Objective: The Patient Health Questionnaire-9 (PHQ-9) is a widely used self-report measure of depression whose psychometric properties were found to be merely acceptable. Insufficient attention has been devoted to its clinimetric validity, while its clinical utility is still debated, particularly for assessing depression severity. This is the first study to test the PHQ-9 construct validity and clinical utility based on clinimetric principles. Methods: An online survey of 3,398 participants was conducted. Item response theory models (Rasch and Mokken analyses) were used to assess the PHQ-9 validity and determine its clinical utility. Results: Fit to the Rasch model was achieved after adjusting the sample size. Items 2, 4, 6, and 9 over-discriminated, while items 1, 5, and 7 under-discriminated. Local dependency between items 2 and 6 was indicated. The PHQ-9 was not unidimensional. A Loevinger’s coefficient of 0.49 was found, indicating an acceptable level of scalability. Conclusion: The PHQ-9 is an instrument with potential clinical utility as an overall index of depression, mainly for screening purposes. Substantial revision, particularly in the wording of over- and under-discriminating items, is needed. Objective Questionnaire9 Questionnaire Questionnaire- PHQ9 PHQ (PHQ-9 selfreport self report debated severity PHQ- principles Methods 3398 3 398 3,39 conducted analyses Results size 4 overdiscriminated, overdiscriminated over discriminated, discriminated over-discriminated 1 5 underdiscriminated. underdiscriminated under discriminated. under-discriminated indicated unidimensional Loevingers Loevinger s 049 0 49 0.4 scalability Conclusion purposes revision underdiscriminating discriminating needed (PHQ- 339 39 3,3 04 0. (PHQ 33 3,

Objective: To determine whether the stigma associated with schizophrenia has also been directed towards people at ultra-high risk of psychosis (UHR), the present review aimed to synthetize the literature to update and extend our understanding of this topic. Methods: A systematic review compliant with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in the PubMed, EMBASE, Cochrane, and Web of Science databases for articles published until April 30, 2023, using a combination of search terms describing at-risk mental states for psychosis, stigma, and related terms. Results: Thirty-eight studies were included. Twenty-nine addressed individuals with UHR directly, and nine conducted interviews with non-patients regarding UHR. A total of 2,560 individuals with UHR were assessed, with a mean sample size of 88.3 participants. Most were quantitative non-randomized/observational studies with young adults, 71.4% used the Structured Interview for Psychosis-Risk Syndromes, and 25% used the Comprehensive Assessment of At-Risk Mental States. Overall, the studies mainly involved patients of UHR clinics from high-income Western countries. The described stigma can be grouped into five forms, the most frequently explored of which was perceived public stigma, followed by public stigma, self-stigma/internalized stigma, stigma stress, and associative stigma. Quantitative nonrandomized studies predominated: only one was an interventional study. Most of the results confirmed the presence of stigma toward individuals with UHR. Conclusion: Despite the knowledge gaps and scarcity of research on UHR-related stigma, the results suggest that stigma toward people with UHR exists and that it is already present at early stages of psychosis. Registration number: PROSPERO CRD42022332037. Objective ultrahigh ultra high UHR, , (UHR) topic Methods MetaAnalyses Meta Analyses PubMed EMBASE Cochrane 30 2023 atrisk Results Thirtyeight Thirty eight included Twentynine Twenty directly nonpatients non 2560 2 560 2,56 assessed 883 88 3 88. participants nonrandomized/observational nonrandomizedobservational randomized/observational randomized observational adults 714 71 4 71.4 PsychosisRisk Psychosis Risk Syndromes 25 AtRisk At States Overall highincome income countries forms selfstigma/internalized selfstigmainternalized self stigma/internalized internalized stress predominated study Conclusion UHRrelated number CRD42022332037 CRD (UHR 202 256 56 2,5 8 randomizedobservational 7 71. selfstigma stigmainternalized CRD4202233203 20 5 2, CRD420223320 CRD42022332 CRD4202233 CRD420223 CRD42022 CRD4202 CRD420 CRD42 CRD4

