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BACKGROUND: Evidence indicates that physical activity reduces stress and promote a myriad of health-enhancing effects through anti-inflammatory mechanisms. However, it is unknown whether these mechanisms interfere in the association between psychosocial job stress and headache disorders. OBJECTIVE: To test whether physical activity and its interplay with the systemic inflammation biomarkers high-sensitivity C-reactive protein (hs-CRP) and acute phase glycoproteins (GlycA) would mediate the associations between job stress and headache disorders. METHODS: We cross-sectionally evaluated the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) regarding job stress (higher demand and lower control and support subscales), migraine and tension-type headache (ICHD-2 criteria), self-reported leisure-time physical activity, and plasma hs-CRP and GlycA levels. Conditional process analyses with a sequential mediation approach were employed to compute path coefficients and 95 % confidence intervals (CI) around the indirect effects of physical activity and biomarkers on the job stress-headache relationship. Separate models were adjusted for sex, age, and depression and anxiety. Further adjustments added BMI smoking status, and socioeconomic factors. RESULTS: In total, 7,644 people were included in the study. The 1-year prevalence of migraine and tension-type headache were 13.1 % and 49.4 %, respectively. In models adjusted for sex, age, anxiety, and depression, the association between job stress (lower job control) and migraine was mediated by physical activity [effect = -0.039 (95 %CI: -0.074, -0.010)] but not hs-CRP or GlycA. TTH was associated with higher job control and lower job demand, which was mediated by the inverse associations between physical activity and GlycA [Job Control: effect = 0.0005 (95 %CI: 0.0001, 0.0010); Job Demand: effect = 0.0003 (95 %CI: 0.0001, 0.0007]. Only the mediating effect of physical activity in the job stress-migraine link remained after further adjustments including socioeconomic factors, BMI, smoking, and the exclusion of major chronic diseases. CONCLUSION: In the ELSA-Brasil study, physical activity reversed the link between job stress and migraine independently of systemic inflammation, while the LTPA-mediated downregulation of GlycA was associated with lower job stress-related TTH.
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Biomarcadores , Proteína C-Reativa , Exercício Físico , Inflamação , Análise de Mediação , Estresse Ocupacional , Humanos , Masculino , Feminino , Brasil/epidemiologia , Pessoa de Meia-Idade , Inflamação/metabolismo , Inflamação/sangue , Adulto , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Estudos Transversais , Exercício Físico/fisiologia , Biomarcadores/sangue , Estresse Ocupacional/epidemiologia , Estudos Longitudinais , Estresse Psicológico/metabolismo , Cefaleia do Tipo Tensional/epidemiologia , Cefaleia do Tipo Tensional/sangue , Transtornos de Enxaqueca/epidemiologia , Cefaleia/epidemiologia , Cefaleia/metabolismo , IdosoAssuntos
Publicações Periódicas como Assunto , Psiquiatria , Brasil , Psiquiatria/tendências , HumanosRESUMO
Importance: Transcranial direct current stimulation (tDCS) is moderately effective for depression when applied by trained staff. It is not known whether self-applied tDCS, combined or not with a digital psychological intervention, is also effective. Objective: To determine whether fully unsupervised home-use tDCS, combined with a digital psychological intervention or digital placebo, is effective for a major depressive episode. Design, Setting, and Participants: This was a double-blinded, sham-controlled, randomized clinical trial with 3 arms: (1) home-use tDCS plus a digital psychological intervention (double active); (2) home-use tDCS plus digital placebo (tDCS only), and (3) sham home-use tDCS plus digital placebo (double sham). The study was conducted between April 2021 and October 2022 at participants' homes and at Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. Included participants were aged 18 to 59 years with major depression and a Hamilton Depression Rating Scale, 17-item version (HDRS-17), score above 16, a minimum of 8 years of education, and access to a smartphone and internet at home. Exclusion criteria were other psychiatric disorders, except for anxiety; neurologic or clinical disorders; and tDCS contraindications. Interventions: tDCS was administered in 2-mA, 30-minute prefrontal sessions for 15 consecutive weekdays (1-mA, 90-second duration for sham) and twice-weekly sessions for 3 weeks. The digital intervention consisted of 46 sessions based on behavioral therapy. Digital placebo was internet browsing. Main Outcomes and Measures: Change in HDRS-17 score at week 6. Results: Of 837 volunteers screened, 210 participants were enrolled (180 [86%] female; mean [SD] age, 38.9 [9.3] years) and allocated to double active (n = 64), tDCS only (n = 73), or double sham (n = 73). Of the 210 participants enrolled, 199 finished the trial. Linear mixed-effects models did not reveal statistically significant group differences in treatment by time interactions for HDRS-17 scores, and the estimated effect sizes between groups were as follows: double active vs tDCS only (Cohen d, 0.05; 95% CI, -0.48 to 0.58; P = .86), double active vs double sham (Cohen d, -0.20; 95% CI, -0.73 to 0.34; P = .47), and tDCS only vs double sham (Cohen d, -0.25; 95% CI, -0.76 to 0.27; P = .35). Skin redness and heat or burning sensations were more frequent in the double active and tDCS only groups. One nonfatal suicide attempt occurred in the tDCS only group. Conclusions and Relevance: Unsupervised home-use tDCS combined with a digital psychological intervention or digital placebo was not found to be superior to sham for treatment of a major depressive episode in this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04889976.
