A hierarchical analysis of associated factors to lifetime suicide attempts in alcohol use disorder.

BACKGROUND: Substance use is strongly associated with suicide attempts throughout life. We aimed to investigate the prevalence of suicide attempts (SA) and associated factors in life in patients with Alcohol Use Disorder (AUD). METHODS: The sample consisted of 424 men with AUD who underwent treatment at the Addiction Psychiatry Unit of the Hospital de Clínicas de Porto Alegre. The clinical evaluation included the Addiction Severity Index, the Childhood Trauma Questionnaire, the Barratt Impulsiveness Scale, and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders. Variables that showed p-value < 0.05 in the bivariate analyses were included in a hierarchical regression model with robust variance to investigate associations with SA in life via estimation of adjusted Prevalence Ratios (PR). RESULTS: The lifetime prevalence of SA among alcohol users was 36.6%. Patients with childhood maltreatment, borderline personality disorder, and higher impulsivity scores had a higher lifetime prevalence of SA. CONCLUSION: Our findings indicate that male inpatient alcoholics present an important prevalence of SA. The study also corroborates the relationship between maltreatment, impulsivity, and borderline personality disorder with SA among inpatients in treatment for AUD.

Global DNA methylation patterns in Alcohol Use Disorder.

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.

Cocaine-use disorder and childhood maltreatment are associated with the activation of neutrophils and increased inflammation.

BACKGROUND: Cocaine-use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of neutrophil extracellular traps (NETs) and related intracellular signalling. We also investigated the role of early life stress in inflammatory profiles. METHODS: Blood samples, clinical data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HCs). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular reactive oxygen species (ROS) generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry. RESULTS: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1ß, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared to HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signalling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation. CONCLUSION: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.

Serum BDNF levels increase during early drug withdrawal in alcohol and crack cocaine addiction.

Brain-derived neurotrophic factor (BDNF) is involved in several drug-induced brain neuroadaptations. The impact of withdrawal from substances that have different neurological mechanisms on BDNF levels is unclear. Our goal was to compare serum BDNF levels in inpatients with alcohol or crack cocaine use disorders during the early withdrawal period, and to evaluate the association with substance-related outcomes. We performed a follow-up study with 101 men under detoxification treatment (drug preference: alcohol [n = 37] and crack cocaine [n = 64]). Blood samples were collected on the 1st and 15th days of hospitalization to measure serum BDNF levels. Serum BDNF levels increased during the early stage of withdrawal (28.2 ± 10.0 vs. 32.6 ± 13.3, p < 0.001), similarly in individuals with alcohol and crack cocaine use. In the alcohol group, BDNF levels on the 15th day of hospitalization were negatively correlated with age (r = -0.394, p = 0.023). Delta BDNF levels were also negatively correlated with BDNF on the 1st day of hospitalization (p = 0.011). No significant correlation was found regarding substance-related outcomes. This is the first study to compare BDNF levels in alcohol and crack cocaine users undergoing similar treatment conditions. These findings could be related to clinical improvement after abstinence or even to drug withdrawal itself, decreasing neuronal injury. Furthermore, age may be a crucial factor, hindering the recovery of neuroplasticity in alcohol users.

Assessment of cognitive functioning using the Mini Mental State Examination in men with Alcohol and Crack Cocaine Use Disorder.

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.

Early discharge predictors among inpatients crack cocaine users.

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.

Early discharge predictors among inpatient crack cocaine users

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.

Assessment of cognitive functioning using the Mini Mental State Examination in men with alcohol and crack cocaine use disorder

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.

Fatores associados à exposição ao HIV em usuários de álcool / Factors associated with HIV exposure in alcohol users

Introdução: A prevalência de HIV é maior em Porto Alegre comparada ao restante do país. O abuso de álcool afeta o juízo crítico, sendo associado a comportamentos de risco que podem levar à contaminação pelo HIV. Objetiva-se analisar fatores associados à exposição ao HIV em alcoolistas com práticas sexuais de risco comparando com aqueles que se previnem.Métodos: Estudo transversal com 126 homens alcoolistas (HIV negativo), divididos em 2 grupos: Exposto Sexual (n = 42) e Pouco Exposto Sexual (n = 84), considerando uso de preservativo e número de parceiros sexuais.Resultados: A maioria dos sujeitos do grupo Exposto Sexual era solteiro, sem ocupação laboral, com histórico de moradia de rua e de relação com profissional do sexo, apresentavam maior preocupação com infecção por HIV (p < 0,05).Conclusão: Sugere-se o desenvolvimento e monitoramento de intervenções preventivas específicas, considerando as características do abuso de álcool e seu papel na transmissão do HIV.

