Objective: We assessed the effect of N-acetylcysteine, as an adjuvant treatment, on treatment adherence (primary outcome) according to peripheral biomarkers and clinical improvement (secondary outcomes) in patients with alcohol use disorder. Methods: A 9-week randomized, double-blind, placebo-controlled clinical trial was conducted on 53 (n = 25 N-acetylcysteine, n = 28 placebo) inpatients with alcohol use disorder. Neuropeptide Y, oxidative stress and inflammatory biomarkers, and hepatic parameters were analyzed at 3 time points. Results: Seventeen (60.7%) patients in the placebo group and 16 (64%) patients in the N-acetylcysteine group completed the trial. Hepatic biomarker levels changed significantly over time (p < 0.001). Oxidized glutathione levels at admission were lower in the N-acetylcysteine group (ppairwise = 0.043). By the end of the study, both groups had similar oxidized glutathione levels (p = 0.868), and oxidized glutathione levels were lower in the placebo group. At the end of the intervention, superoxide dismutase activity had decreased and neuropeptide Y levels had increased in the N-acetylcysteine group. Both groups showed similar mean time to relapse, treatment adherence, and clinical improvement. Conclusions: Our findings reinforce the effects of alcohol on oxidative stress and neuropeptide Y parameters. However, our sample size may limit the generalizability of the results, especially for clinical outcomes. Future randomized clinical trials including patients with less severe alcohol use disorder and longer follow-up may be needed to determine whether N-acetylcysteine could help reduce the mental health burden of this disorder. Clinical Trial Registration: NCT03018236.

Objective: This study investigated the relationship between impulsivity and early trauma through a network analysis in individuals diagnosed with different substance use disorders. Methods: In a cross-sectional design, the sample included 556 men with substance use disorders (195 with alcohol use, 157 with cocaine/crack use, and 214 with polysubstance use). Early trauma and impulsive behavior were assessed using the Childhood Trauma Questionnaire and the Barratt Impulsiveness Scale, respectively. The connection between trauma and impulsivity was assessed using network analysis through a fused graphical lasso algorithm. Results: No connection was observed between impulsivity and trauma networks in individuals with alcohol use disorder. In those with cocaine use disorder, networks were linked through the motor domain and sexual abuse nodes. Inverse connections were observed between the emotional neglect node and perseverance, but not the non-planning node. In polysubstance use, the connection between impulsivity and trauma networks was weak, with the cognitive complexity node connecting to the trauma network through physical abuse. There connections were inversely proportional between the motor domain and emotional neglect nodes, as well as between cognitive instability and physical neglect. Conclusion: Our results suggest that the relationship between the type of early (childhood) trauma and the expression of impulsivity could lead to different substance use profiles.

ABSTRACT Objective: the study aimed to evaluate maternal-fetal attachment, childhood traumas, and character strengths in women who used crack during pregnancy admitted to a public hospital in Porto Alegre. Methods: twenty-four pregnant women were interviewed, in a cross-sectional design, and were applied the instruments: Childhood Trauma Questionnaire (CTQ), Maternal-Fetal Attachment Scale and the Characters Strenghts Scale. Results: a medium or high degree of maternal-fetal attachment and a high frequency of childhood traumas was found, standing out emotional abuse and physical neglect. There was no significant association between maternal-fetal bonding and the occurrence of trauma in childhood. The character strengths that obtained the highest scores among the pregnant women were bravery, authenticity and love. Conclusion: despite the adverse conditions, it was observed that the pregnant women had a high maternal-fetal attachment. Identifying the strengths that stood out may contribute to the more effective treatment of these women, this being a good strategy in the planning of public health policies.

