Risk of Heroin Dependence in Newly Incident Heroin Users

Rivera, Olga J. Santiago; Havens, Jennifer R.; Parker, Maria A.; Anthony, James C.

doi:10.1001/jamapsychiatry.2018.1214

Cited by 21 publications

(8 citation statements)

References 4 publications

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“…As discussed elsewhere (Cadet, 2019), because repeated drug use in humans is not enough to reach a SUD DSM-V diagnosis, we have added contingent footshocks during drug SA to encompass one additional DMS criterion, namely, compulsive drug taking in the presence of adverse consequences. This approach is consistent with the observations that, in clinical situations, only small percentages of individuals continue to misuse drugs when faced with legal and financial consequences (Anthony et al, 1994;Miller and Flaherty, 2000;Santiago Rivera et al, 2018). It needs to be also noted that there exists a substantial number of individuals who use opioids without meeting criteria for OUD (Korf et al, 2010;Zaaijer et al, 2014).…”

Section: Discussionsupporting

confidence: 86%

Escalated Oxycodone Self-Administration and Punishment: Differential Expression of Opioid Receptors and Immediate Early Genes in the Rat Dorsal Striatum and Prefrontal Cortex

Blackwood¹,

McCoy²,

Ladenheim³

et al. 2020

Front. Neurosci.

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Opioid use disorder (OUD) is characterized by compulsive drug taking despite adverse life consequences. Here, we sought to identify neurobiological consequences associated with the behavioral effects of contingent footshocks administered after escalation of oxycodone self-administration. To reach these goals, Sprague-Dawley rats were trained to self-administer oxycodone for 4 weeks and were then exposed to contingent electric footshocks. This paradigm helped to dichotomize rats into two distinct behavioral phenotypes: (1) those that reduce lever pressing (shock-sensitive) and (2) others that continue lever pressing (shock-resistant) for oxycodone during contingent punishment. The rats were euthanized at 2-h after the last oxycodone plus footshock session. The dorsal striata and prefrontal cortices were dissected for use in western blot and RT-qPCR analyses. All oxycodone self-administration rats showed significant decreased expression of Mu and Kappa opioid receptor proteins only in the dorsal striatum. However, expression of Delta opioid receptor protein was decreased in both brain regions. RT-qPCR analyses documented significant decreases in the expression of c-fos, fosB, fra2, junB, egr1, and egr2 mRNAs in the dorsal striatum (but not in PFC) of the shock-sensitive rats. In the PFC, junD expression was reduced in both phenotypes. However, egr3 mRNA expression was increased in the PFC of only shock-resistant rats. These results reveal that, similar to psychostimulants and alcohol, footshocks can dichotomize rats that escalated their intake of oxycodone into two distinct behavioral phenotypes. These animals also show significant differences in the mRNA expression of immediate early genes, mainly, in the dorsal striatum. The increases in PFC egr3 expression in the shock-resistant rats suggest that Egr3 might be involved in the persistence of oxycodone-associated memory under aversive conditions. This punishment-driven model may help to identify neurobiological substrates of persistent oxycodone taking and abstinence in the presence of adverse consequences.

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Section: Discussionsupporting

confidence: 86%

Escalated Oxycodone Self-Administration and Punishment: Differential Expression of Opioid Receptors and Immediate Early Genes in the Rat Dorsal Striatum and Prefrontal Cortex

Blackwood¹,

McCoy²,

Ladenheim³

et al. 2020

Front. Neurosci.

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“…The primary neurocircuitry elements involved (basal ganglia, extended amygdala, and prefrontal cortex) and their molecular connections to the cycle of addiction (intoxication, withdrawal, and preoccupation) are broadly understood. However, there is clear variability in the functioning of this neurocircuitry among individuals as evidenced by only 20–30% of people who use heroin becoming addicted 9 , 10 and only 8–12% of chronic pain patients prescribed opioids developing OA 11 .…”

Section: Introductionmentioning

confidence: 99%

Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond

Gaddis

Mathur

Marks

et al. 2022

Sci Rep

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Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10–9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.

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“…Opioid use continues to pose significant risk to individuals throughout the globe, especially in the United States. Data from population-based epidemiological surveys from 2002-2016 in the United States revealed that approximately 30% of individuals who started heroin use met DSM-IV criteria for opioid dependence within one year of initiation (1). In addition, the most recent estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study revealed that the global prevalence of opioid dependence was 510 people per population of 100,000, and the United States had the highest prevalence rate among all countries (1,347 persons per 100,000 population) (2).…”

Section: Introductionmentioning

confidence: 99%

Epigenome-Wide Study of Brain DNA Methylation Among Opioid Users and Controls

Shu

Sosnowski

Tao

et al. 2020

Preprint

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Opioid abuse poses significant risk to individuals in the United States and epigenetic changes are a leading potential biomarker of abuse. Current evidence, however, is mostly limited to candidate gene analysis in whole blood. To clarify the association between opioid abuse and DNA methylation, we conducted an epigenome-wide analysis (EWAS) of DNA methylation in brains of individuals who died from opioid intoxication and controls. Tissue samples were extracted from the dorsolateral prefrontal cortex of 160 deceased individuals (Mage = 35.15, SD = 9.42 years; 62% male; 78% White). The samples included 73 individuals who died of opioid intoxication, 59 group-matched psychiatric controls, and 28 group-matched normal controls. EWAS was implemented using the Illumina Infinium MethylationEPIC BeadChip; analyses adjusted for sociodemographic characteristics, negative control and ancestry principal components, cellular composition, and surrogate variables. Epigenetic age was calculated using the Horvath and Levine clocks, and gene ontology (GO) analyses were performed. No CpG sites were epigenome-wide significant after multiple testing correction, but 13 sites reached nominal significance (p < 1.0 x 10-5). There was a significant association between opioid use and Levine phenotypic age (b = 2.24, se = 1.11, p = .045). Opioid users were approximately two years phenotypically older compared to controls. GO analyses revealed enriched pathways related to cell function and neuron differentiation, but no terms survived multiple testing correction. Results inform our understanding of the neurobiology of opioid use, and future research with larger samples across stages of opioid use will elucidate the complex genomics of opioid abuse.

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Risk of Heroin Dependence in Newly Incident Heroin Users

Cited by 21 publications

References 4 publications

Escalated Oxycodone Self-Administration and Punishment: Differential Expression of Opioid Receptors and Immediate Early Genes in the Rat Dorsal Striatum and Prefrontal Cortex

Escalated Oxycodone Self-Administration and Punishment: Differential Expression of Opioid Receptors and Immediate Early Genes in the Rat Dorsal Striatum and Prefrontal Cortex

Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond

Epigenome-Wide Study of Brain DNA Methylation Among Opioid Users and Controls

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