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HIV risk behaviors among returnee male migrant workers in Nepal
Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
Association between ␣-1 adrenergic receptor (ADRA1A) genotype and subjective cocaine effect in cocaine-dependent individuals Daryl Shorter 1,2 , David A. Nielsen 1,2 , Thomas F. Newton 1,2 , Richard De La Garza II 1,2 , T.R. Kosten 1,2 1
Michael E. DeBakey VA Medical Center, Houston, TX, United States 2 Department of Psychiatry and Behavioral Science, Baylor College of Medicine, Houston, TX, United States Aims: We examined whether a functional variant of the ADRA1A gene enhances the subjective effects of cocaine in a group of cocaine dependent individuals. Methods: This study is a within-subject, double blind, placebo-controlled inpatient human laboratory evaluation of 46 non-treatment seeking cocaine dependent (DSM-IV) subjects, aged 18–55 yr. Participants received both placebo (saline, IV) and cocaine (40 mg, IV), and subjective responses were assessed 15 min prior to receiving cocaine and at 5-min intervals for 20 min following cocaine administration. We then genotyped the rs1048101 ADRA1A variant and evaluated whether the Cys to Arg substitution at codon 347 in exon 2 (Cys347Arg) was associated with the subject’s rating of cocaine effect. Results: Nineteen (41%) subjects were found to have the major allele CC genotype, and 27 (59%) carried at least one T allele of rs1048101 (TT or TC genotype). Significant between group differences in subjective effects were observed for “Cocaine Desire” (p < 0.05) and for “Cocaine Liking” (p < 0.05), with those in the CC genotype reporting higher ratings of drug desire and drug liking. In addition, although there was no statistically significant difference between groups in regards to baseline depression score, the CC group also reported higher depression scores after receiving cocaine infusion (p = 0.03). Conclusions: The CC genotype of ADRA1 was found to be associated with elevated ratings of cocaine desire and liking. This study indicates that ADRA1A genotype could be used to identify a subset of individuals for whom cocaine may be more rewarding. Financial support: Funding for this study was provided by NIDA Grant 5 P50 DA018197-07 (TRK). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.575 HIV risk behaviors among returnee male migrant workers in Nepal R. Shrestha, Michael Copenhaver Allied Health Sciences, University of Connecticut, Storrs, CT, United States Aims: Seasonal migration of Nepali male workers to India is common in Nepal. Unsafe sexual activities and drug use behaviors of these migrants in India and after returning to Nepal, has led to a high HIV prevalence among this sub-group. This study was designed to explore consequential risk behaviors that contribute to migrant workers’ vulnerability to HIV infection and transmission. Methods: We performed a systematic review of literature focused on “HIV risk behaviors of male labor migrants”. Records were collected from electronic databases, web-based searches, and national and international reports. Results: HIV prevalence in Nepal, though it decreased from 8.5% in 2002 to 1.1% in 2008, is still very high among male migrant labor workers and rates are rapidly trending higher in association with increased high-risk behaviors in this group. A startling 41% of all HIV
e207
infections in Nepal are among male migrant workers. This review found that migrant workers commonly exhibit HIV risk behaviors such as having multiple sex partners, inconsistent condom use, unsafe drug use, and alcohol use disorders. Furthermore, we found that they have substantial deficits in knowledge of HIV/STIs, and safe sex and safe drug use skills. Conclusions: Our findings suggest that migrant labor workers are at extraordinary risk for acquiring and transmitting HIV infection because of higher prevalence of HIV risk sexual and drug use behaviors. This review suggests the need for a comprehensive HIV program addressing safe sex and drug use habits directed toward migrants labor workers in order to reduce the risk of spreading HIV. Financial support: University of Connecticut, College of Liberal Art and Sciences (Christine N. Witzel Award). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.576 Attenuation of depressive symptoms associated with MTHFR during a cocaine vaccine trial Timothy R. Shutter 1,2 , Daryl Shorter 1,2 , David A. Nielsen 1,2 , T.R. Kosten 1,2 1