Objective: The advancement of neuroimaging and genetic research has revealed the presence of morphological abnormalities and numerous risk genes, along with their associations. We aimed to estimate magnetic resonance imaging-derived cortical thickness across multiple brain regions. Methods: The cortical thickness of 129 schizophrenia patients, 42 of their unaffected siblings, and 112 healthy controls was measured and the candidate genes were sequenced. Comparisons were made of cortical thickness (including 68 regions of the Desikan-Killiany Atlas) and genetic variants (in 108 risk genes for schizophrenia) among the three groups, and correlation analyses were performed regarding cortical thickness, clinical symptoms, cognitive tests (such as the N-back task and the logical memory test), and genetic variants. Results: Schizophrenia patients had significantly thinner bilateral frontal, temporal, and parietal gyri than healthy controls and unaffected siblings. Association analyses in target genes showed that four single nucleotide variants (SNVs) were significantly associated with schizophrenia, including thioredoxin-related transmembrane protein 2-catenin, cadherin-associated protein, delta 1 (SNV20673) (positive false discovery rate [PFDR] = 0.008) and centromere protein M (rs35542507, rs41277477, rs73165153) (PFDR = 0.030). Additionally, cortical thickness in the right pars triangularis was lower in carriers of the SNV20673 variant than in non-carriers (PFDR = 0.048). Finally, a positive correlation was found between right pars triangularis cortical thickness and logical memory in schizophrenia patients (r = 0.199, p = 0.032). Conclusions: This study identified regional morphological abnormalities in schizophrenia, including the right homologue of Broca’s area, which was associated with a risk variant that affected delta-1 catenin and logical memory. These findings suggest a potential association between candidate gene loci, cortical thickness, and schizophrenia. Objective associations imagingderived imaging derived Methods 12 4 siblings 11 sequenced 6 DesikanKilliany Desikan Killiany Atlas 10 groups symptoms such Nback N back test, test , test) Results frontal temporal SNVs (SNVs thioredoxinrelated thioredoxin related 2catenin, 2catenin 2 catenin, 2-catenin cadherinassociated cadherin SNV (SNV20673 PFDR [PFDR 0.008 0008 0 008 rs35542507, rs35542507 rs (rs35542507 rs41277477 rs73165153 0.030. 0030 0.030 . 030 0.030) Additionally SNV2067 noncarriers non 0.048. 0048 0.048 048 0.048) Finally r 0199 199 0.199 0.032. 0032 0.032 032 0.032) Conclusions Brocas Broca s area delta1 delta- loci (SNV2067 0.00 000 00 rs3554250 (rs3554250 rs4127747 rs7316515 003 0.03 03 SNV206 004 0.04 04 019 19 0.19 (SNV206 0.0 rs355425 (rs355425 rs412774 rs731651 SNV20 01 0.1 (SNV20 0. rs35542 (rs35542 rs41277 rs73165 SNV2 (SNV2 rs3554 (rs3554 rs4127 rs7316 (SNV rs355 (rs355 rs412 rs731 rs35 (rs35 rs41 rs73 rs3 (rs3 rs4 rs7 (rs

Objective: To evaluate the prevalence of attention-deficit/hyperactivity disorder (ADHD), comorbidity rates with disruptive behavior disorders and main negative outcomes in primary school students in Nampula, Mozambique. Methods: We selected a random sample of 748 students for ADHD screening from a population of around 43,000 primary school students. The Swanson, Nolan, and Pelham Rating Scale version IV was applied to both parents and teachers. All students who screened positive (n=76) and a propensity score-matched random subset of students who screened negative (n=76) were assessed by a child psychiatrist. Results: The prevalence of ADHD was estimated at 13.4% (95%CI 