Abstract Comparing one’s appearance to other people’s and believing in an ideal body shape can negatively impact an individual. The probability of developing ED in individuals with high body dissatisfaction is higher than in the general population, leading to long-term emotional and metabolic damage. Populational studies on the prevalence of ED in Brazil are scarce in the literature. The research was carried out through the Google Forms website and evaluated risk of eating disorders through the Eating Attitude Test, degree of body dissatisfaction in the sample through the Body Shape Questionnaire and the Internet Addiction Test was used to evaluate time spent on the internet. The results showed that 84.5% of the sample were female and 62.3% of the individuals had eutrophic by the Body Mass Index. About 40.2% of the population studied had abnormal attitudes towards food, indicating a possible risk of developing ED, and 62.5% of the sample did not show body dissatisfaction. Regarding internet use, 10.8% had problematic internet use. The presence of risky eating attitudes was more prevalent in participants dissatisfied with their bodies. In addition, participants with problematic internet use had a higher risk for EDs. ones one s peoples people individual longterm long term damage literature 845 84 5 84.5 623 62 3 62.3 Index 402 40 2 40.2 food 625 62.5 108 10 8 10.8 bodies addition EDs 84. 6 62. 4 40. 1 10.

Objective: To evaluate the factor structure, reliability, and validity of the Brazilian version of the Suicide Crisis Inventory-2 (SCI-2) among Brazilian adults. Methods: The SCI-2 was cross-culturally adapted into Portuguese and administered to 2,265 Brazilian participants. Confirmatory factor analysis (CFA) was used to assess factor structure, internal consistency, convergent validity, and criterion validity by using measures such as suicidal narratives, stressful life events, suicidal ideation, and suicide attempts. Results: The revised one-factor model of the SCI-2 demonstrated an adequate, although not optimal, model fit (χ2[1539] = 31,442.79, p < 0.001, comparative fit index [CFI] = 0.99, Tucker-Lewis index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.09, standardized root mean residual [SRMR] = 0.05). The revised five-factor model, on the other hand, demonstrated good fit (χ2[1529] = 14,174.86, p < 0.001, CFI = 1.00, TLI = 1.00, RMSEA = 0.06, SRMR = 0.04). Comparison of these two models indicated that the five-factor model had a better fit than the one-factor model. Both the total and subscale scores of the SCI-2 showed strong internal consistency and good convergent and criterion validity in relation to stressful life events, suicidal narratives (excluding the goal disengagement subscale), suicidal ideation, and suicide attempts. Conclusion: Our findings suggest that the Brazilian version of the SCI-2 is a valid tool for assessing symptoms of suicidal crisis syndrome. Objective structure reliability Inventory2 Inventory 2 Inventory- SCI2 SCI (SCI-2 adults Methods SCI- crossculturally cross culturally 2265 265 2,26 participants CFA (CFA events ideation attempts Results onefactor one adequate optimal χ21539 χ χ2 1539 (χ2[1539 3144279 31 442 79 31,442.79 0001 0 001 0.001 [CFI 099 99 0.99 TuckerLewis Tucker Lewis [TLI [RMSEA 009 09 0.09 [SRMR 0.05. 005 0.05 . 05 0.05) fivefactor five hand χ21529 1529 (χ2[1529 1417486 14 174 86 14,174.86 100 1 00 1.00 006 06 0.06 0.04. 004 0.04 04 0.04) excluding subscale, , subscale) Conclusion syndrome (SCI- 226 26 2,2 χ2153 153 (χ2[153 314427 3 44 7 31,442.7 000 0.00 9 0.9 0.0 χ2152 152 (χ2[152 141748 17 8 14,174.8 10 1.0 (SCI 22 2, χ215 15 (χ2[15 31442 4 31,442. 0. 14174 14,174. 1. χ21 (χ2[1 3144 31,442 1417 14,174 (χ2[ 314 31,44 141 14,17 (χ2 31,4 14,1 (χ 31, 14,

