Susceptibility loci for heroin and cocaine addiction in the serotonergic and adrenergic pathways in populations of different ancestry

Levran, Orna; Peles, Einat; Randesi, Matthew; Rosa, Joel Correa da; Ott, Jürg; Rotrosen, John; Adelson, Miriam; Kreek, Mary Jeanne

doi:10.2217/pgs.15.86

Cited by 15 publications

(8 citation statements)

References 74 publications

(86 reference statements)

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“…This was an observational study, with consecutively ascertained adult volunteers who were examined in an outpatient research hospital setting, in the New York City area. This cohort was originally recruited and ascertained as part of genetic association studies of SUD ( 40 – 42 ).…”

Section: Methodsmentioning

confidence: 99%

Non-medical Cannabis Self-Exposure as a Dimensional Predictor of Opioid Dependence Diagnosis: A Propensity Score Matched Analysis

et al. 2018

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Background: The impact of increasing non-medical cannabis use on vulnerability to develop opioid use disorders has received considerable attention, with contrasting findings. A dimensional analysis of self-exposure to cannabis and other drugs, in individuals with and without opioid dependence (OD) diagnoses, may clarify this issue.Objective: To examine the age of onset of maximal self-exposure to cannabis, alcohol, cocaine, and heroin, in volunteers diagnosed with OD, using a rapidly administered instrument (the KMSK scales). To then determine whether maximal self-exposure to cannabis, alcohol, and cocaine is a dimensional predictor of odds of OD diagnoses.Methods: This outpatient observational study examined maximal self-exposure to these drugs, in volunteers diagnosed with DSM-IV OD or other drug diagnoses, and normal volunteers. In order to focus more directly on opioid dependence diagnosis as the outcome, volunteers who had cocaine dependence diagnoses were excluded. Male and female adults of diverse ethnicity were consecutively ascertained from the community, and from local drug treatment programs, in 2002–2013 (n = 574, of whom n = 94 had OD diagnoses). The age of onset of maximal self-exposure of these drugs was examined. After propensity score matching for age at ascertainment, gender, and ethnicity, a multiple logistic regression examined how increasing self-exposure to non-medical cannabis, alcohol and cocaine affected odds of OD diagnoses.Results: Volunteers with OD diagnoses had the onset of heaviest use of cannabis in the approximate transition between adolescence and adulthood (mean age = 18.9 years), and onset of heaviest use of alcohol soon thereafter (mean age = 20.1 years). Onset of heaviest use of heroin and cocaine was detected later in the lifespan (mean ages = 24.7 and 25.3 years, respectively). After propensity score matching for demographic variables, we found that the maximal self-exposure to cannabis and cocaine, but not to alcohol, was greater in volunteers with OD diagnoses, than in those without this diagnosis. Also, a multiple logistic regression detected that increasing self-exposure to cannabis and cocaine, but not alcohol, was a positive predictor of OD diagnosis.Conclusions/Importance: Increasing self-exposure to non-medical cannabis, as measured with a rapid dimensional instrument, was a predictor of greater odds of opioid dependence diagnosis, in propensity score-matched samples.

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Section: Methodsmentioning

confidence: 99%

Non-medical Cannabis Self-Exposure as a Dimensional Predictor of Opioid Dependence Diagnosis: A Propensity Score Matched Analysis

et al. 2018

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“…However, the findings were contradictory to those of the study conducted by Samochowiec et al (2002) [35] in Berlin, Germany, which showed that SLC6A2 (G1287A Sau96I-RFLP) is unlikely to be involved in alcohol susceptibility and severe alcohol withdrawal. Another study by Levran et al (2015) [36] in a European and Middle Eastern subgroup showed that there is a possible association between the SLC6A2 genotype with opioid and cocaine dependence with two SNPs from SLC6A2 gene ( rs10521329 and rs3785155). Nevertheless, no association between SNPs rs3785157 with ATS and opioid dependence was established in our study indicating that the association is ethnic-specific.…”

Section: Discussionmentioning

confidence: 99%

Influence of dopaminergic system gene polymorphisms on mixed amphetamine-type stimulants and opioid dependence in Malaysian Malays