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Transtorno Depressivo Maior , Estimulação Transcraniana por Corrente Contínua , Humanos , Feminino , Adulto , Masculino , Transtorno Depressivo Maior/tratamento farmacológico , Resultado do Tratamento , Método Duplo-Cego , BrasilRESUMO
Importance: The period from childhood to early adulthood involves increased susceptibility to the onset of mental disorders, with implications for policy making that may be better appreciated by disaggregated analyses of narrow age groups. Objective: To estimate the global prevalence and years lived with disability (YLDs) associated with mental disorders and substance use disorders (SUDs) across 4 age groups using data from the 2019 Global Burden of Disease (GBD) study. Design, Setting, and Participants: Data from the 2019 GBD study were used for analysis of mental disorders and SUDs. Results were stratified by age group (age 5 to 9, 10 to 14, 15 to 19, and 20 to 24 years) and sex. Data for the 2019 GBD study were collected up to 2018, and data were analyzed for this article from April 2022 to September 2023. Exposure: Age 5 to 9 years, 10 to 14 years, 15 to 19 years, and 20 to 24 years. Main Outcomes and Measures: Prevalence rates with 95% uncertainty intervals (95% UIs) and number of YLDs. Results: Globally in 2019, 293 million of 2516 million individuals aged 5 to 24 years had at least 1 mental disorder, and 31 million had an SUD. The mean prevalence was 11.63% for mental disorders and 1.22% for SUDs. For the narrower age groups, the prevalence of mental disorders was 6.80% (95% UI, 5.58-8.03) for those aged 5 to 9 years, 12.40% (95% UI, 10.62-14.59) for those aged 10 to 14 years, 13.96% (95% UI, 12.36-15.78) for those aged 15 to 19 years, and 13.63% (95% UI, 11.90-15.53) for those aged 20 to 24 years. The prevalence of each individual disorder also varied by age groups; sex-specific patterns varied to some extent by age. Mental disorders accounted for 31.14 million of 153.59 million YLDs (20.27% of YLDs from all causes). SUDs accounted for 4.30 million YLDs (2.80% of YLDs from all causes). Over the entire life course, 24.85% of all YLDs attributable to mental disorders were recorded before age 25 years. Conclusions and Relevance: An analytical framework that relies on stratified age groups should be adopted for examination of mental disorders and SUDs from childhood to early adulthood. Given the implications of the early onset and lifetime burden of mental disorders and SUDs, age-disaggregated data are essential for the understanding of vulnerability and effective prevention and intervention initiatives.