Abstract This article aims to examine differences in suicidal narrative and suicide crisis syndrome symptoms, and suicidal ideation among those who maintained, lost, and gained employment or student status during the COVID-19 pandemic. It is a cross-sectional study based on an online and anonymous self-report questionnaire. Participants were recruited through social media platforms between November 2020 and October 2021. Changes in occupational status were assessed in 2,259 individuals. The sample was divided into four groups according to work (full-time/part-time) and study status (1) maintained, (2) lost, (3) gained, and (4) unemployed. Suicide outcomes were investigated by the Suicidal Narrative Inventory, Suicide Crisis Inventory, and Columbia - Suicide Severity Rating Scale Screener version. Changes in occupational status influenced symptoms of the suicide crisis syndrome and suicidal narrative, but not suicidal ideation. Those who maintained their work, such as full-time/part-time scored lower on the total scores of the Suicidal Narrative Inventory and Suicide Crisis Inventory-2 compared to those who lost their employed status and unemployed. Our findings suggest that it is appropriate to consider changes in employed status as a mental health risk factor during pandemics.

Resumo O objetivo do artigo é examinar diferenças nos sintomas da narrativa suicida e da síndrome de crise de suicídio e ideação suicida entre aqueles que mantiveram, perderam e ganharam emprego ou status educacional durante a pandemia de COVID-19. Trata-se de um estudo transversal baseado em um questionário online. Os indivíduos foram recrutados por meio de plataformas de mídia social entre novembro de 2020 e outubro de 2021. As mudanças no status ocupacional foram avaliadas em 2.259 indivíduos. A amostra foi dividida em grupos de acordo com as mudanças do status ocupacional: (1) aqueles que mantiveram, (2) aqueles que perderam, (3) aqueles que ganharam e (4) desempregados. Desfechos suicidas foram avaliados através do Inventário da Narrativa Suicida, Inventário da Crise Suicida e Columbia - Escala de Classificação da Gravidade do Suicídio. Mudanças no status ocupacional influenciaram sintomas da síndrome de crise de suicídio e narrativa suicida, mas não a ideação suicida. Aqueles que mantiveram seu emprego apresentaram menos sintomas de narrativa suicida e síndrome de crise de suicídio, comparados aos que perderam o emprego e aos desempregados. Esses achados sugerem que é apropriado considerar mudanças no status ocupacional como fator de risco para saúde mental durante pandemias.

Resumo O objetivo do artigo é examinar diferenças nos sintomas da narrativa suicida e da síndrome de crise de suicídio e ideação suicida entre aqueles que mantiveram, perderam e ganharam emprego ou status educacional durante a pandemia de COVID-19. Trata-se de um estudo transversal baseado em um questionário online. Os indivíduos foram recrutados por meio de plataformas de mídia social entre novembro de 2020 e outubro de 2021. As mudanças no status ocupacional foram avaliadas em 2.259 indivíduos. A amostra foi dividida em grupos de acordo com as mudanças do status ocupacional: (1) aqueles que mantiveram, (2) aqueles que perderam, (3) aqueles que ganharam e (4) desempregados. Desfechos suicidas foram avaliados através do Inventário da Narrativa Suicida, Inventário da Crise Suicida e Columbia - Escala de Classificação da Gravidade do Suicídio. Mudanças no status ocupacional influenciaram sintomas da síndrome de crise de suicídio e narrativa suicida, mas não a ideação suicida. Aqueles que mantiveram seu emprego apresentaram menos sintomas de narrativa suicida e síndrome de crise de suicídio, comparados aos que perderam o emprego e aos desempregados. Esses achados sugerem que é apropriado considerar mudanças no status ocupacional como fator de risco para saúde mental durante pandemias. COVID19. COVID19 COVID 19. 19 COVID-19 Tratase Trata se online 202 2021 2259 2 259 2.25 1 (1 (2 3 (3 4 (4 desempregados Suicídio pandemias COVID1 COVID-1 20 225 25 2.2 ( COVID- 22 2.