11.5-19.2), and 30.6% of those with ADHD presented comorbid disruptive behavior disorders. Students with ADHD (n=36) had significantly higher rates of both substance use (alcohol, marijuana) (p < 0.001), and school failures than controls (n=96; p < 0.001). Comorbidity between ADHD and disruptive behavior disorders increased the chance of substance use (p < 0.001). Secondary analyses with more restrictive ADHD diagnostic criteria revealed a lower prevalence rate (6.7%; 95%CI 5.2-12.9) with similar patterns of associated factors and negative outcomes. Conclusion: Our findings demonstrated that ADHD is a prevalent mental disorder in Mozambique, and it is associated with similar comorbid profiles, predisposing factors, and negative outcomes, as in other cultures. Objective attentiondeficit/hyperactivity attentiondeficithyperactivity attention deficit/hyperactivity deficit hyperactivity ADHD, , (ADHD) Nampula Mozambique Methods 74 43000 43 000 43,00 Swanson Nolan teachers n=76 n76 n 76 (n=76 scorematched score matched psychiatrist Results 134 13 4 13.4 95CI CI 95 11.519.2, 115192 11.5 19.2 11 5 19 2 11.5-19.2) 306 30 6 30.6 n=36 n36 36 (n=36 alcohol, alcohol (alcohol marijuana 0.001, 0001 0.001 0 001 0.001) n=96 n96 96 (n=96 0.001. . 6.7% 67 7 (6.7% 5.212.9 52129 5.2 12.9 12 9 5.2-12.9 Conclusion profiles cultures attentiondeficit deficithyperactivity (ADHD 4300 00 43,0 n=7 n7 (n=7 1 13. 519 11.519.2 11519 115 11. 192 19. 11.5-19.2 3 30. n=3 n3 (n=3 0.00 n=9 n9 (n=9 6.7 (6.7 212 5.212. 5212 52 5. 129 12. 5.2-12. 430 43, n= (n= 51 11.519. 1151 11.5-19. 0.0 6. (6. 21 5.212 521 5.2-12 (n 11.519 11.5-19 0. (6 5.21 5.2-1 11.51 11.5-1 ( 5.2- 11.5-

Objectives: To estimate the prevalence of antidepressant use in Brazil. Methods: We conducted a systematic review with searches in MEDLINE, Embase, Scopus, LILACS, and SciELO up to May 2023. Two researchers independently selected studies, extracted data, and assessed the methodological quality. We pooled the prevalence of antidepressant use using meta-analyses of proportions (Freeman-Tukey transformation) and estimated heterogeneity by the I2 statistic. OR meta-analyses of antidepressant use by sex were calculated (men as reference) and between-study variation was explored by meta-regressions. Results: Out of 3,299 records retrieved, 23 studies published in 28 reports were included, with a total of 75,061 participants. The overall prevalence of antidepressant use was 4.0% (95%CI 2.7-5.6%; I2 = 98.5%). Use of antidepressants in the previous 3 days was higher in women (12.0%; 95%CI 9.5-15.1%; I2 = 0%) than men (4.6%; 95%CI 3.1-6.8%; I2 = 0%) (p < 0.001; OR = 2.82; 95%CI 1.72-4.62). Gender differences were particularly higher for antidepressant use in the previous year (women: 2.3%; 95%CI 1.6-3.1; I2 = 37.6% vs. men: 0.5%; 95%CI 0.2-1.0%; I2 = 0%, p < 0.001; OR = 4.18; 95%CI 2.10-8.30). Between-study variation in the overall prevalence of antidepressant use significantly increased with mean participant age (p = 0.035; residual I2 = 0%; regression coefficient = 0.003). Conclusion: Four out of every 100 Brazilians used antidepressants in this 3-decade assessment. Use increased with age and was more prevalent in women compared to men. Registration number: PROSPERO CRD42022345332. Objectives Brazil Methods MEDLINE Embase Scopus LILACS 2023 data quality metaanalyses meta analyses FreemanTukey Freeman Tukey transformation I statistic reference betweenstudy between study metaregressions. metaregressions regressions. regressions meta-regressions Results 3299 299 3,29 retrieved 2 included 75061 75 061 75,06 participants 40 4 0 4.0 95CI CI 95 2.75.6% 2756 2.7 5.6% 7 5 6 2.7-5.6% 98.5%. 985 98.5% . 98 98.5%) 12.0% 120 12 (12.0% 9.515.1% 95151 9.5 15.1% 9 15 1 9.5-15.1% 0% 4.6% 46 (4.6% 3.16.8% 3168 3.1 6.8% 8 3.1-6.8% 0.001 0001 001 2.82 282 82 1.724.62. 172462 1.72 4.62 72 62 1.72-4.62) (women 2.3% 1.63.1 1631 1.6 1.6-3.1 376 37 37.6 vs 0.5% 05 0.21.0% 0210 0.2 1.0% 0.2-1.0% 4.18 418 18 2.108.30. 