RESUMO Objetivos: o estudo buscou avaliar o apego materno-fetal, os traumas na infância e as forças de caráter em mulheres que fizeram uso de crack durante a gestação, internadas em hospital público, em Porto Alegre. Métodos: foram entrevistadas 24 gestantes, em um delineamento transversal, e aplicados os instrumentos: Questionário sobre Traumas na Infância, Escala de Apego Materno-Fetal e Escala de Forças e Virtudes. Resultados: foi encontrado um grau médio ou alto de apego materno-fetal e alta frequência de traumas sofridos na infância, destacando-se abuso emocional e negligência física. Não houve associação significativa entre o vínculo materno fetal e a ocorrência de traumas na infância. As forças de caráter com maior escore foram: bravura, autenticidade e amor. Conclusões: Apesar das condições adversas, foi observado que as gestantes tinham um elevado apego materno-fetal. A identificação das forças de caráter que se destacaram pode ajudar para um tratamento mais efetivo dessas mulheres, sendo esta uma boa estratégia no planejamento de políticas de saúde pública.

Resumen: Introducción: Los videojuegos electrónicos son reconocidos actualmente como un problema de salud mental, especialmente dentro de la comunidad LGBTQIA+. Objetivo: Explorar los efectos del trastorno de juego (gaming disorder) en la población LGBTQIA+. Método: La revisión narrativa abordó los hábitos de juego y el gaming disorder en minorías sexuales y de género, utilizando PubMed, Google Scholar, Embase y Web of Science. De las 1640 investigaciones, solo 3 se centraron en el gaming disorder en esta población. Resultado: Los consumidores LGBTQ+ gastan más en juegos digitales. Los jugadores LGBTQIA+ consumen más juegos de exploración de identidad, posiblemente relacionados con el estrés de minoría. Discusión: Las minorías sexuales enfrentan un mayor riesgo de gaming disorder. Para los individuos LGBTQIA+, los juegos pueden servir como un escape y plataforma de apoyo, pero el uso problemático puede estar asociado con resultados psiquiátricos negativos. Conclusión: Los juegos en línea tienen el potencial como herramientas de apoyo para las minorías, pero la evidencia es limitada. Se requiere más investigación para comprender mejor la relación entre el uso de juegos y la salud mental en la población LGBTQIA+.

Resumo: Introdução: Os jogos eletrônicos são agora reconhecidos como um problema de saúde mental, especialmente entre a comunidade LGBTQIA+. Objetivo: explorar os efeitos do transtorno de jogo (gaming disorder) na população LGBTQIA+. Método: A revisão narrativa abordou hábitos de jogo e gaming disorder em minorias sexuais e de gênero, usando PubMed, Google Scholar, Embase e Web of Science. Das 1640 pesquisas, apenas 3 abordaram gaming disorder nessa população. Resultado: consumidores LGBTQ+ gastam mais em jogos digitais. Jogadores LGBTQIA+ consomem mais jogos de exploração de identidade, possivelmente relacionados ao estresse de minoria. Discussão: minorias sexuais têm maior risco de gaming disorder. Para indivíduos LGBTQIA+, os jogos podem servir como escape e plataforma de apoio, mas o uso problemático pode estar associado a desfechos psiquiátricos negativos. Conclusão: Os jogos online têm o potencial de serem ferramentas de apoio para minorias, no entanto, as evidências são limitadas. É necessária mais pesquisa para compreender melhor a relação entre o uso de jogos e a saúde mental da população LGBTQIA+.

Abstract: Introduction: Electronic games are now recognized as a mental health issue, especially within the LGBTQIA+ community. Objective: To explore the effects of gaming disorder in the LGBTQIA+ population. Method: The narrative review addressed gaming habits and gaming disorder in sexual and gender minorities, utilizing PubMed, Google Scholar, Embase, and Web of Science. Out of 1640 studies, only 3 focused on gaming disorder in this population. Result: LGBTQ+ consumers spend more on digital games. LGBTQIA+ players engage more in identity exploration games, possibly linked to minority stress. Discussion: Sexual minorities face a higher risk of gaming disorder. For LGBTQIA+ individuals, games can serve as an escape and support platform, but problematic use may be associated with negative psychiatric outcomes. Conclusion: Online games have the potential as support tools for minorities, but evidence is limited. Further research is needed to better understand the relationship between game use and mental health in the LGBTQIA+ population.