Introduction: The HIV prevalence is higher in Porto Alegre compared to other capitals in Brazil. Alcohol abuse affects critical judgment, being associated with risky behaviors that can lead to HIV infection. Aim:To analyze factors associated with exposure to HIV in alcohol users, comparing those with risky sexual practices and those who use prevention methods.Methods: Cross-sectional study with 126 male alcohol users (HIV negative), divided into 2 groups: Sexually Exposed (n = 42) and Less Sexually Exposed (n = 84), considering condom use and number of sexual partners.Results: Most subjects in the Sexually Exposed group were single, without a job, with a history of homelessness and a relationship with a sexual worker, and were more concerned about HIV infection (p < 0.05).Conclusion: The development and monitoring of specific preventive interventions is suggested, considering the characteristics of alcohol abuse and its role in HIV transmission.

Childhood trauma subtypes may influence the pattern of substance use and preferential substance in men with alcohol and/or crack-cocaine addiction

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.

Prevalence of suicide in cocaine users accessing health services: a systematic review and meta-analysis

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.

Childhood trauma subtypes may influence the pattern of substance use and preferential substance in men with alcohol and/or crack-cocaine addiction.

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.

Prevalence of suicide in cocaine users accessing health services: a systematic review and meta-analysis.

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.

Oxytocin Receptor Exon III Methylation in the Umbilical Cord Blood of Newborns With Prenatal Exposure to Crack Cocaine.

BACKGROUND: Prenatal cocaine exposure (PCE) is associated with behavioral, cognitive, and social consequences in children that might persist into later development. However, there are still few data concerning epigenetic mechanisms associated with the effects of gestational cocaine exposure, particularly in human newborns. AIMS: We investigated the effects of PCE on DNA methylation patterns of the Oxytocin Receptor (OXTR) gene in the umbilical cord blood (UCB). The relationship between UCB DNA methylation levels and the severity of the mother's cocaine use during pregnancy was also evaluated. METHODS: In this cross-sectional study, 28 UCB samples of newborns with a history of crack cocaine exposure in utero and 30 UCB samples of non-exposed newborns (NEC) were compared for DNA methylation levels at two genomic loci located in exon III of the OXTR gene (OXTR1 and OXTR2) through pyrosequencing. Maternal psychopathology was investigated using the Mini International Neuropsychiatric Interview, and substance use characteristics and addiction severity were assessed using the Smoking and Substance Involvement Screening Test (ASSIST). RESULTS: No differences between newborns with a history of PCE and NEC were observed in OXTR1 or OXTR2 DNA methylation levels. However, regression analyses showed that maternal addiction severity for crack cocaine use predicted OXTR1 DNA methylation in newborns. CONCLUSION: These data suggest that OXTR methylation levels in the UCB of children are affected by the severity of maternal crack cocaine usage. Larger studies are likely to detect specific changes in DNA methylation relevant to the consequences of PCE.

Drug use and driving behaviors among drivers with and without alcohol-related infractions.

INTRODUCTION: Brazil is one of the countries with the highest rates of alcohol-related traffic infractions, but little is known about the profile of the drivers who commit them. Identifying the characteristics of impaired drivers is essential for planning preventive actions. OBJECTIVE: To compare drug use and driving behavior profiles of drivers with and without alcohol-related infractions. METHODS: 178 drivers stopped at routine roadblocks were assessed by traffic agents who conducted standard roadblock procedures (document verification; request of a breathalyzer test [BT]). Drug use and driving behavior data were collected through semi-structured interviews. Subjects were divided into three groups: drivers who refused the BT (RDs, n = 72), drivers who tested positive on the BT (PDs, n = 34), and drivers who had committed other infractions (ODs, n = 72). RESULTS: The proportion of alcohol use in the last year was higher among RDs (100%) than in the PD and OD groups (97.1% and 72.2% respectively, p < 0.001). Lifetime prevalence of cannabis and cocaine use for the overall sample was 44.3% and 18.2%, respectively. Fewer individuals in the OD group (31.5%) reported having been stopped at roadblocks in the previous year compared to the PDs (55.9%) and RDs (48.6%, p = 0.03). However, a higher proportion of RDs reported drunk driving in the same period (87.5%; PD 69.7%; OD 26.9%; p < 0.001). CONCLUSION: Essential differences among groups were observed. RDs had a higher proportion of alcohol use and drunk driving in the previous year; drivers who fit into this particular group may be unresponsive or less responsive to social deterrence and enforcement actions.