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Transtornos Mentais , Transtornos Relacionados ao Uso de Substâncias , Masculino , Feminino , Humanos , Criança , Adolescente , Adulto , Carga Global da Doença , Saúde Mental , Prevalência , Anos de Vida Ajustados por Qualidade de Vida , Saúde Global , Transtornos Mentais/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
OBJECTIVE: This study investigated the incidence of suicidal ideation and its associated risk factors in the São Paulo state of ELSA-Brasil cohort during the COVID-19 pandemic. METHODS: During a pre-pandemic ELSA-Brasil onsite assessment in 2016-2018 (wave 3) and a pandemic online assessment in May-July 2020 (wave COVID), we assessed suicidal ideation using the Clinical Interview Scheduled-Revised (CIS-R). Single and multi predictor logistic regressions were performed using sociodemographic characteristics, household finance impact during pandemic, presence of previous chronic diseases, alcohol abuse, adverse childhood experiences (ACE), living alone, and previous CMD as predictors. Suicidal ideation incidence was used as outcome. RESULTS: Out of 4191 participants of wave 3, 2117 (50.5%) answered wave COVID. There was a threefold increase in suicide ideation, from 34 (1.8%) to 104 (5.6%).In multiple predictor models, we found that previous CMD (OR 7.17; 95% CI 4.43 - 11.58) and ACE (OR 1.72; 95% CI 1.09 - 2.72) increased the odds of incident suicidal ideation. The sociodemographic predictors female sex, younger age and low income were significant risk factors only in the single predictor model. Conclusions These findings underscore the importance of monitoring and supporting individuals who suffered ACE and have a history of mental health disorders. This is especially critical in times of heightened societal stress, such as the COVID-19 pandemic. CONCLUSIONS: These findings underscore the importance of monitoring and supporting individuals who suffered ACE and have a history of mental health disorders. This is especially critical in times of heightened societal stress, such as the COVID-19 pandemic.
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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.
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Depression is one of the main public health problems in the world, having a high prevalence and being considered the main cause of disability. An important portion of patients does not respond to treatment with the initial trial of conventional antidepressants in the current depressive episode of moderate to severe intensity, which characterizes treatment-resistant depression. In this context, non-invasive neuromodulation procedures use an electric current or magnetic field to modulate the central nervous system, and they represent a new option for patients with treatment-resistant depression.
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Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Humanos , Estimulação Magnética Transcraniana/métodos , Depressão , Transtorno Depressivo Resistente a Tratamento/terapia , Transtorno Depressivo Resistente a Tratamento/etiologia , Encéfalo , Resultado do TratamentoRESUMO
Objectives: To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis. Results: The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%. Conclusion: Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention. Registration number: PROSPERO CRD42018092033.
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OBJECTIVES: To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis. RESULTS: The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%. CONCLUSION: Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention.
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Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Prevalência , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Resistência a MedicamentosRESUMO
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. CONCLUSION: Our results highlight the need for a standardized tDCS protocol in MDD clinical trials.
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Transtorno Depressivo Maior , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Córtex Pré-Frontal , Transtorno Depressivo Maior/terapia , Encéfalo , AntidepressivosRESUMO
OBJECTIVES: Potentially inappropriate medications (PIM), especially those with potential effects on the central nervous system, can increase the risk of cognitive impairment. We investigated the association of the use of PIM and PIM that may impair cognition (PIM-Cog) with cognitive performance among older adults. METHODS: In this cross-sectional study with 2,626 participants, PIM and PIM-Cog were defined by the 2019 American Geriatrics Society Beers criteria. We calculated global cognition and memory, verbal fluency, and Trail Making Test B version (TMT-B) z-scores. Linear regression models adjusted for sociodemographic and clinical variables were used to investigate the association between PIM and cognition. RESULTS: 27% and 7% of the sample (mean age = 65.1 ± 4.1 years old, 54% women, and 61% White) used at least one PIM and PIM-cog, respectively. PIM was associated with poor performance in the TMT-B (ß = -0.17, 95% Cl = -0.29; -0.05, p = 0.007). PIM-Cog was also associated with poor TMT-B performance (ß = -0.08, 95% Cl = -0.15; -0.01, p = 0.025). CONCLUSION: The use of PIM and PIM-Cog was associated with poor executive function among older adults. The review of PIM use and the deprescription of these drugs may be an effective way to improve cognitive function.