Abstract This article aims to examine differences in suicidal narrative and suicide crisis syndrome symptoms, and suicidal ideation among those who maintained, lost, and gained employment or student status during the COVID-19 pandemic. It is a cross-sectional study based on an online and anonymous self-report questionnaire. Participants were recruited through social media platforms between November 2020 and October 2021. Changes in occupational status were assessed in 2,259 individuals. The sample was divided into four groups according to work (full-time/part-time) and study status (1) maintained, (2) lost, (3) gained, and (4) unemployed. Suicide outcomes were investigated by the Suicidal Narrative Inventory, Suicide Crisis Inventory, and Columbia - Suicide Severity Rating Scale Screener version. Changes in occupational status influenced symptoms of the suicide crisis syndrome and suicidal narrative, but not suicidal ideation. Those who maintained their work, such as full-time/part-time scored lower on the total scores of the Suicidal Narrative Inventory and Suicide Crisis Inventory-2 compared to those who lost their employed status and unemployed. Our findings suggest that it is appropriate to consider changes in employed status as a mental health risk factor during pandemics. COVID19 COVID 19 COVID-1 pandemic crosssectional cross sectional selfreport self report questionnaire 202 2021 2259 2 259 2,25 individuals fulltime/parttime fulltimeparttime full time/part time part (full-time/part-time 1 (1 (2 3 (3 4 (4 unemployed version Inventory2 Inventory- pandemics COVID1 COVID- 20 225 25 2,2 fulltime parttime timepart ( 22 2,

Objective: To evaluate the factor structure, reliability, and validity of the Brazilian version of the Suicide Crisis Inventory-2 (SCI-2) among Brazilian adults. Methods: The SCI-2 was cross-culturally adapted into Portuguese and administered to 2,265 Brazilian participants. Confirmatory factor analysis (CFA) was used to assess factor structure, internal consistency, convergent validity, and criterion validity by using measures such as suicidal narratives, stressful life events, suicidal ideation, and suicide attempts. Results: The revised one-factor model of the SCI-2 demonstrated an adequate, although not optimal, model fit (χ2[1539] = 31,442.79, p < 0.001, comparative fit index [CFI] = 0.99, Tucker-Lewis index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.09, standardized root mean residual [SRMR] = 0.05). The revised five-factor model, on the other hand, demonstrated good fit (χ2[1529] = 14,174.86, p < 0.001, CFI = 1.00, TLI = 1.00, RMSEA = 0.06, SRMR = 0.04). Comparison of these two models indicated that the five-factor model had a better fit than the one-factor model. Both the total and subscale scores of the SCI-2 showed strong internal consistency and good convergent and criterion validity in relation to stressful life events, suicidal narratives (excluding the goal disengagement subscale), suicidal ideation, and suicide attempts. Conclusion: Our findings suggest that the Brazilian version of the SCI-2 is a valid tool for assessing symptoms of suicidal crisis syndrome. Objective structure reliability Inventory2 Inventory 2 Inventory- SCI2 SCI (SCI-2 adults Methods SCI- crossculturally cross culturally 2265 265 2,26 participants CFA (CFA events ideation attempts Results onefactor one adequate optimal χ21539 χ χ2 1539 (χ2[1539 3144279 31 442 79 31,442.79 0001 0 001 0.001 [CFI 099 99 0.99 TuckerLewis Tucker Lewis [TLI [RMSEA 009 09 0.09 [SRMR 0.05. 005 0.05 . 05 0.05) fivefactor five hand χ21529 1529 (χ2[1529 1417486 14 174 86 14,174.86 100 1 00 1.00 006 06 0.06 0.04. 004 0.04 04 0.04) excluding subscale, , subscale) Conclusion syndrome (SCI- 226 26 2,2 χ2153 153 (χ2[153 314427 3 44 7 31,442.7 000 0.00 9 0.9 0.0 χ2152 152 (χ2[152 141748 17 8 14,174.8 10 1.0 (SCI 22 2, χ215 15 (χ2[15 31442 4 31,442. 0. 14174 14,174. 1. χ21 (χ2[1 3144 31,442 1417 14,174 (χ2[ 314 31,44 141 14,17 (χ2 31,4 14,1 (χ 31, 14,

