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1.
Alcohol ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38621495

RESUMO

BACKGROUND: Shortening telomere length (TL) is an important ageing marker associated with substance use disorder (SUD). However, the influence of psychiatric and clinical comorbidities and alcohol-related outcomes has not been much explored in the context of TL in individuals with alcohol use disorder (AUD) and may be a source of heterogeneity in AUD studies. Therefore, our aim was to investigate the influence of AUD, alcohol-related outcomes, and common psychiatric comorbidities on TL in men with AUD and healthy controls (HC). METHODS: Men with AUD (n=108, mean age=52.4, SD=8.6) were recruited in a detoxification unit, and HC (n=80, mean age=50.04, SD=9.1) from the blood bank, both located in Brazil. HC had no current or lifetime diagnosis of any substance use disorder. Psychiatric comorbidities were assessed using SCID-I. TL ratio was measured in triplicates using quantitative multiplex PCR. RESULTS: Telomere length did not differ between individuals with AUD and HC (p=0.073) or was associated with AUD-related outcomes, trauma, or clinical comorbidities. Individuals with externalizing disorders had longer TL when comparing with those with internalizing disorders (p=0.018) or without comorbidity (p=0.018). CONCLUSION: Our findings indicate that TL was influenced by the presence of psychiatric comorbidity rather than case or control status. These results were adjusted for potential confounders, such as age.

2.
Genet Mol Biol ; 46(3 Suppl 1): e20230139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38197733

RESUMO

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.

3.
Alcohol ; 111: 1-7, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37037287

RESUMO

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.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Cocaína Crack , Síndrome de Abstinência a Substâncias , Masculino , Humanos , Fator Neurotrófico Derivado do Encéfalo , Seguimentos , Etanol
4.
Trends Psychiatry Psychother ; 45: e20220567, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36889679

RESUMO

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.


Assuntos
Cocaína Crack , Transtornos Relacionados ao Uso de Substâncias , Adulto , Humanos , Masculino , Estudos Transversais , Cognição , Testes de Estado Mental e Demência , Etanol
5.
Trends Psychiatry Psychother ; 45: e20210401, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34898144

RESUMO

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.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína Crack , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Alta do Paciente , Pacientes Internados
6.
Trends psychiatry psychother. (Impr.) ; 45: e20210401, 2023. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1442238

RESUMO

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.

7.
Trends psychiatry psychother. (Impr.) ; 45: e20220567, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1509228

RESUMO

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.

8.
Clin. biomed. res ; 43(1): 95-99, 2023.
Artigo em Português | LILACS | ID: biblio-1436279

RESUMO

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.


Assuntos
Humanos , Masculino , Adolescente , Adulto , Pessoa de Meia-Idade , História do Século XVIII , Adulto Jovem , Transtornos Relacionados ao Uso de Álcool/complicações , Infecções por HIV/prevenção & controle , Fatores de Risco
9.
Transl Psychiatry ; 12(1): 470, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36347838