210830 2.10 8.30 10 30 2.10-8.30) Betweenstudy Between 0.035 0035 035 0.003. 0003 0.003 003 0.003) Conclusion 3decade decade assessment number CRD42022345332 CRD 202 329 29 3,2 7506 06 75,0 4. 2.75.6 275 27 2. 56 5.6 2.7-5.6 98.5 12.0 (12.0 515 9.515.1 9515 9. 151 15.1 9.5-15.1 4.6 (4.6 16 3.16.8 316 31 3. 68 6.8 3.1-6.8 0.00 000 00 2.8 724 1.724.62 17246 172 1.7 462 1.72-4.62 2.3 63 1.63. 163 1. 1.6-3. 37. 0.5 21 0.21.0 021 02 0. 1.0 0.2-1.0 4.1 41 108 2.108.30 21083 210 2.1 830 8.3 2.10-8.30 0.03 03 CRD4202234533 20 32 3, 750 75, 2.75. 5. 2.7-5. 98. 12. (12. 51 9.515. 951 15. 9.5-15. (4. 3.16. 6. 3.1-6. 0.0 1.724.6 1724 17 1.72-4.6 1.63 1.6-3 0.21. 0.2-1. 2.108.3 2108 83 8. 2.10-8.3 CRD420223453 2.75 2.7-5 (12 9.515 9.5-15 (4 3.16 3.1-6 1.724. 1.72-4. 1.6- 0.21 0.2-1 2.108. 2.10-8. CRD42022345 2.7- (1 9.51 9.5-1 ( 3.1- 1.724 1.72-4 0.2- 2.108 2.10-8 CRD4202234 9.5- 1.72- 2.10- CRD420223 CRD42022 CRD4202 CRD420 CRD42 CRD4

Objective: Evidence on the relationship between depression and clinical dimensions of schizophrenia remains limited. This cross-sectional study investigated the association between depression and Positive and Negative Syndrome Scale (PANSS) dimensions in people with schizophrenia spectrum disorders. Methods: Trained assessors administered the PANSS to measure symptoms of schizophrenia and the Calgary Depression Scale for Schizophrenia to measure depression. The association of depression with overall PANSS score and related dimensions was investigated in multiple logistic regression analyses. Results: We included 231 inpatients with schizophrenia spectrum disorders (mean age: 42.4 (SD: 12.9) years; men: 58.9%; mean overall PANSS score: 82.5 (SD: 20.1); drug-free or naïve: 39.3%), including 78 (33.8%) with clinically significant depressive symptoms. Depression was associated with higher overall (regression coefficient, SE: 0.029, 0.008; p < 0.001) and general psychopathology (regression coefficient, SE: 0.118, 0.023; p < 0.001) PANSS scores. We found an inverse relationship between depression and positive symptoms (regression coefficient, SE: -0.088, 0.028; p = 0.002). No association between depression and negative symptoms was found. Conclusion: Despite some limitations, our study shows that people affected by schizophrenia spectrum disorders with depression are likely to show more overall and general psychopathology symptoms but lower positive symptoms. Additional studies are needed to explore the generalizability of our findings. Objective limited crosssectional cross sectional (PANSS Methods analyses Results 23 age 424 42 4 42. SD (SD 12.9 129 12 9 years men 58.9% 589 58 825 82 5 82. 20.1 201 20 1 20.1) drugfree drug free naïve 39.3%, 393 39.3% , 39 3 39.3%) 7 33.8% 338 33 8 (33.8% coefficient SE 0029 0 029 0.029 0.008 0008 008 0.001 0001 001 0118 118 0.118 0.023 0023 023 scores 0.088, 0088 088 -0.088 0.028 0028 028 0.002. 0002 0.002 . 002 0.002) Conclusion limitations findings 2 12. 58.9 20. 39.3 33.8 (33.8 02 0.02 0.00 000 00 011 11 0.11 0.088 08 -0.08 58. 39. 33. (33. 0.0 01 0.1 0.08 -0.0 (33 0. -0. (3 -0 ( -

Objective: To ascertain whether sociodemographic and health-related characteristics known from previous research to have a substantive impact on recovery from depression modified the effect of a digital intervention designed to improve depressive symptoms (CONEMO). Methods: The CONEMO study consisted of two randomized controlled trials, one conducted in Lima, Peru, and one in São Paulo, Brazil. As a secondary trial plan analysis, mixed logistic regression was used to explore interactions between the treatment arm and subgroups of interest defined by characteristics measured before randomization – suicidal ideation, race/color, age, gender, income, type of mobile phone, alcohol misuse, tobacco use, and diabetes/hypertension – in both trials. We estimated interaction effects between the treatment group and these subgroup factors for the secondary outcomes using linear mixed regression models. Results: Increased