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. Objective Methods crosssectional cross sectional design 55 195 (19 15 cocainecrack crack 21 use. . use) Scale respectively algorithm Results disorder nodes perseverance nonplanning non planning weak Conclusion childhood (childhood profiles 5 19 (1 1 2 (

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

RESUMO Objetivo: O uso de substâncias psicoativas pode levar a diversas consequências à saúde física e mental. O exercício físico é um importante aliado ao tratamento farmacológico e psicoterápico para o uso de substâncias. No entanto, a literatura ainda é escassa em relação às intervenções de longa duração. Dessa forma, este estudo objetiva descrever a aceitabilidade e os efeitos de uma intervenção de treinamento físico combinado (aeróbico e força). Métodos: Este estudo compreende um n-of-1 clinical trial que foi realizado com um indivíduo do sexo masculino, de 64 anos de idade, com transtorno por uso de álcool. O tratamento teve a duração de 12 semanas e avaliou a associação de intervenções multiprofissionais sobre a qualidade de vida, sintomas depressivos, comprometimento cognitivo e ansiedade. Resultados: O participante melhorou a qualidade de vida geral (12,5%), não foram encontradas alterações para sintomas depressivos, houve melhora na cognição (20%), bem como redução nos sintomas de ansiedade traço (16,2%) e estado (14,7%) do participante. Conclusões: Esses achados aludem à importância de recursos terapêuticos não medicamentosos como o exercício físico estruturado, associados às demais ofertas no tratamento para o transtorno por uso de álcool. Objetivo mental entanto forma aeróbico força. força . força) Métodos nof1 nof n of 1 n-of- masculino 6 idade álcool depressivos Resultados 12,5%, 125 12,5% , 5 (12,5%) 20%, 20 20% (20%) 16,2% 162 16 2 (16,2% 14,7% 147 14 7 (14,7% Conclusões estruturado n-of 12,5 (12,5% (20% 16,2 (16,2 14,7 (14,7 12, (12,5 (20 16, (16, 14, (14, (12, (2 (16 (14 (12 ( (1

ABSTRACT Objective: Substance misuse can lead to several consequences for physical and mental health. Physical exercise is an important ally to pharmacological and psychotherapeutic treatment for substance use. However, the literature is still scarce regarding long-term interventions. Thus, this study aims to describe the acceptability and effects of combined physical training intervention (aerobic and strength). Methods: This study comprises an n-of-1 clinical trial that was performed with a 64-year-old male individual with alcohol use disorder. The treatment lasted 12 weeks and evaluated the association of multidisciplinary interventions on quality of life, depressive symptoms, cognitive impairment, and anxiety. Results: The participant improved general quality of life (12.5%), no alterations were found for depressive symptoms, there was an improvement in cognition (20%), as well a reduction in the trait (16.2%) and state (14.7%) anxiety symptoms of the participant. Conclusions: These findings allude to the importance of non-drug therapeutic resources such as structured physical exercise, associated with other offers in the treatment of alcohol use disorder. Objective health However longterm long term Thus aerobic strength. strength . strength) Methods nof1 nof n 1 n-of- 64yearold yearold 64 year old disorder impairment Results 12.5%, 125 12.5% , 5 (12.5%) 20%, 20 20% (20%) 16.2% 162 16 2 (16.2% 14.7% 147 14 7 (14.7% Conclusions nondrug non drug n-of 6 12.5 (12.5% (20% 16.2 (16.2 14.7 (14.7 12. (12.5 (20 16. (16. 14. (14. (12. (2 (16 (14 (12 ( (1

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. (MMSE easytoapply easy apply functions (AUD andor CUD (CUD Crosssectional Cross sectional 50 245 (24 17 . use) scores. scores) 0001 0 001 0.001 oralwritten oral written attentionmemory attention memory attention/memory 0007 007 0.007 functions) 0.017, 0017 0.017 , 017 0.017) age ≤ ( ≥ years, 0.001. 0.001) users aspects Betterpreserved Better preserved strategies 5 24 (2 1 000 00 0.00 0.01 01 2 0.0 0.