Bakar

Deeza-Syafiqah

Ahmad

et al. 2019

Egypt J Med Hum Genet

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Background: The dopaminergic pathways have previously been reported to be involved in drug dependence. The candidate gene involved in the dopaminergic function has been associated with substance abuse. Objective: The objective of the study is to investigate the possible association between dopaminergic system gene polymorphisms with mixed amphetamine-type stimulants and opioid dependence in Malaysian Malays. The study has never been done anywhere else, due to its unique population of study subjects. Subjects and methods In this study, genetic polymorphisms of dopamine D2 receptor (DRD2) dopamine transporter (SLC6A3), dopamine beta-hydroxylase (DβH), and norepinephrine transporter (SLC6A2) in Malay males (n = 70) having mixed amphetamine-type stimulant (ATS) and opioid dependence were compared with those in control subjects (n = 87). DNA was extracted from leucocytes followed by single nucleotide polymorphism (SNP) determination using PCR-RFLP. The association of the gene with drug dependency was analyzed using chi-squared tests. Results: There was a significant difference between the genotype (χ 2 = 10.048, p < 0.01) and allele frequency (χ 2 = 14.039, p = 0.000) of the DRD2 rs1800497 gene in the drug dependence group as compared to the control. There was also a significant difference in DβH rs1611115 at the allelic (χ 2 = 4.483, p = 0.034) but not at genotypic levels (χ 2 = 7.572, p = 0.23) in both control and drug dependence groups. There was an association for SLC6A3 rs27072 with drug dependence at the genotypic level (χ 2 = 7.006, p = 0.030) although no significant difference exist at the allelic level (χ 2 = 2.091, p = 0.148). No significant difference was observed in SLC6A2 rs3785157 genes polymorphism at both genotype and allelic level in control and drug dependence group respectively (χ 2 = 0.94, p = 0.954) (χ 2 = 0.29, p = 0.865) indicating that these polymorphisms do not affect drug dependence. Conclusion: Our study suggests that DRD2 rs1800497, DβH rs1611115, and SLC6A3 rs27072 but not SLC6A2 rs3785157 are associated with drug-dependent behavior among Malaysian Malays.

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“…We further stratified all participants (cases or controls) by the presence of depression diagnosis. This is a secondary analysis of participants systematically ascertained for genetic association studies …”

Section: Methodsmentioning

confidence: 99%

Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

et al. 2017

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Background and Objectives Addictions to heroin or to cocaine are associated with substantial psychiatric comorbidity, including depression. Poly-drug self-exposure (e.g., to heroin, cocaine, cannabis or alcohol) is also common, and may further affect depression comorbidity. Methods This case-control study examined the relationship of exposure to the above drugs and depression comorbidity. Participants were recruited from methadone maintenance clinics, and from the community. Adult male and female participants (n=1,201) were ascertained consecutively by experienced licensed clinicians. The instruments used were the SCID-I, and Kreek-McHugh-Schluger-Kellogg (KMSK) scales, which provide a rapid dimensional measure of maximal lifetime self-exposure to each of the above drugs. This measure ranges from no exposure to high unit dose, high frequency, and long duration of exposure. Results A multiple logistic regression with stepwise variable selection revealed that increasing exposure to heroin or to cocaine was associated greater odds of depression, with all cases and controls combined. In cases with an opioid dependence diagnosis, increasing cocaine exposure was associated with a further increase in odds of depression. However, in cases with a cocaine dependence diagnosis, increasing exposure to either cannabis or alcohol, as well as heroin, was associated with a further increase in odds of depression. Discussion and Conclusions This dimensional analysis of exposure to specific drugs provides insights on depression comorbidity with addictive diseases, and the impact of poly-drug exposure. Scientific Significance A rapid analysis of exposure to drugs of abuse reveals how specific patterns of drug and poly-drug exposure are associated with increasing odds of depression.

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Susceptibility loci for heroin and cocaine addiction in the serotonergic and adrenergic pathways in populations of different ancestry

Cited by 15 publications

References 74 publications

Non-medical Cannabis Self-Exposure as a Dimensional Predictor of Opioid Dependence Diagnosis: A Propensity Score Matched Analysis

Non-medical Cannabis Self-Exposure as a Dimensional Predictor of Opioid Dependence Diagnosis: A Propensity Score Matched Analysis

Influence of dopaminergic system gene polymorphisms on mixed amphetamine-type stimulants and opioid dependence in Malaysian Malays

Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

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