Objectives: The kynurenine (KYN) pathway has been attracting attention as a relevant pathway in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We conducted a systematic review and meta-analysis of studies examining KYN pathway metabolites from cerebrospinal fluid (CSF) samples in SZ, BD, and MDD. Methods: The PubMed and Scopus databases were systematically searched to identify peer-reviewed case-control studies published until April 2022 that assessed KYN metabolites, namely, tryptophan (TRP), KYN, kynurenic acid (KA), quinolinic acid (QA), and 3-hydroxykynurenine (3-HK), in subjects with SZ, BD, or MDD compared with healthy controls (HC). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The random effects model method was selected for comparison of standardized mean differences (SMD) between two groups. Results: Twenty-three articles met the inclusion criteria (k = 8, k = 8, k = 11, for SZ, BD, and MDD, respectively). In SZ, KA levels were increased (SMD = 2.64, confidence interval [CI] = 1.16 to 4.13, p = 0.0005, I2 = 96%, k = 6, n=384). TRP (k = 5) and KYN (k = 4) did not differ significantly. In BD, TRP levels (k = 7) did not differ significantly. The level of KA was increased in MDD (k = 2), but the small number of studies precluded evaluation of statistical significance. Finally, in MDD, although some studies tended to show an increased level of KYN in those with remission vs. decreased levels in those with current depression, no significant difference was found in any KYN metabolite levels. Similarly, an increased level of QA was found, but the number of studies (k = 2) was small. Conclusion: KA, which has possibly neuroprotective effects, is increased in SZ. QA, which has neurotoxic effects, may be increased in MDD. There were no alterations in BD. Alterations in the KYN pathway may occur based on population characteristics and mood states. Future studies should explore the utility of these metabolites as biomarkers. Objectives (KYN SZ , (SZ) BD (BD) . (MDD) metaanalysis meta analysis CSF (CSF Methods peerreviewed peer reviewed casecontrol case control 202 namely TRP, (TRP) (KA) (QA) 3hydroxykynurenine hydroxykynurenine 3 3HK, 3HK HK (3-HK) HC. HC (HC) MetaAnalyses Meta Analyses PRISMA (PRISMA followed SMD groups Results Twentythree Twenty three 8 11 respectively. respectively respectively) 264 2 64 2.64 CI [CI 116 1 16 1.1 413 4 13 4.13 00005 0 0005 0.0005 I 96 96% 6 n=384. n384 n n=384 384 n=384) 5 significantly 7 2, significance Finally vs depression Similarly Conclusion states biomarkers (SZ (BD (MDD 20 (TRP (KA (QA (3-HK (HC 26 2.6 1. 41 4.1 0000 000 0.000 9 n38 n=38 38 2. 4. 00 0.00 n3 n=3 0.0 n= 0.

Crisis hotlines are direct communication systems, usually telephone-based, set up to prevent suicide. However, few studies have evaluated their effectiveness. The present study aims to perform a systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, of the effectiveness of interventions through direct communication systems to reduce the number of suicides or suicide attempts. We searched the MEDLINE, Cochrane, SciELO, and ClinicaTrials.gov databases, and used the 2011 Oxford Centre for Evidence-Based Medicine Levels of Evidence classification. The literature search yielded 267 studies, of which 35 fulfilled the selection criteria. Although significant heterogeneity was found among studies, there is evidence that direct telephone interventions are effective when included in broader preventive protocols and provided by trained staff. Despite the limitations, which included heterogeneity of samples, designs, and outcome measures, we were able to design a protocol for the use of remote services to prevent suicide and suicide attempts. A hotline or similar system could be an effective intervention for broader suicide prevention programs. However, further research is necessary to specify which protocol components are key to enhance effectiveness. Systematic review registry number: PROSPERO CRD42020206517 telephonebased, telephonebased based, based telephone-based However MetaAnalyses Meta Analyses PRISMA (PRISMA framework attempts MEDLINE Cochrane SciELO ClinicaTrialsgov ClinicaTrials gov databases 201 EvidenceBased Based classification 26 3 criteria staff limitations samples designs measures programs CRD CRD4202020651 20 2 CRD420202065 CRD42020206 CRD4202020 CRD420202 CRD42020 CRD4202 CRD420 CRD42 CRD4