effects of the CONEMO intervention on the primary outcome (reduction of at least 50% in depressive symptom scores at 3-month follow-up) were observed among older and wealthier participants in the Lima trial (p = 0.030 and p = 0.001, respectively). Conclusion: There was no evidence of such differential effects in São Paulo, and no evidence of impact of any other secondary outcomes in either trial. Clinical trial registration: NCT02846662 (São Paulo, Brazil – SP), NCT03026426 (Lima, Peru – LI). Funded by the U.S. National Institute of Mental Health (grant U19MH098780). Objective healthrelated health related CONEMO. . (CONEMO) Methods trials Paulo analysis ideation racecolor race color race/color age gender income phone misuse use diabeteshypertension diabetes hypertension models Results reduction 50 3month month 3 followup follow up follow-up 0030 0 030 0.03 0001 001 0.001 respectively. respectively respectively) Conclusion registration NCT NCT0284666 SP, SP , SP) NCT0302642 (Lima LI. LI LI) US U S U.S grant U19MH098780. U19MH098780 UMH MH U19MH098780) (CONEMO 5 003 03 0.0 000 00 0.00 NCT028466 NCT030264 U19MH09878 0. NCT02846 NCT03026 U19MH0987 NCT0284 NCT0302 U19MH098 NCT028 NCT030 U19MH09 NCT02 NCT03 U19MH0 NCT0 U19MH

Objectives: To study the impact of coronavirus disease 2019 on the routine of patients with obsessive-compulsive disorder (OCD) and changes in symptoms and suicidal-related behavior, mainly in those with cleaning symptoms. Methods: In this cross-sectional study, 58 patients completed an online self-report questionnaire that included the Obsessive-Compulsive Inventory-Revised, Coronavirus Stress and Traumatic Events Scale, Coronavirus Health Impact Survey, Beck Anxiety and Beck Depression inventories, and Suicide-Related Behaviors Questionnaire. Comparisons were made with another pre-pandemic sample (n=524) regarding the last three measures. Results: During the pandemic, the patients spent more days inside their homes (χ2 = 33.39, p = 0.007), changed their alcohol consumption patterns (χ2 = 87.6, p < 0.001), and increased social media usage (χ2 = 68.83, p < 0.001). Participants with cleaning symptoms did not significantly differ from the others in relation to stress, anxiety/depressive symptoms, or suicidal-related behaviors. Finally, our sample did not differ from an equivalent OCD sample assessed before the pandemic in terms of anxiety and depressive symptom severity or suicidal-related behaviors. Conclusion: Overall, patients with OCD showed no lifestyle changes associated with higher stress levels during the pandemic. Patients with and without cleaning symptoms and patients before and during the pandemic presented similar results. Objectives 201 obsessivecompulsive obsessive compulsive (OCD suicidalrelated suicidal related behavior Methods crosssectional cross sectional 5 selfreport self report ObsessiveCompulsive Obsessive Compulsive InventoryRevised, InventoryRevised Inventory Revised, Revised Inventory-Revised Scale Survey inventories SuicideRelated Suicide Related Questionnaire prepandemic pre n=524 n524 n 524 (n=524 measures Results χ2 χ (χ 3339 33 39 33.39 0.007, 0007 0.007 , 0 007 0.007) 876 87 6 87.6 0.001, 0001 0.001 001 0.001) 6883 68 83 68.83 0.001. . anxietydepressive behaviors Finally Conclusion Overall results 20 n=52 n52 52 (n=52 333 3 33.3 000 0.00 00 8 87. 688 68.8 2 n=5 n5 (n=5 33. 0.0 68. n= (n= 0. (n