Abstract The aim of this study was to describe the prevalence, clinicopathological, and prognostic features of acinic cell carcinoma (AciCC) of the oral and maxillofacial region. AciCC cases were retrospectively retrieved from 11 pathology centers of three different countries. Medical records were examined to extract demographic, clinical, pathologic, and follow-up information. A total of 75 cases were included. Females (65.33%) with a mean age of 45.51 years were mostly affected. The lesions usually presented as an asymptomatic (64.28%) nodule (95.66%) in the parotid gland (70.68%). The association of two histopathological patterns was the most common finding (48.93%) and the tumors presented mainly conventional histopathological grades (86.11%). Surgical treatment was performed in the majority of the cases (59.19%). Local recurrence was observed in 20% of the informed cases, regional metastasis in 30.43%, and distant metastasis in 12.50%. The statistical analysis showed that the cases with a solid histopathological pattern (p=0.01), high-grade transformation (p=0.008), recurrence (p=0.007), and regional metastasis (p=0.03) were associated with poor survival. In conclusion, high histopathological transformation, presence of nodal metastasis, and recurrence were prognostic factors for AciCC of the oral and maxillofacial region. prevalence clinicopathological (AciCC region 1 countries demographic clinical pathologic followup follow up information 7 included 65.33% 6533 65 33 (65.33% 4551 45 51 45.5 affected 64.28% 6428 64 28 (64.28% 95.66% 9566 95 66 (95.66% 70.68%. 7068 70.68% . 70 68 (70.68%) 48.93% 4893 48 93 (48.93% 86.11%. 8611 86.11% 86 (86.11%) 59.19%. 5919 59.19% 59 19 (59.19%) 20 3043 30 43 30.43% 1250 12 50 12.50% p=0.01, p001 p p=0.01 , 0 01 (p=0.01) highgrade grade p=0.008, p0008 p=0.008 008 (p=0.008) p=0.007, p0007 p=0.007 007 (p=0.007) p=0.03 p003 03 (p=0.03 survival conclusion 65.33 653 6 3 (65.33 455 4 5 45. 64.28 642 2 (64.28 95.66 956 9 (95.66 706 70.68 (70.68% 48.93 489 (48.93 861 86.11 8 (86.11% 591 59.19 (59.19% 304 30.43 125 12.50 p00 p=0.0 (p=0.01 p000 p=0.00 00 (p=0.008 (p=0.007 (p=0.0 65.3 (65.3 64.2 (64.2 95.6 (95.6 70.6 (70.68 48.9 (48.9 86.1 (86.11 59.1 (59.19 30.4 12.5 p0 p=0. (p=0.00 (p=0. 65. (65. 64. (64. 95. (95. 70. (70.6 48. (48. 86. (86.1 59. (59.1 30. 12. p=0 (p=0 (65 (64 (95 (70. (48 (86. (59. p= (p= (6 (9 (70 (4 (86 (59 (p ( (7 (8 (5

RESUMO Objetivos: Os objetivos do presente estudo foram avaliar o comportamento sedentário e os níveis de atividade física antes e durante da pandemia de COVID-19 em indivíduos saudáveis e com diagnóstico autorreportado de ansiedade e/ou depressão e identificar os facilitadores e barreiras para a prática de atividade física nessas populações. Métodos: Trata-se de uma pesquisa de corte transversal baseada em um questionário de autorrelato aplicado durante o período de pandemia da COVID-19. Resultados: Na amostra total (N = 1.285), a prevalência de comportamento sedentário (>8 horas/dia) aumentou em 25% durante o isolamento social. O isolamento social aumentou o tempo sedentário e diminuiu os níveis de atividade física em indivíduos saudáveis, com ansiedade e/ou depressão autorreportada. Nos dois grupos, os facilitadores mais prevalentes foram a atividade física supervisionada (antes da pandemia) e as atividades e equipamentos para a prática em casa (durante a pandemia). As barreiras mais prevalentes foram a falta de tempo para realizar atividades físicas (antes da pandemia) e os locais inacessíveis ou distantes para a prática (durante a pandemia). Conclusão: A pandemia de COVID-19 está relacionada a aumento do comportamento sedentário e redução dos níveis de atividade física. Mudanças significativas nas barreiras percebidas e facilitadores ao exercício foram observadas durante o período de isolamento social. Objetivos COVID19 COVID 19 COVID-1 eou populações Métodos Tratase Trata se COVID19. 19. Resultados N 1.285, 1285 1.285 , 1 285 1.285) >8 8 (> horas/dia horasdia horas dia 25 autorreportada grupos pandemia. . Conclusão COVID1 COVID- 128 1.28 28 > ( 2 12 1.2 1.