Objective: Changes in the kynurenine pathway are recognized in psychiatric disorders, but their role in Alzheimer’s disease (AD) is less clear. We aimed to conduct a systematic review and meta-analysis to determine whether tryptophan and kynurenine pathway metabolites are altered in AD. Methods: We performed a systematic review and random-effects meta-analyses. Inclusion criteria were studies that compared AD and cognitively normal (CN) groups and assessed tryptophan or kynurenine pathway metabolites in cerebrospinal fluid or peripheral blood. Results: Twenty-two studies with a total of 1,356 participants (664 with AD and 692 CN individuals) were included. Tryptophan was decreased only in peripheral blood. The kynurenine-to-tryptophan ratio was only increased in peripheral blood of the AD group. 3-Hydroxykynurenine was decreased only in cerebrospinal fluid and showed higher variability in the CN group than the AD group. Kynurenic acid was increased in cerebrospinal fluid and decreased in peripheral blood. Finally, there were no changes in kynurenine and quinolinic acid between the groups. Conclusions: Our results suggested a shift toward the kynurenine pathway in both the brain and in the periphery, as well as a shift towards increased kynurenic acid production in the brain but decreased production in peripheral blood. In addition, our analysis indicated dissociation between the central and peripheral levels, as well as between plasma and serum for some of these metabolites. Finally, changes in the kynurenine pathway are suggested to be a core component of AD. More studies are warranted to verify and consolidate our results. Objective disorders Alzheimers Alzheimer s (AD clear metaanalysis meta Methods randomeffects random effects metaanalyses. metaanalyses analyses. analyses meta-analyses (CN Results Twentytwo Twenty two 1356 1 356 1,35 664 (66 69 individuals included kynureninetotryptophan 3Hydroxykynurenine Hydroxykynurenine 3 Finally Conclusions periphery addition levels 135 35 1,3 66 (6 6 13 1, (

Resumen El objetivo de este trabajo fue evaluar la vulnerabilidad social, en función de las características de la población, como medio para indicar los posibles espacios intraurbanos con mayores posibilidades de dispersión y contagio por COVID-19. Sobre la base de variables que explican las características sociales y aumentan la vulnerabilidad de los individuos, se seleccionó la información del IBGE, se trató mediante análisis factorial y se cartografió, de acuerdo con la adaptación de la metodología desarrollada por el Centro de Estudios Sociales de Coimbra. La escala de cobertura elegida fue la de los sectores censales de tres municipios del estado de Rio Grande do Sul/Brasil. El análisis dio como resultado 21 variables que per-miten clasificar cinco dimensiones de la vulnerabilidad de las po-blaciones, indicando los lugares donde las acciones para prevenir el contagio deben ser más incisivas, dadas las características de la población, y se evidenció la vulnerabilidad de las periferias urbanas. La agrupación de la información mostró dimensiones sociales que denotan aspectos auxiliares para la comprensión del territorio y la vulnerabilidad social a escala local. La metodología demostrada puede adoptarse fácilmente en diferentes escalas y regiones del Brasil, y también en otros países. Este estudio permitirá adoptar decisiones encaminadas a evitar el contagio y subvencionar con información la elaboración de planes para la reanudación gradual de las actividades económicas y sociales.

Abstract This work aimed to evaluate social vulnerability based on population characteristics as a means to indicate the possible intra-ur-ban spaces with greater chances of dispersion and contagion by COVID-19. Based on variables that explain social characteristics and increase the vulnerability of individuals, information from IBGE was selected, treated by factor analysis and mapped, according to the adaptation of the methodology developed by the Centre for Social Studies in Coimbra. The scale of coverage chosen was that of census sectors, from three municipalities in the state of Rio Grande do Sul/Brazil. The analysis resulted in 21 variables that make it possible to classify five dimensions of the vulnerability of the populations, indicating the places where actions to prevent contagion should be more incisive, given the population characteristics, and the vulnerability of urban peripheries was evidenced. The grouping of information expressed social dimensions that denote aspects auxiliary to understanding the territory and social vulnerability on a local scale. The methodology demonstrated can be easily adopted in different scales and regions of Brazil, and also in other countries. This study will make it possible to make decisions aimed at avoiding contagion, and to subsidize with information the elaboration of plans for the gradual resumption of economic and social activities.