Objective: To investigate whether having a higher number of depressive symptoms is associated with negative self-rated health (SRH) even in the absence of illness. Methods: This is a secondary analysis of baseline data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), conducted in 2015-2016, using a national sample of 9,412 people aged 50 or over. SRH was dichotomized into poor or very poor and very good or excellent, good, or average. Depressive symptoms were assessed through the eight-item Center for Epidemiologic Studies Depression Scale (CES-D8). Sociodemographic variables, information about unhealthy behaviors, and the number of chronic conditions were also analyzed. Results: Having depressive symptoms was strongly associated with poor or very poor SRH both in the unadjusted and adjusted analyses. The magnitude of the association was reduced when the number of chronic illnesses was included in the multivariate analysis, along with the other sociodemographic variables and unhealthy behaviors (OR 1.35, 95%CI 1.31-1.39). Conclusion: Having depressive symptoms may contribute towards having a poorer perception of health, even in the absence of health conditions. SRH is a multidimensional construct that can accurately reflect a person’s state of general mental health. Objective selfrated self rated (SRH illness Methods ELSIBrazil, ELSIBrazil ELSI Brazil , (ELSI-Brazil) 20152016, 20152016 2015 2016, 2016 2015-2016 9412 9 412 9,41 5 over excellent average eightitem eight item CESD8. CESD8 CESD CES D8 . D (CES-D8) analyzed Results analyses OR 135 1 35 1.35 95CI CI 95 1.311.39. 131139 1.31 1.39 31 39 1.31-1.39) Conclusion persons person s (ELSI-Brazil 2015201 201 2015-201 941 41 9,4 (CES-D8 13 3 1.3 311 1.311.39 13113 131 139 1.31-1.39 201520 20 2015-20 94 4 9, (CES-D 1. 1.311.3 1311 1.31-1.3 20152 2 2015-2 1.311. 1.31-1. 2015- 1.311 1.31-1 1.31-

Objective: To adapt the Mind-Wandering Questionnaire (MWQ) for the Brazilian context and present evidence of validity based on its internal structure. Methods: A total of 2,682 Brazilian adults from different regions of the country took part in this study. Confirmatory factor analyses and multigroup confirmatory factor analyses (MGCFA) were performed to assess the factor structure of the MWQ. McDonald’s omega (ω) was generated to provide reliability indexes. Results: The analyses demonstrated an adequate factor structure for the MWQ adapted to the Brazilian context, corroborating the original article’s single-factor model and other adaptation studies. Furthermore, the results demonstrated the instrument’s reliability in a Brazilian population (ω = 0.88). Conclusion: The MWQ is thus an adequate, reliable, and quickly administered instrument for those whose aim is to measure deliberate and spontaneous MW in Brazil. Objective MindWandering Mind Wandering (MWQ Methods 2682 2 682 2,68 study MGCFA (MGCFA McDonalds McDonald s ω indexes Results articles article singlefactor single studies Furthermore instruments 0.88. 088 0.88 . 0 88 0.88) Conclusion reliable Brazil 268 68 2,6 08 0.8 8 26 6 2, 0.

Objectives: Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD. Methods: PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included. Results: Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-α], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region). Conclusion: This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged. Systematic review registration: PROSPERO CRD42021279246. Objectives DTI (DTI whitematter white matter (WM . (BD) however scarce bloodbased based Methods PubMed Embase searches Crosssectional Cross sectional by neuroimaging Results 3750 750 3,75 retrieved 2 interleukin8 interleukin 8 (interleukin- IL8, IL8 IL , [IL-8] TNFα, TNFα TNF α [TNF-α] insulinlike insulin like IGFBP3, IGFBP3 IGFBP [IGFBP-3]) natural NK, NK [NK]) lipid hydroperoxidase cholesterol triglycerides, triglycerides triglycerides) Kyn (Kyn 5hydroxyindoleacetic hydroxyindoleacetic 5 Kyna, Kyna [Kyna]) serotonintransporterlinked serotonin transporter linked region. region region) Conclusion encouraged registration CRD42021279246 CRD (BD 375 75 3,7 (interleukin [IL-8 [TNF-α [IGFBP-3] [NK] [Kyna] CRD4202127924 37 7 3, [IL- [IGFBP-3 [NK [Kyna CRD420212792 [IL [IGFBP- CRD42021279 [IGFBP CRD4202127 CRD420212 CRD42021 CRD4202 CRD420 CRD42 CRD4