Abstract Introduction High rates of early hospital discharge are often observed in crack cocaine users and are related to adverse outcomes and increased public spending. This study evaluated clinical and sociodemographic factors associated with early treatment discharge among crack users. Methods The sample comprised 308 men diagnosed with crack cocaine use disorder (crack only), aged 18 to 65 years, admitted between 2013 and 2017 to a male-only hospital unit to treat substance use disorders. Sociodemographic and clinical data were obtained using the Addiction Severity Index, 6th version, and a Sociodemographic Questionnaire. Results Early discharge (within 7 days) was significantly associated with lack of own income, insufficient family support, being single, and recent homelessness. Regarding drug use, lower treatment retention was related to younger age of crack use onset, recent alcohol use, and nicotine use. Factors such as age, skin color, and educational level showed no relation to the outcome. Conclusion Our findings suggest that presence of characteristics verifiable at the time of admission may be related to crack users’ treatment retention. Identification of these factors can contribute to target interventions in order to improve treatment adherence in crack cocaine users. spending 30 only, only , only) 1 6 years 201 maleonly male disorders Index th version Questionnaire within days income support single homelessness onset color outcome 3 20 2

Abstract In much of the West, including Brazil, drug use has increased since social distancing began in response to the pandemic. Use of smoked and modified drugs, and their impacts on health, may contribute to aggravate the effects of the pandemic. However, studies on the relationship between use of smoked drugs and the new coronavirus are still scarce and have not received enough attention in global health recommendations. This paper aims to briefly review the relationship between use of smoked drugs and acute respiratory syndrome coronavirus 2 [SARS-CoV-2]. Recent studies also suggest that drug consumption increases the risk of contamination by SARS-CoV-2 and leads to worse prognosis, particularly consumption of drugs that affect lung function. Use of smoked drugs, especially tobacco, is strongly associated with lung diseases that are risk factors for contamination by SARS-CoV-2. It is essential to develop strategies based on specific characteristics of drug users and for mental health professionals to be included in strategic teams. It is also necessary to invest in information campaigns regarding risks and prevention of harm caused by smoked drugs as well as to design strategies that facilitate access to psychosocial treatment during the pandemic. West Brazil pandemic However recommendations SARSCoV2. SARSCoV2 SARSCoV SARS CoV . [SARS-CoV-2] SARS-CoV- prognosis function tobacco 2. teams [SARS-CoV-2 SARS-CoV [SARS-CoV- [SARS-CoV

Abstract Introduction Consumption of substances has been associated with cognitive impairment. The Mini Mental State Examination (MMSE) is an easy-to-apply screening tool used to assess cognitive functions. Objectives To evaluate the cognitive performance of individuals with alcohol (AUD) and/or crack cocaine use disorder (CUD) and polysubstance use using the MMSE and to investigate the impact of substance use profile and the moderation effect of educational level on MMSE performance. Methods Cross-sectional study with 508 adult male inpatients diagnosed with substance use disorders (245 with AUD, 85 with CUD, and 178 with polysubstance use). Cognitive performance was assessed using the MMSE scale (total and composite scores). Results Individuals with AUD had worse total MMSE scores and scored worse for all three MMSE components compared to individuals with polysubstance use (p < 0.001, oral/written language comprehension, p < 0.001, attention/memory, and p = 0.007, motor functions). MMSE scores were positively correlated with educational level (p < 0.017), but were not associated with age, recent drug use, or years of drug use. Educational level moderated the impact of substance use on MMSE performance, especially total score and composite language comprehension score. Individuals with a low educational level (≤ 8 years) had worse performance than those with a high educational level (≥ 9 years), mainly in individuals with AUD (p < 0.001). Discussion Individuals with a low educational level and alcohol use are more prone to present cognitive impairment than crack cocaine users, especially involving language aspects. Better-preserved cognitive function could impact treatment adherence and might guide the decision of therapeutic strategies.