Résumé Ce travail visait à évaluer la vulnérabilité sociale sur la base des caractéristiques de la population afin d'indiquer les espaces intra-ur-bains possibles avec de plus grandes chances de dispersion et de contagion par COVID-19. Sur la base de variables qui expliquent les caractéristiques sociales et augmentent la vulnérabilité des individus, les informations de l'IBGE ont été sélectionnées, traitées par analyse factorielle et cartographiées, selon l'adaptation de la méthodologie développée par le Centre d'études sociales de Coimbra. L'échelle de couverture choisie a été celle des secteurs de recensement, de trois municipalités de l'État du Rio Grande do Sul/Brésil. L'analyse a donné lieu à 21 variables qui permettent de classer cinq dimensions de la vulnérabilité des populations, indiquant les endroits où les actions de prévention de la contagion devraient être plus incisives, compte tenu des caractéristiques de la population, et la vulnérabilité des périphéries urbaines a été mise en évidence. Le regroupement des informations exprime des dimensions sociales qui dénotent des aspects auxiliaires à la compréhension du territoire et de la vulnérabilité sociale à l'échelle locale. La méthodologie démontrée peut être facilement adoptée à différentes échelles et régions du Brésil, ainsi que dans d'autres pays. Cette étude permettra de prendre des décisions visant à éviter la contagion, et de subventionner par l'information l'élaboration de plans de reprise progressive des activités économiques et sociales.

Resumo Este trabalho teve por objetivo avaliar a vulnerabilidade social a partir de características da população como meio de indicar os possíveis espaços intraurbanos com maiores chances de dispersão e contágio por COVID-19. A partir de variáveis que explicitam características sociais e ampliam a vulnerabilidade dos indivíduos, foram selecionadas informações do IBGE, tratadas por análise fatorial e mapeadas, conforme adaptação da metodologia desenvolvida pelo Centro de Estudos Sociais, em Coimbra. A escala de abrangência escolhida foi a de setores censitários, a partir de três municípios do estado do Rio Grande do Sul/Brasil. A análise resultou em 21 variáveis que possibilitam classificar cinco dimensões da vulnerabilidade das populações, indicando os locais onde ações de prevenção ao contágio devem ser mais incisivas, dadas as características populacionais, e evidenciou-se a vulnerabilização de periferias urbanas. O agrupamento de informações expressou dimensões sociais que denotam aspectos auxiliares na compreensão do território e da vulnerabilidade social em escala local. A metodologia demonstrada pode ser facilmente adotada em diferentes escalas e regiões do Brasil, e também em outros países. Esse estudo possibilitará a tomada de decisões visando evitar o contágio, e subsidiar com informações a elaboração de planos para a retomada gradual das atividades econômicas e social.

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Treatment-resistant bipolar depression (TRBD) has been reported in about one-quarter of patients with bipolar disorders, and few interventions have shown clear and established effectiveness. We conducted a narrative review of the published medical literature to identify papers discussing treatment-resistant depression concepts and novel interventions for bipolar depression that focus on TRBD. We searched for potentially relevant English-language articles published in the last decade. Selected articles (based on the title and abstract) were retrieved for a more detailed evaluation. A number of promising new interventions, both pharmacological and non-pharmacological, are being investigated for TRBD treatment, including ketamine, lurasidone, D-cycloserine, pioglitazone, N-acetylcysteine, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, cyclooxygenase 2 inhibitors, magnetic seizure therapy, intermittent theta-burst stimulation, deep transcranial magnetic stimulation, vagus nerve stimulation therapy, and deep brain stimulation. Although there is no consensus about the concept of TRBD, better clarification of the neurobiology associated with treatment non-response could help identify novel strategies. More research is warranted, mainly focusing on personalizing current treatments to optimize response and remission rates.