Generalized anxiety disorder is a highly prevalent mental disorder. Previous data indicate that more than 18 million Brazilians suffer from this condition. Traditionally, generalized anxiety disorder has been considered a mild mental health disorder, despite its links to lower life expectancy, cardiovascular disease, and suicide. The aim of this article is to combine elements of systematic and critical reviews to produce a synthesis of the best evidence about generalized anxiety disorder treatment. Systematic reviews, meta-analyses, and randomized controlled trials were included. The descriptor used in the search was “generalized anxiety disorder,” which resulted in 4,860 articles and seven other studies, of which 59 were selected. Antidepressants and benzodiazepines were indicated, as was pregabalin, and atypical antipsychotics, such as quetiapine, have been studied. Individual cognitive behavior therapy (third wave) has proven effective. There is extensive literature on many effective treatments for generalized anxiety disorder. The present review summarizes the therapeutic possibilities, emphasizing those available in Brazil. Further studies are needed to compare other available medications, assess psychotherapies and new treatments in greater depth, as well as to assess the ideal duration of therapy. Registration number: PROSPERO CRD42021288323. 1 condition Traditionally expectancy disease suicide treatment metaanalyses, metaanalyses meta analyses, analyses meta-analyses included 4860 4 860 4,86 5 selected indicated pregabalin antipsychotics quetiapine studied third wave possibilities Brazil medications depth number CRD42021288323 CRD 486 86 4,8 CRD4202128832 48 8 4, CRD420212883 CRD42021288 CRD4202128 CRD420212 CRD42021 CRD4202 CRD420 CRD42 CRD4

Objective: To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) for attention deficit/hyperactivity disorder (ADHD). Methods: Randomized sham-controlled trials were identified in major databases from January 1990 to January 2023. The primary outcome was overall improvement in ADHD symptoms. Subgroup analysis focused on the efficacy of rTMS in different brain regions. Secondary outcomes were the association of rTMS with improvement in different ADHD symptoms. Outcomes were expressed as effect size based on standardized mean difference (SMD)(continuous data), and ORs with 95%CI (categorical data). Results: A meta-analysis of six randomized sham-controlled trials involving 169 participants demonstrated no difference in overall ADHD symptoms between those treated with rTMS and sham controls (SMD = -0.24, p = 0.17). Subgroup analysis revealed that rTMS was more efficacious than sham treatment when targeting the right prefrontal cortex (SMD = -0.49, p = 0.03) but not the left prefrontal cortex (SMD = 0.01, p = 0.67). rTMS treatment was correlated with greater improvement in inattention (SMD = -0.76, p = 0.0002), but not hyperactivity (p = 0.86), impulsivity (p = 0.41), or depression symptoms (p = 0.95). The apparently higher risk of dropout in the rTMS group than the sham control group was not statistically significant (OR = 1.65, p = 0.26). Conclusion: This review found that rTMS only had therapeutic efficacy for ADHD symptoms (particularly inattention) when targeting the right prefrontal cortex. Further large-scale randomized sham-controlled trials are required to verify our findings. Registration number: PROSPERO CRD42023393713. Objective (rTMS deficithyperactivity deficit ADHD. . (ADHD) Methods shamcontrolled controlled 199 2023 regions SMDcontinuous SMD continuous data, data , data) 95CI CI 95 categorical data. Results metaanalysis meta 16 0.24, 024 0 24 -0.24 0.17. 017 0.17 17 0.17) 0.49, 049 49 -0.49 0.03 003 03 001 01 0.01 0.67. 067 0.67 67 0.67) 0.76, 076 76 -0.76 0.0002, 00002 0.0002 0002 0.0002) 0.86, 086 0.86 86 0.86) 0.41, 041 0.41 41 0.41) 0.95. 095 0.95 0.95) OR 165 1 65 1.65 0.26. 026 0.26 26 0.26) Conclusion particularly largescale large scale findings number CRD42023393713 CRD (ADHD 19 202 9 0.24 02 2 -0.2 0.1 0.49 04 4 -0.4 0.0 00 06 0.6 6 0.76 07 7 -0.7 0000 0.000 000 08 0.8 8 0.4 09 0.9 1.6 0.2 CRD4202339371 20 -0. 0. 0.7 0.00 1. CRD420233937 -0 CRD42023393 - CRD4202339 CRD420233 CRD42023 CRD4202 CRD420 CRD42 CRD4