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Disfunção Cognitiva , Lista de Medicamentos Potencialmente Inapropriados , Humanos , Feminino , Estados Unidos , Idoso , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Prescrição Inadequada , Cognição , Disfunção Cognitiva/induzido quimicamenteRESUMO
Background: To identify multimorbidity patterns, by sex, according to sociodemographic and lifestyle in ELSA-Brasil. Methods: Cross-sectional study with 14,516 participants from ELSA-Brasil (2008-2010). Fuzzy c-means was used to identify multimorbidity patterns of 2+ chronic morbidities, where the consequent morbidity had to occur in at least 5% of all cases. Association rule (O/E≥1.5) was used to identify co-occurrence of morbidities, in each cluster, by sociodemographic and lifestyle factors. Results: The prevalence of multimorbidity was higher in women (73.7%) compared to men (65.3%). Among women, cluster 1 was characterized by hypertension/diabetes (13.2%); cluster 2 had no overrepresented morbidity; and cluster 3 all participants had kidney disease. Among men, cluster 1 was characterized by cirrhosis/hepatitis/obesity; cluster 2, most combinations included kidney disease/migraine (6.6%); cluster 3, no pattern reached association ratio; cluster 4 predominated co-occurrence of hypertension/rheumatic fever, and hypertension/dyslipidemia; cluster 5 predominated diabetes and obesity, and combinations with hypertension (8.8%); and cluster 6 presented combinations of diabetes/hypertension/heart attack/angina/heart failure. Clusters were characterized by higher prevalence of adults, married and participants with university degrees. Conclusion: Hypertension/diabetes/obesity were highly co-occurred, in both sexes. Yet, for men, morbidities like cirrhosis/hepatitis were commonly clustered with obesity and diabetes; and kidney disease was commonly clustered with migraine and common mental disorders. The study advances in understanding multimorbidity patterns, benefiting simultaneously or gradually prevention of diseases and multidisciplinary care responses.
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AIM: To analyze the prospective dose-response relationships between total and domain-specific physical activity (PA) with incident clinical depression. METHODS: We used data from two waves (Wave 1: August/2008-December 2010; Wave 2: September/2012-December/2014) of the Brazilian Longitudinal Health Study (ELSA-Brasil) cohort study. Self-reported PA (total, transport, and leisure-time) was the main exposure. Incident clinical depression (new cases of depression between waves) was assessed through the Clinical Interview Schedule-Revised (CIS-R). Poisson regression models, adjusting for potential confounders, were used for data analysis. RESULTS: In 12,709 adults (53.8 % women, mean age: 51.9 ± 9.0), moderate and high volumes of total PA (1-149 min/week: RR = 0.81, 0.58-1.13, 150-299 min/week: RR = 0.55, 95%CI: 0.40-0.76; ≥300 min/week: RR = 0.64, 95%CI: 0.52-0.80), and any volume of leisure-time PA (1-149 min/week: RR = 0.65, 95%CI: 0.50-0.83; 150-299 min/week: RR = 0.67, 95%CI: 0.52-0.88; RR = 0.61, 95%CI: 0.45-0.82) were associated with a lower risk of incident clinical depression. Transport PA protective only in the lower category (0.1-4.4 mMET-h/wk) (RR = 0.71, 95%CI: 0.54-0.94). LIMITATIONS: Other PA domains such as occupational and domestic were not assessed; the use of self-report measures for PA which may be subject to bias and recall issues; lack of assessment of additional potential confounders, such as sedentary behavior and family history of depression. CONCLUSION: Total and leisure-time PA were associated with lower incidence of clinical depression, even at lower doses. Low, moderate, and high volumes of total and leisure-time PA were associated with lower risk of incident clinical depression. Public health PA interventions aiming to prevent development of clinical depression should consider focusing on leisure-time PA.
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Depressão , Exercício Físico , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos de Coortes , Seguimentos , Estudos Prospectivos , Brasil/epidemiologia , Depressão/epidemiologia , Exercício Físico/fisiologia , Atividades de LazerRESUMO
BACKGROUND: New-onset chronic pain has been acknowledged as part of the post-COVID-19 condition. However, available fine-grained data about its clinical phenotype, trajectories and main associated characteristics remain scarce. We described the distinct temporal evolutions of post-COVID-19 pain and their epidemiological and phenotypical features. METHODS: A prospective cross-sectional study enrolled post-COVID-19 condition patients (i.e. who had persisting COVID-19-related symptoms over 30 days since their first positive laboratory test), whose COVID-19 diagnosis had been supported by RT-PCR of oral/nasopharyngeal swab or serology. They underwent in-person evaluations with a structured interview, pain and quality-of-life-related questionnaires and thorough physical examination. Chronic pain (CP) and probable neuropathic pain (NP) were defined according to IASP criteria. RESULTS: The present study included 226 individuals, 177 (78.3%) of whom presented over 3 months since their first COVID-19 symptom. New-onset pain occurred in 170 (75.2%) participants and was chronic in 116 (68.2%). A chronic course was associated with COVID-19-related hospitalization, new-onset fatigue, lower cognitive performance, motor and thermal sensory deficits, mood and sleep impairments and overall lower quality-of-life levels. Probable NP occurred in only 7.6% new-onset pain patients, and was associated with pain chronification, new-onset fatigue, motor and thermal sensory deficits, mechanical allodynia and lower rates of SARS-CoV-2 vaccination. Previous CP was reported by 86 (38.1%) individuals and had aggravated after the infection in 66 (76.7%) of them, which was associated with orthostatic hypotension. CONCLUSIONS: Post-COVID pain phenomena follow different paths, which are associated with specific clinical and epidemiological features, and possibly distinct underlying mechanisms, prognostic and therapeutic implications. SIGNIFICANCE: COVID-19-related pain usually follows a chronic course and is non-neuropathic. Its possible courses and phenotypes are associated with distinct clinical and epidemiological features. This suggests differing underlying mechanisms, which may have significant prognostic and therapeutic implications.