Psychiatry and Behavioral Science, Baylor College of Medicine, Houston, TX, United States 2 Psychiatry and Behavioral Science, MED-VAMC, Houston, TX, United States Aims: This study assessed whether a cocaine vaccine that reduced cocaine use interacted with a genetic variant of the methylenetetrahydrofolate reductase (MTHFR) gene to reduce depression levels in cocaine and opiate dependent patients. Methods: This 14-week randomized clinical trial assessed depression scores using a modified version of the Center for Epidemiological Studies Depression scale (CES-D) and cocaine positive urine percentages in 64 cocaine and opioid codependent subjects on methadone. We genotyped the rs1801133 MTHFR variant and evaluated whether the C to T mutation at the C677T polymorphic site was associated with the subject’s depression and cocaine use. Results: Depression scores for the TT genotype patients were elevated at 2.7 during the 4-week baseline and decreased to 0.4 for the TT vaccinated group, while depression scores remained elevated for the TT placebo group. The CC and CT genotypes group were 0.8 for the vaccine and 1.4 for the placebo group at baseline, and remained low throughout the study. Cocaine positive urines decreased from 81% to 45% for the TT vaccine group and remained near baseline levels of 60% for the TT placebo group. The change in CES-D scores was positively correlated with the change in cocaine-free urines for the TT patients (r = 27.1), and co-varying for the change in cocaine-free urines eliminated the association of increased depression symptoms with vaccine treatment and the MTHFR polymorphism. Conclusions: The TT genotype of MTHFR was found to be associated with elevated depressive symptoms, and these symptoms dropped with a reduction in cocaine use suggesting that elevated homocysteine levels from cocaine use with the TT variant may produce depressive symptoms that resolve with reduced cocaine use. Financial support: NIH/NIDA r0115477 (TK), for DN through MD Anderson’s Cancer Center Support Grant DA026120 NIH/NIDA DA026120, the Veterans Health Administration, and the Toomim Family Fund. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.577
Association between ␣-1 adrenergic receptor (ADRA1A) genotype and subjective cocaine effect in cocaine-dependent individuals Daryl Shorter 1,2 , David A. Nielsen 1,2 , Thomas F. Newton 1,2 , Richard De La Garza II 1,2 , T.R. Kosten 1,2 1
Michael E. DeBakey VA Medical Center, Houston, TX, United States 2 Department of Psychiatry and Behavioral Science, Baylor College of Medicine, Houston, TX, United States Aims: We examined whether a functional variant of the ADRA1A gene enhances the subjective effects of cocaine in a group of cocaine dependent individuals. Methods: This study is a within-subject, double blind, placebo-controlled inpatient human laboratory evaluation of 46 non-treatment seeking cocaine dependent (DSM-IV) subjects, aged 18–55 yr. Participants received both placebo (saline, IV) and cocaine (40 mg, IV), and subjective responses were assessed 15 min prior to receiving cocaine and at 5-min intervals for 20 min following cocaine administration. We then genotyped the rs1048101 ADRA1A variant and evaluated whether the Cys to Arg substitution at codon 347 in exon 2 (Cys347Arg) was associated with the subject’s rating of cocaine effect. Results: Nineteen (41%) subjects were found to have the major allele CC genotype, and 27 (59%) carried at least one T allele of rs1048101 (TT or TC genotype). Significant between group differences in subjective effects were observed for “Cocaine Desire” (p < 0.05) and for “Cocaine Liking” (p < 0.05), with those in the CC genotype reporting higher ratings of drug desire and drug liking. In addition, although there was no statistically significant difference between groups in regards to baseline depression score, the CC group also reported higher depression scores after receiving cocaine infusion (p = 0.03). Conclusions: The CC genotype of ADRA1 was found to be associated with elevated ratings of cocaine desire and liking. This study indicates that ADRA1A genotype could be used to identify a subset of individuals for whom cocaine may be more rewarding. Financial support: Funding for this study was provided by NIDA Grant 5 P50 DA018197-07 (TRK). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.575 HIV risk behaviors among returnee male migrant workers in Nepal R. Shrestha, Michael Copenhaver Allied Health Sciences, University of Connecticut, Storrs, CT, United States Aims: Seasonal migration of Nepali male workers to India is common in Nepal. Unsafe sexual activities and drug use behaviors of these migrants in India and after returning to Nepal, has led to a high HIV prevalence among this sub-group. This study was designed to explore consequential risk behaviors that contribute to migrant workers’ vulnerability to HIV infection and transmission. Methods: We performed a systematic review of literature focused on “HIV risk behaviors of male labor migrants”. Records were collected from electronic databases, web-based searches, and national and international reports. Results: HIV prevalence in Nepal, though it decreased from 8.5% in 2002 to 1.1% in 2008, is still very high among male migrant labor workers and rates are rapidly trending higher in association with increased high-risk behaviors in this group. A startling 41% of all HIV
e207
infections in Nepal are among male migrant workers. This review found that migrant workers commonly exhibit HIV risk behaviors such as having multiple sex partners, inconsistent condom use, unsafe drug use, and alcohol use disorders. Furthermore, we found that they have substantial deficits in knowledge of HIV/STIs, and safe sex and safe drug use skills. Conclusions: Our findings suggest that migrant labor workers are at extraordinary risk for acquiring and transmitting HIV infection because of higher prevalence of HIV risk sexual and drug use behaviors. This review suggests the need for a comprehensive HIV program addressing safe sex and drug use habits directed toward migrants labor workers in order to reduce the risk of spreading HIV. Financial support: University of Connecticut, College of Liberal Art and Sciences (Christine N. Witzel Award). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.576 Attenuation of depressive symptoms associated with MTHFR during a cocaine vaccine trial Timothy R. Shutter 1,2 , Daryl Shorter 1,2 , David A. Nielsen 1,2 , T.R. Kosten 1,2 1
Psychiatry and Behavioral Science, Baylor College of Medicine, Houston, TX, United States 2 Psychiatry and Behavioral Science, MED-VAMC, Houston, TX, United States Aims: This study assessed whether a cocaine vaccine that reduced cocaine use interacted with a genetic variant of the methylenetetrahydrofolate reductase (MTHFR) gene to reduce depression levels in cocaine and opiate dependent patients. Methods: This 14-week randomized clinical trial assessed depression scores using a modified version of the Center for Epidemiological Studies Depression scale (CES-D) and cocaine positive urine percentages in 64 cocaine and opioid codependent subjects on methadone. We genotyped the rs1801133 MTHFR variant and evaluated whether the C to T mutation at the C677T polymorphic site was associated with the subject’s depression and cocaine use. Results: Depression scores for the TT genotype patients were elevated at 2.7 during the 4-week baseline and decreased to 0.4 for the TT vaccinated group, while depression scores remained elevated for the TT placebo group. The CC and CT genotypes group were 0.8 for the vaccine and 1.4 for the placebo group at baseline, and remained low throughout the study. Cocaine positive urines decreased from 81% to 45% for the TT vaccine group and remained near baseline levels of 60% for the TT placebo group. The change in CES-D scores was positively correlated with the change in cocaine-free urines for the TT patients (r = 27.1), and co-varying for the change in cocaine-free urines eliminated the association of increased depression symptoms with vaccine treatment and the MTHFR polymorphism. Conclusions: The TT genotype of MTHFR was found to be associated with elevated depressive symptoms, and these symptoms dropped with a reduction in cocaine use suggesting that elevated homocysteine levels from cocaine use with the TT variant may produce depressive symptoms that resolve with reduced cocaine use. Financial support: NIH/NIDA r0115477 (TK), for DN through MD Anderson’s Cancer Center Support Grant DA026120 NIH/NIDA DA026120, the Veterans Health Administration, and the Toomim Family Fund. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.577