Abstract Alcohol Use Disorder (AUD) is a highly prevalent condition worldwide that produces a wide range of pathophysiological consequences, with a critical impact on health and social issues. Alcohol influences gene expression through epigenetic changes mainly through DNA methylation. In this sense, levels of 5-methylcytosine (5-mC), namely Global DNA methylation (GMe), which can be influenced by environmental and hormonal effects, represent a putative biological mechanism underlying alcohol effects. Our aim was to investigate the influence of AUD diagnosis and alcohol patterns (i.e., years of addiction, use in the last 30 days, and alcohol severity) on GMe levels. The sample consisted of 256 men diagnosed with AUD and 361 men without AUD. DNA samples from peripheral blood were used to assess GMe levels, measured through the levels of 5-mC using high-performance liquid chromatography. Results from multiple linear regression analysis indicated that the presence of AUD was associated with lower GMe levels (beta=-0.155, p=0.011). Other alcohol-related outcomes were not associated with DNA methylation. Our findings are consistent with the hypothesis that the impact of chronic and heavy alcohol use in GMe could be a potential mechanism mediating the multiple organ damages related to AUD.

Objectives: To compare suicide rates observed in Brazil after the onset of the COVID-19 pandemic with the estimated rate based on suicide deaths between 2010 and 2020, and identify sociodemographic variables associated with this outcome. Methods: Ecological time-series study. Data were obtained from Brazilian Unified Health System Department of Information Technology (DATASUS), with the structural break of the data set in March 2020. The number of actual suicides observed and the number of expected suicides if there were no COVID-19 pandemic were analyzed through bayesian structural time series modeling. Results: The overall incidence of suicides in Brazil remained stable after the start of the COVID-19 pandemic compared to what would be expected. However, there was a significant increase in suicide deaths among women (6.9%) and older adult (9.1%). Analysis by macro-regions of the country showed significant increases in suicide deaths in the Center-West (7.4%), Northeast (5.7%), and Southeast (10%). Stratified analyses revealed differences according to age, sex, education, and skin color. Conclusions: Despite stability in the overall number of suicides, this phenomenon occurs heterogeneously among different population groups and regions of Brazil. Rates have increased in populations with a history of poor access to health, which may have been more severely impacted by the pandemic.

Objective: This study aimed to evaluate whether progression from first drug use to crack-cocaine use differs according to gender, and whether the report of sexual or physical violence impacts the time of progression. Methods: We interviewed 896 crack-cocaine users (548 men; 348 women) from addiction treatment units. Cox regression models evaluated the time of progression from first drug use to crack use. We analyzed gender differences according to the absence or presence of sexual or physical violence, also considering whether violence, when present, had occurred before or after the onset of crack use. Results: Women presented a faster progression to crack use regardless of exposure to sexual or physical violence (p < 0.05). Compared to unexposed men, there was a similar progression for men exposed to sexual or physical violence before the first use of crack (p = 0.167 and p = 0.393, respectively). In both genders, we observed a faster progression among individuals exposed to these types of violence after the onset of crack use (p < 0.01). Conclusions: We found a faster progression to crack use among women and among individuals exposed to sexual and physical violence after the onset of crack use. These results encourage differentiated treatment strategies, focused on gender and individual characteristics.

Objective: To assess differences in blood inflammatory cytokines between people with alcohol use disorder (AUD) and healthy controls (HC). Methods: Searches were performed from inception through April 14, 2021. Meta-analyses with random-effects models were used to calculate the standardized mean difference ([SMD], 95%CI), and potential sources of heterogeneity were explored trough meta-regressions and subgroup analysis. Results: The meta-analysis included 23 studies on the following 14 cytokines: tumor necrosis factor (TNF)-α, IL-1, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL15, interferon (IFN)-γ and sCD14. There were significantly higher concentrations of IL-6 (n=462 AUD and 408 HC; SMD = 0.523; 95%CI 0.136-0.909; p = 0.008) in AUD than HC. No significant differences were found in the other 13 cytokines. Conclusion: We found that IL-6 levels were significantly higher in individuals with AUD than HC and that other cytokines were not altered. This can be explained by the small number of studies, their methodological heterogeneity, and confounding factors (active use, abstinence, quantity, and physical or psychiatric illnesses, for example). Despite a great deal of evidence about alcohol and inflammatory diseases, studies assessing the role of neuroimmune signaling in the development and severity of AUD are still lacking.