ABSTRACT Objectives: The objectives of the present study were to assess sedentary behavior and physical activity levels before and during the COVID-19 pandemic in healthy individuals and in those with self-reported diagnosis of anxiety and/or depression, and also identify facilitators and barriers to physical activity in these populations. Methods: This is a cross-sectional survey based on a self-report questionnaire applied during the COVID-19 pandemic period. Results: In the total sample (N = 1,285) the prevalence of sedentary behavior (>8 hours/day) increased by 25% during social isolation. Social isolation increased sedentary time and decreased physical activity levels in healthy individuals and in those with self-reported diagnosis of anxiety and/or depression. In both groups, the most prevalent facilitators were supervised physical activity (before the pandemic) and activities and equipment to practice at home (during the pandemic). The most prevalent barriers were the lack of time to perform physical activities (before the pandemic) and inaccessible or distance places to practice (during the pandemic). Conclusion: The COVID-19 pandemic is related to an increased sedentary behavior and reduced physical activity levels. Significant changes in perceived barriers and facilitators to exercise were observed during the social isolation period. Objectives COVID19 COVID 19 COVID-1 selfreported self reported andor depression populations Methods crosssectional cross sectional selfreport report period Results N 1,285 1285 1 285 >8 8 (> hours/day hoursday hours day 25 groups pandemic. . Conclusion COVID1 COVID- 1,28 128 28 > ( 2 1,2 12 1,

Abstract Objectives To assess alcohol use and perceived change in alcohol consumption (before and during the pandemic) in Brazilians during the COVID-19 pandemic, their correlates, and their associations with depressive, anxiety and co-occurring depressive and anxiety symptoms (D&A). Methods This is a cross-sectional study comprising 992 individuals in self-isolation. A self-report questionnaire was used to assess whether participants were drinking during self-isolation and whether they changed their drinking behavior (drinking less, more, or no change) from before to during the pandemic. D&A symptoms were assessed using the Beck Depression and Anxiety Inventories (BDI and BAI). Results A total of 68.5% of participants reported alcohol consumption during the pandemic, and 22.7% of these reported increased alcohol use. Smoking was positively associated with alcohol consumption during the pandemic. Alcohol consumption was associated with anxiety (OR = 1.40, 95%CI 1.06-1.85, p < 0.01) and D&A (OR = 1.38, 95%CI 1.02-1.87, p = 0.033) symptoms. Conclusions Drinking during self-isolation was prevalent and was associated with risk factors for alcohol use disorders. The long-term effects of high drinking rates and increased consumption should be proactively monitored and assessed. pandemic COVID19 COVID 19 COVID-1 correlates cooccurring co occurring D&A. DA . D (D&A) crosssectional cross sectional 99 selfisolation. selfisolation self isolation. isolation selfreport report less more BDI BAI. BAI BAI) 685 68 5 68.5 227 22 7 22.7 OR 140 1 40 1.40 95CI CI 95 1.061.85, 106185 1.06 1.85, 06 85 1.06-1.85 0.01 001 0 01 138 38 1.38 1.021.87, 102187 1.02 1.87, 02 87 1.02-1.87 0.033 0033 033 disorders longterm long term COVID1 COVID- (D&A 9 6 68. 2 22. 14 4 1.4 061 1.061.85 10618 106 1.0 185 1.85 8 1.06-1.8 0.0 00 13 3 1.3 021 1.021.87 10218 102 187 1.87 1.02-1.8 0.03 003 03 1. 1.061.8 1061 10 18 1.8 1.06-1. 0. 1.021.8 1021 1.02-1. 1.061. 1.06-1 1.021. 1.02-1 1.061 1.06- 1.021 1.02-

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: 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.