Modulation of neuropeptide Y levels is impaired in crack withdrawal patients.

Introduction The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has a key role in drug addiction susceptibility. In addition to the well-known relationship between cortisol and the HPA axis, other molecules are involved with stress response and could modify the HPA activation, such as the neuropeptide Y (NPY), which has anxiolytic proprieties. There are few studies evaluating the effect of NPY levels on addiction, especially in crack cocaine dependence. Objective To evaluate NPY in crack users during early withdrawal to determine its relationship with drug use and cortisol levels. Methods We analyzed 25 male inpatient crack users. Serum NPY levels were measured at admission and discharge (mean of 24 days). Morning salivary cortisol was measured at admission. Results Serum NPY levels at admission and discharge were very similar. Lower NPY levels at discharge were associated with higher lifetime crack use. Also, a negative correlation was found between morning cortisol and delta NPY (NPY discharge - NPY admission). Conclusion These preliminary findings indicate that crack use influences the modulation of NPY levels and modifies stress response. The NPY pathway may play an important role in the pathophysiology of crack addiction, and the anxiolytic effect of NPY may be impaired in crack users. Future studies should consider NPY as a measurable indicator of the biological state in addiction.

Association of CHRNA5 Gene Variants with Crack Cocaine Addiction.

Genome-wide studies provide increasing evidence of association of genetic variants with different behaviors. However, there is a growing need for replication and subsequent characterization of specific findings. In this sense, the CHRNA5 gene has been associated with nicotine (with genome-wide significance), alcohol and cocaine addictions. So far, this gene has not been evaluated in smoked (crack) cocaine. We aimed to analyze the influence of CHRNA5 variants in crack addiction susceptibility and severity. The sample includes 300 crack-addicted patients and 769 non-addicted individuals. The CHRNA5 SNPs evaluated were rs588765, rs16969968, and rs514743. Homozygosity for rs16969968 and rs588765 major alleles was nominally associated with a risk to crack addiction (GG, P = 0.032; CC, P = 0.036, respectively). Haplotype analyses reveal significant associations (rs588765|rs16969968|rs514743 pglobal-corrected = 7.66 × 10-5) and suggest a substantial role for rs16969968. These findings corroborate previous reports in cocaine addiction-in line with the expected effects of cocaine in the cholinergic system-and in the opposite direction of significant GWAS findings for nicotine addiction susceptibility. These results are strengthened by the first report of an association of rs588765 with crack addiction and by the haplotype findings. In summary, our study highlights the relevance of the α5 subunit on crack cocaine addiction, replicating previous results relating CHRNA5 with the genetics and pathophysiology of addiction of different drugs.

Increased cortisol levels are associated with low treatment retention in crack cocaine users.

BACKGROUND: Dysregulation of the hypothalamic-pituitaryadrenal (HPA) axis has been associated with craving and early relapse among individuals with substance use disorders. However, no association has been postulated regarding treatment retention and prognosis in crack cocaine users. OBJECTIVE: Our aim was to investigate the association between morning salivary cortisol levels and treatment retention in crack cocaine users. METHODS: 44 male crack cocaine users were recruited from a detoxification unit. Saliva collection was performed in the morning of the second treatment day. Substance use profile was assessed using the Addiction Severity Index. RESULTS: The median length of stay in inpatient treatment was 7 days (IQR 3-16). Treatment retention was associated with cortisol levels (r = -0.324; p = 0.032), especially in the group with positive family history. Moreover, treatment retention was correlated with age (r = 0.333, p = 0.027), and number of days of tobacco use (r = 0.332, p = 0.028) and crack use (r = 0.327, p = 0.031). A Cox regression model was performed and showed that inpatients with above normal cortisol levels (≥0.69 µg/dL) presented a worse prognostic related to treatment retention (HR = 2.39, CI95% 1.1-5.1, p = 0.024). CONCLUSION: Several factors could contribute to increased cortisol levels in these patients, e.g. craving, dysregulation of the HPA axis, chronic drug use, stress due to confinement, and substance abstinence. Nevertheless, our findings could guide further studies about new biomarkers in crack cocaine use disorder, since HPA axis dysregulation at the time of treatment admittance may be a prognostic marker for treatment retention.