=9.664， 22.457， 9.333， P˂0.01）. ConclusionMBFT may improve depressive symptoms， NSSI behavior， sleep quality and self-efficacy in adolescents with major depressive disorder. ［Funded by 2022 Natural Science Foundation Project of Hubei Province （number， 2022CFB483）］

Correlation of psychomotor retardation with plasma G-CSF and M-CSF levels in patients with major depressive disorder / 四川精神卫生

BackgroundThe etiopathogenesis of major depressive disorder （MDD） is strongly associated with neuroinflammation. MDD is a highly heterogeneous psychiatric disorder， and the disease subtyping is an essential step for the identification of biological markers. The presence of psychomotor retardation seriously affects the prognosis of MDD， whereas the underlying mechanism is not yet completely clear. A potential involvement of granulocyte colony-stimulating factor （G-CSF） and macrophage colony-stimulating factor （M-CSF） in the pathogenesis of MDD with psychomotor retardation has been suggested in previous studies， but little detailed research has been completed. ObjectiveTo analyze the correlation of plasma G-CSF and M-CSF levels with psychomotor retardation in patients with MDD， and to explore the potential biological underpinnings of psychomotor retardation in MDD. MethodsA total of 50 MDD patients who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） and attended the outpatient clinics of Shanghai Mental Health Center from April 2018 to April 2019 were included. The severity of symptoms was assessed using the Hamilton Depression Scale-17 item （HAMD-17）. According to the retardation factor in HAMD-17， patients with a score of ≥8 were included in retardation group （n=22）， and those with a score below 8 were included in non-retardation group （n=28）. Another 22 age- and sex-matched healthy controls were concurrently recruited. Plasma G-CSF and M-CSF levels were measured in all subjects using Luminex liquid suspension chip technology. Spearman correlation analysis was adopted to verify the correlation of retardation factor score in HAMD-17 with plasma G-CSF and M-CSF levels in MDD patients. ResultsPlasma G-CSF levels were decreased in MDD patients compared with healthy controls ［57.34（39.24， 83.15）pg/mL vs. 71.47（61.20， 79.99）pg/mL， Z=-2.098， P<0.05］. A statistical difference was found in plasma G-CSF level ［63.92（54.60， 89.43）pg/mL vs. 47.80（33.41， 74.66）pg/mL vs. 71.47（61.20， 79.99）pg/mL， H=8.247， P=0.016］ and plasma M-CSF level ［20.05（16.05， 22.23）pg/mL vs. 13.05（11.43， 17.50）pg/mL vs. 18.95（14.59， 22.88）pg/mL， H=7.620， P=0.022］ among retardation group， non-retardation group and healthy control group. The post hoc pairwise comparisons using Bonferroni correction indicated that plasma G-CSF level was lower in non-retardation group compared with healthy control group （adjusted P<0.05）， and plasma M-CSF level was higher in retardation group compared with non-retardation group （adjusted P<0.05）. The retardation factor score in HAMD-17 was positively correlated with plasma M-CSF level in MDD patients （r=0.348， P<0.05）. ConclusionThe prevalence of psychomotor retardation in MDD patients may be related to abnormally elevated plasma M-CSF level. ［Funded by Shanghai "Science and Technology Innovation Action Plan" Project in Medical Innovation Research Field （number， 21Y11905600）； Shanghai "Science and Technology Innovation Action Plan" Project in Natural Science Field （number， 21ZR1455100）； Shanghai Mental Health Center Scientific Research Project （number， 2021-YJ02）］

The association of obesity with depressed severity in adolescent patients with first-episode untreated major depressive disorder / 中华行为医学与脑科学杂志

Objective:To investigate the characteristics of obesity in adolescents with major depressive disorder (MDD) and its association with the depressed severity.Methods:A total of 278 adolescents with MDD were recruited according to the inclusion and exclusion criteria. Their demographic data were collected and 24-item Hamilton depression scale (HAMD-24) was used to evaluate their severity of depression. According to the body mass index (BMI) classification standard of adolescents in China, all subjects were classified into four groups(wasting group, normal BMI group, overweight group and obesity group). SPSS 26.0 statistical software was used for data analysis. The Kruskal-Wallis test and the Chi-square test were separately used for the comparison of the four groups.Spearman correlation was used to explore the relationship between BMI and HAMD-24 scores and severity.Results:Among 278 adolescents with MDD, the prevalence of body abnormality was 32.4% (90/278), among which wasting, overweight and obesity were 9.0% (25/278), 14.4% (40/278) and 9.0% (25/278) respectively. There were statistically differences in gender ( χ2=17.018, P<0.001), HAMD-24 scores ( H=9.427, P=0.024) and depressed severity( H=8.508, P=0.037) among the four groups. Multiple comparisons showed that there were only statistically differences between obesity group and normal BMI group, that was the prevalence of obesity in males was higher than that in females ( χ2=13.631, P<0.001), and the level in HAMD-24 scores ( Z=2.956, P=0.003) and depressed severity ( Z=2.832, P=0.005) was lower in obesity group than that in normal BMI group.Spearman correlation analysis showed that BMI was negatively correlated with HAMD-24 scores ( r=-0.162, P=0.007). Conclusion:There is gender difference in obesity rates among the adolescent patients with first-episode untreated MDD. And the obese patients are less depressed than those with normal BMI.

Comparation of resting brain regional homogeneity between patients with major depressive disorder and their healthy siblings / 中华行为医学与脑科学杂志

Objective:To explore differences of resting brain regional homogeneity (ReHo) between patients with major depressive disorder (MDD) and their siblings.Methods:From January to December 2013, the resting-state functional magnetic resonance imaging (fMRI) data of 87 patients with MDD and 21 healthy siblings were collected.DPABI v5.1 software was used to preprocess the resting-state fMRI data, and ReHo maps of each subject was obtained. A two-sample t-test was used to compare differences between the patients with MDD and their siblings in ReHo values throughout the brain. ReHo values within the significant brain regions were extracted out, and used to calculate Spearman correlation with the total score of 17-items Hamilton depression rating scale(HAMD-17) in the patients with MDD and their siblings respectively.The software of SPSS 20.0 was used for statistical analysis. Results:The patients with MDD exhibited lower ReHo values in the precuneus extending to the posterior cingulate cortex (PCu/PCC) compared with their siblings (cluster-size=126 voxel, cluster-level PFDR=0.033; MNI: x=-4, y=-58, z=38, t=4.30). ReHo values of the PCu/PCC in patient with MDD were positively correlated with the severity of depressive symptoms ( r=0.255, P=0.021). Conclusion:Compared with the siblings, local brain activity of the PCu/PCC in the patients with MDD was decreased, and related to the severity of depressive symptoms. It is helpful to further reveal the intrinsic neural mechanism of MDD.

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.