RESUMO

Although reducing criminal outcomes in individuals with mental illness have long been a priority for governments worldwide, there is still a lack of objective and highly accurate tools that can predict these events at an individual level. Predictive machine learning models may provide a unique opportunity to identify those at the highest risk of criminal activity and facilitate personalized rehabilitation strategies. Therefore, this systematic review and meta-analysis aims to describe the diagnostic accuracy of studies using machine learning techniques to predict criminal and violent outcomes in psychiatry. We performed meta-analyses using the mada, meta, and dmetatools packages in R to predict criminal and violent outcomes in psychiatric patients (n = 2428) (Registration Number: CRD42019127169) by searching PubMed, Scopus, and Web of Science for articles published in any language up to April 2022. Twenty studies were included in the systematic review. Overall, studies used single-nucleotide polymorphisms, text analysis, psychometric scales, hospital records, and resting-state regional cerebral blood flow to build predictive models. Of the studies described in the systematic review, nine were included in the present meta-analysis. The area under the curve (AUC) for predicting violent and criminal outcomes in psychiatry was 0.816 (95% Confidence Interval (CI): 70.57-88.15), with a partial AUC of 0.773, and average sensitivity of 73.33% (95% CI: 64.09-79.63), and average specificity of 72.90% (95% CI: 63.98-79.66), respectively. Furthermore, the pooled accuracy across models was 71.45% (95% CI: 60.88-83.86), with a tau squared (τ2) of 0.0424 (95% CI: 0.0184-0.1553). Based on available evidence, we suggest that prospective models include evidence-based risk factors identified in prior actuarial models. Moreover, there is a need for a greater emphasis on identifying biological features and incorporating novel variables which have not been explored in prior literature. Furthermore, available models remain preliminary, and prospective validation with independent datasets, and across cultures, will be required prior to clinical implementation. Nonetheless, predictive machine learning models hold promise in providing clinicians and researchers with actionable tools to improve how we prevent, detect, or intervene in relevant crime and violent-related outcomes in psychiatry.


Assuntos
Criminosos , Transtornos Mentais , Psiquiatria , Humanos , Agressão , Transtornos Mentais/diagnóstico , Área Sob a Curva
10.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 44(4): 416-419, July-Aug. 2022. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1394065

RESUMO

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.

11.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 44(4): 441-448, July-Aug. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1394079

RESUMO

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.

12.
Braz J Psychiatry ; 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35739064

RESUMO

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.

13.
Braz J Psychiatry ; 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35751594

RESUMO

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.

14.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 44(1): 103-110, Jan.-Feb. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1360178

RESUMO

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.

15.
Braz J Psychiatry ; 44(1): 103-110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33605366

RESUMO

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.


Assuntos
Ira , Transtornos Relacionados ao Uso de Substâncias , Agressão , Humanos , Masculino , Inventário de Personalidade , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários
17.
Trends Psychiatry Psychother ; 42(2): 153-160, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32696891

RESUMO

Introduction Drug-related crimes, especially drug trafficking, account for a large part of incarcerations not only in Brazil, but also worldwide. It is not clear whether the change in the drug law has contributed to the increase in the number of drug trafficking prisoners. Few studies have investigated gender differences and the growth of drug trafficking offenses in the Brazilian southern state of Rio Grande do Sul. Objective To investigate the growth of the prison population in the state of Rio Grande do Sul, emphasizing incarcerations for drug trafficking and gender differences. Method This was an ecological study using secondary data collected from official databases of the Brazilian National Penitentiary Department (Departamento Penitenciário [DEPEN]), affiliated with the Brazilian Ministry of Justice. Results Between 2006 and 2015, incarcerations increased by 27% (25% men, 83% women). Incarcerations for drug trafficking accounted for 11% of total arrests in 2006 (11% men, 20% women) and 45% in 2015 (47% men, 91% women), corresponding to an increase of 427% (415% among men, 723% among women). Conclusions Imprisonment for drug trafficking has increased considerably, especially among women. This may be due to factors such as: increase of drug trafficking, increase in the numbers of gangs in the state, and changes in the Brazilian drug law. These results highlight an emerging challenge in public health from the perspective of human rights and gender.


Assuntos
Direito Penal , Tráfico de Drogas/estatística & dados numéricos , Legislação de Medicamentos , Prisioneiros/estatística & dados numéricos , Adulto , Brasil , Feminino , Humanos , Masculino , Saúde Pública , Fatores Sexuais
18.
Neuromolecular Med ; 22(3): 384-390, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152934

RESUMO

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.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/genética , Cocaína Crack/efeitos adversos , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Receptores Nicotínicos/genética , Adulto , Alelos , Estudos de Casos e Controles , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Simulação por Computador , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos/genética , Humanos , Masculino , Risco , Relação Estrutura-Atividade , Adulto Jovem
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