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COVID-19 , Dor Crônica , Neuralgia , Humanos , COVID-19/complicações , SARS-CoV-2 , Estudos Transversais , Teste para COVID-19 , Dor Crônica/epidemiologia , Dor Crônica/etiologia , Estudos Prospectivos , Vacinas contra COVID-19 , Neuralgia/epidemiologia , Neuralgia/etiologiaRESUMO
BACKGROUND: South America's substance use profile, poverty, income inequality, and cocaine-supplier role make it a unique place for substance use research. This study investigated the burden of disease attributable to amphetamine use disorder, cannabis use disorder (CAD), cocaine use disorder, and opioid use disorder (OUD) in South America from 1990 to 2019, on the basis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: GBD 2019 estimated the incidence, prevalence, mortality, years of life lost (YLL), years of life lived with disability (YLD), and disability-adjusted life-years (DALYs) due to substance use disorders in each of the 12 South American countries (Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Guyana, Paraguay, Peru, Suriname, Uruguay, and Venezuela). Data were modelled using standardised tools (ie, the Cause of Death Ensemble model, spatio-temporal Gaussian process regression, and disease modelling meta-regression) to generate estimates of each quantity of interest by sex, location, and year. The analysis included comparisons by sex and country, and against regional and global estimates. FINDINGS: In 2019, the highest amphetamine use disorder burden per 100â000 population in South America was in Peru (66 DALYs). CAD DALY rates per 100â000 in South America were stable between 1990 and 2019, except in Chile and Colombia, which had the highest rates in 2019 (19 DALYs for Chile and 18 DALYs for Colombia). OUD DALYs per 100â000 increased during the period in Brazil and Peru, which in 2019 had the highest rates in South America (82 DALYs for Brazil and 70 DALYs for Peru). In 2019, Brazil had the highest cocaine use disorder DALYs per 100â000 (45 DALYs), nearly double its rate in 1990. DALY rates were higher in males than females for each substance use disorder, except in Paraguay. The overall burden of substance use disorders was higher in males than in females, mainly because of cocaine use disorder and CAD, whereas for amphetamine use disorder, the difference between sexes was minimal, and for OUD there was no difference. For males and females, the highest rate of substance use disorders DALYs per 100â000 was for OUD except in Argentina (in males, 58 DALYs for cocaine use disorder vs 52 DALYs for OUD) and in Paraguay (in females, 77 for amphetamine use disorder vs 50 for OUD). CAD DALY rates were generally the lowest among the substance use disorders for males and females. Amphetamine use disorder YLD rates were reasonably stable throughout the period and were highest in Peru, Paraguay, and Uruguay (>40 YLD per 100â000). For CAD, YLD rates were stable in all countries except Chile and Colombia. Cocaine use disorder YLD rates per 100â000 for the top four countries (Argentina, Uruguay, Chile, and Brazil) increased from 1990 to 2010 (eg, from 19 to 33 in Brazil), but decreased between 2010 and 2019 (eg, from 36 to 31 in Chile). For OUD, YLD rates showed a slight increase in most countries apart from Brazil, which increased from 52 in 1990 to 80 in 2019 and was top among the countries. Amphetamine use disorder YLL rates per 100â000 were highest in Suriname and Peru during the period, although in Suriname it increased from 2·7 in 2010 to 3·2 in 2019, whereas in Peru it decreased from 2·1 to 1·7. The highest YLL rate for cocaine use disorder was in Brazil, which increased from 3·7 in 1990 to 18·1 in 2019. Between 2000 and 2019, Chile and Uruguay showed the highest OUD YLL rates (11·6 for Chile and 10·9 for Uruguay). A high incidence of CAD was found in Chile, Colombia, Guyana, and Suriname. There were high incidences of amphetamine use disorder in Paraguay, cocaine use disorder in Argentina, and OUD in Ecuador. A decrease in annual prevalence for substance use disorders during the period was observed in Venezuela (amphetamine use disorder, CAD, and OUD), Brazil (CAD and amphetamine use disorder), Colombia (amphetamine use disorder and cocaine use