Resumo Acretismo placentário é uma condição caracterizada pela implantação anormal da placenta, que pode ser subdividida em três espectros de acordo com o seu grau de invasão: placenta acreta (ultrapassa a decídua basal e adere ao miométrio), placenta increta (penetra o miométrio) e placenta percreta (invasão da serosa uterina ou de tecidos/órgãos adjacentes). A incidência de acretismo placentário aumentou significativamente nas últimas décadas, principalmente em função da elevação das taxas de cesarianas, sendo este o seu principal fator de risco. A sua identificação pré-natal precisa permite um tratamento ideal com equipe multidisciplinar, minimizando significativamente a morbimortalidade materna. Os exames de escolha são a ultrassonografia e a ressonância magnética (RM), sendo a RM um método complementar indicado quando a avaliação ultrassonográfica é duvidosa, para pacientes com fatores de risco para acretismo placentário ou quando a placenta tem localização posterior. A RM é preferível também para avaliar invasão de órgãos adjacentes, oferecendo um campo de visão mais amplo, o que melhora o planejamento cirúrgico. Diversas características na RM são descritas no acretismo placentário, incluindo bandas hipointensas em T2 intraplacentárias, protuberância uterina anormal e heterogeneidade placentária. O conhecimento desses achados e a combinação de mais de um critério aumentam a confiabilidade do diagnóstico.

Abstract Placenta accreta spectrum disorders are characterized by abnormal adhesion of the placenta that can be subdivided into three categories according to degree of invasion: placenta accreta (passing through the decidua basalis and adhering to the myometrium); placenta increta (penetrating the myometrium); and placenta percreta (invading the uterine serosa or adjacent tissues or organs). The incidence of placenta accreta has increased significantly in recent decades, mainly because of an increase in the rates of cesarean section, which is its main risk factor. Accurate prenatal identification makes it possible to institute the ideal treatment with a multidisciplinary team, significantly minimizing maternal morbidity and mortality. The examinations of choice are ultrasound and magnetic resonance imaging (MRI). When the ultrasound evaluation is inconclusive, as well as when the patient has risk factors for the condition or the placenta is in a posterior location, MRI is indicated. In cases of placental invasion of the adjacent pelvic organs, MRI is also preferable because it provides a broader field of view, which improves surgical planning. Numerous features of placenta accreta spectrum disorders are discernible on MRI, including dark intraplacental bands, uterine bulging, and heterogeneous placenta. Knowledge of these findings and the combination of two or more of them increase confidence in the diagnosis.

Objective: Conduct a systematic review and meta-analysis to evaluate levels of anger among substance users compared to non-user controls and to analyze the possible association between anger and psychoactive substance use (PSU). Methods: The procedures of this review followed the Meta-Analyzes of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four electronic databases (MEDLINE, EMBASE, BIREME, PsycINFO) were searched. Results: Twelve studies were included in the meta-analysis; 10 used the State-Trait Anger Expression Inventory (STAXI) anger trait subscale and two used the Buss-Perry-Aggression Questionnaire (BPAQ) anger subscale. The sample included 2,294 users of psychoactive substances and 2,143 non-users, all male. The mean difference in anger scale scores between users and non-users was 2.151 (95%CI 1.166-3.134, p ≤ 0.00, inconsistency index [I2] = 98.83) standard deviations. Age and abstinence duration did not moderate the difference in anger between substance users and non-users. Conclusion: Users of psychoactive substances had elevated anger scores compared to non-users, which represents a high risk of relapse. It is suggested that PSU treatment programs include intensive anger management modules, focusing on factors such as dealing with daily stressors, family conflicts, frustrations, and problems.

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.