Objective: This study reviewed and analyzed the prevalence of suicidal behaviors among cocaine users who sought health services. Methods: This is a systematic review and meta-analysis of studies published until January 2021. PubMed/MEDLINE, Scopus, Embase, PsycINFO, and LILACS were searched. The inclusion criteria were observational (retrospective or prospective), case-control, and/or cross-sectional reports that contained samples of cocaine users aged over 14 years who were assessed in health facilities or were in treatment. The random-effects model was used to calculate the overall prevalence of suicidal behavior with a 95% confidence interval. Subgroup analysis was conducted to investigate sources of heterogeneity. Results: Twenty articles were included, yielding a total of 2,252 cocaine users. The estimated prevalence was 43.59% (95%CI 31.10-57.38) for suicidal ideation and 27.71% (95%CI 21.63-34.73) for suicide attempts. High heterogeneity was found between studies for both outcomes (I2 ≥ 93%), although subgroup analysis considering the quality of the studies showed a significant difference in suicide attempts (p = 0.03). Conclusion: Cocaine use can be considered a risk factor for suicidal behavior, and prevention and early screening measures should be implemented to facilitate adequate treatment.

Objective: To compare the prevalence and subtypes of childhood maltreatment (CM) between individuals with and without substance use disorder (SUD) and investigate the influence of different traumas on the preferential use of substances and the severity of dependence. Methods: The sample consisted of 1,040 men with SUD (alcohol users [n=315], crack-cocaine users [n=406], multiple-substance users [n=319]) and 201 controls. The Childhood Trauma Questionnaire (CTQ) and the Addiction Severity Index-6 (ASI-6) were used to assess CM and drug-use patterns. Results: Individuals with SUD had a higher prevalence of CM than controls (63.4 vs. 28.1%, respectively). Exposure to physical trauma was associated with alcohol use disorder and severity of alcohol use. In contrast, emotional trauma was associated with use of multiple substances and severity of drug use in crack-cocaine users. Conclusions: This study corroborates the association of CM with SUD susceptibility. Our results suggest that the type of CM may influence preferential substance use and addiction severity. In this sense, physical traumas are more associated with alcohol use, while emotional and sexual traumas favor use of multiple drugs, especially crack cocaine. These findings may help the development of tailored prevention and intervention strategies.

Abstract Introduction Changes in brain-derived neurotrophic factor (BDNF) have been linked to the neuroadaptative consequences of chronic alcohol use and associated with disease severity and prognosis. Few studies have evaluated the influence of drug withdrawal and clinical and sociodemographic data on BDNF levels in severe alcohol users. Objectives Our goals were (1) to evaluate variation in BDNF levels during alcohol withdrawal and, (2) to assess the influence of putative confounding factors on BDNF levels. Methods Our sample consists of 62 men with alcohol use disorder undergoing a detoxification process. Serum BDNF levels were measured using a commercial sandwich-ELISA kit, at two points: before and after the detoxification period. Results We found an increase in BDNF levels during alcohol withdrawal (25.4±9.6 at admission vs. 29.8±10.2 ng/ml at discharge; p < 0.001), even after controlling for potential confounders (positive family history, number of days between blood sample collections, and age) (Generalized Estimating Equation: coefficient = -4.37, 95% confidence interval [95%CI] -6.3; -2.4; p < 0.001). Moreover, individuals who had first-degree relative with alcohol dependence had smaller increases in BDNF levels than individuals with no family history (14.8 [95%CI -5.3; 35.6] vs. 35.3 [95%CI 15.4; 74.8]; p = 0.005). Conclusions In summary, variation in BDNF levels seems to be influenced by withdrawal in severe alcohol users. A positive family history of alcohol dependence could also be a factor that influences variation in this biomarker.