disorder), Peru (amphetamine use disorder and cocaine use disorder), Chile and Suriname (amphetamine use disorder), Uruguay (CAD), and Bolivia (OUD). Overall, the cocaine use disorder burden stabilised then decreased. OUD was less prevalent than other substance use disorders but its burden was the highest. INTERPRETATION: The decrease in the burden of cocaine use disorder probably reflects the success of national standardised treatment programmes. Programmes for amphetamine use disorder, CAD, and OUD management should be improved. We did not find an increase in CAD burden in Uruguay, the country with the highest degree of cannabis decriminalisation in the region. Countries in South America should improve monitoring of substance use disorders, including regular surveys to provide more accurate data on which to base policy decisions. FUNDING: The Bill & Melinda Gates Foundation.
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Cannabis , Transtornos Relacionados ao Uso de Substâncias , Masculino , Feminino , Humanos , Carga Global da Doença , Anos de Vida Ajustados por Qualidade de Vida , Brasil , Anfetaminas , Saúde GlobalRESUMO
Non-invasive brain stimulation (NIBS) techniques have been increasingly used over the dorsolateral prefrontal cortex (DLPFC) to enhance working memory (WM) performance. Notwithstanding, NIBS protocols have shown either small or inconclusive cognitive effects on healthy and neuropsychiatric samples. Therefore, we assessed working memory performance and safety of transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and both therapies combined vs placebo over the neuronavigated left DLPFC of healthy participants. Twenty-four subjects were included to randomly undergo four sessions of NIBS, once a week: tDCS alone, iTBS alone, combined protocol and placebo. The 2-back task and an adverse effect scale were applied after each NIBS session. Results revealed a significantly faster response for iTBS (b= -21.49, p= 0.04), but not for tDCS and for the interaction tDCS vs. iTBS (b= 13.67, p= 0.26 and b= 40.5, p= 0.20, respectively). No changes were observed for accuracy and no serious adverse effects were found among protocols. Although tolerable, an absence of synergistic effects for the combined protocol was seen. Nonetheless, future trials accessing different outcomes for the combined protocols, as well as studies investigating iTBS over the left DLPFC for cognition and exploring sources of variability for tDCS are encouraged.
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OBJECTIVES: Studies have suggested Brain-Derived Neurotrophic Factors (BDNF) increase after electroconvulsive therapy (ECT) although they were methodologically limited and enrolled small sample sizes. We aimed at updating a systematic review and meta-analysis to explore BDNF changes after ECT for the treatment of depression. METHODS: PubMed, PsycInfo, Embase and Global health were searched (March, 2021). Clinical trials that measured BDNF in the blood before and after ECT in adults (≥ 18 years old) with depression (major depressive disorder or bipolar disorder) were eligible. Data were pooled through random-effects meta-analyses. RESULTS: Twenty-eight studies involving 778 participants were included. Meta-analysis showed a significant increase in BDNF levels after ECT (Hedges' g = 0.28; 95% CI: 0.10, 0.46) while there was evidence of significant heterogeneity (I2 = 67.64%) but not publication bias/small-study effect. Subgroup analyses and meta-regressions were underpowered to detect significant differences. Meta-analysis of depression severity scores demonstrated a considerable larger treatment effect in reducing depressive symptoms after ECT (Hedge's g = -3.72 95% CI: -4.23, -3.21). CONCLUSION: This updated review showed that BDNF blood levels increased after ECT treatment. However, there was still evidence of substantial heterogeneity and there were limited sample sizes to investigate factors driving the variability of effects across studies. Importantly, the increase in BDNF levels was substantially smaller than the observed in depressive symptomatology, which could be indicative that the former was independent than the latter. Additional studies with larger sample sizes are currently required.