scholarly journals Convergence of case-specific epigenetic alterations identify a confluence of genetic vulnerabilities tied to opioid dependence

2021 ◽  
Author(s):  
Olivia Corradin ◽  
Richard Sallari ◽  
An T. Hoang ◽  
Bibi S Kassim ◽  
Gabriella Ben Hutta ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Opioid Dependence ◽  
Opioid Use Disorder ◽  
Opioid Overdose ◽  
Opioid Use ◽  
Prefrontal Cortical ◽  
Patient Heterogeneity ◽  
Dorsolateral Prefrontal ◽  
Number Of Sexual Partners ◽  
Genetic And Environmental Factors

Opioid dependence is a highly heterogeneous disease driven by a variety of genetic and environmental risk factors which have yet to be fully elucidated. We interrogated the effects of opioid dependence on the brain using ChIP-seq to quantify patterns of H3K27 acetylation in dorsolateral prefrontal cortical neurons isolated from 51 opioid-overdose cases and 51 accidental death controls. Among opioid cases, we observed global hypoacetylation and identified 388 putative enhancers consistently depleted for H3K27ac. Machine learning on H3K27ac patterns predicts case-control status with high accuracy. We focus on case-specific regulatory alterations, revealing 81,399 hypoacetylation events, uncovering vast inter-patient heterogeneity. We developed a strategy to decode this heterogeneity based on convergence analysis, which leveraged promoter-capture Hi-C to identify five genes over-burdened by alterations in their regulatory network or "plexus": ASTN2, KCNMA1, DUSP4, GABBR2, ENOX1. These convergent loci are enriched for opioid use disorder risk genes and heritability for generalized anxiety, number of sexual partners, and years of education. Overall, our multi-pronged approach uncovers neurobiological aspects of opioid dependence and captures genetic and environmental factors perpetuating the opioid epidemic.

Opioid Use Disorder during Antepartum and Postpartum Hospitalizations

2019 ◽  
Vol 37 (14) ◽  
pp. 1467-1475
Author(s):  
Adina R. Kern-Goldberger ◽  
Yongmei Huang ◽  
Melanie Polin ◽  
Zainab Siddiq ◽  
Jason D. Wright ◽  
...  
Keyword(s):  
Opioid Dependence ◽  
Nationwide Inpatient Sample ◽  
Temporal Trends ◽  
Opioid Use Disorder ◽  
Opioid Overdose ◽  
Opioid Use ◽  
Chi Square ◽  
Cross Sectional ◽  
Chi Square Test ◽  
Sectional Analysis

Objective This study aimed to evaluate temporal trends in opioid use disorder (OUD) during antepartum and postpartum hospitalizations. Study Design This repeated cross-sectional analysis analyzed data from the National (Nationwide) Inpatient Sample. Women aged 15 to 54 years admitted antepartum or postpartum were identified. The presence of OUD was determined based on a diagnosis of opioid abuse, opioid dependence, or opioid overdose. Temporal trends in OUD were evaluated using the Rao–Scott chi-square test. Temporal trends in opioid overdose were additionally evaluated. Results An estimated 7,336,562 antepartum hospitalizations and 1,063,845 postpartum readmissions were included in this analysis. The presence of an OUD diagnosis during antepartum hospitalizations increased from 0.7% of patients in 1998 to 1999 to 2.9% in 2014 (p < 0.01) and during postpartum hospitalizations increased from 0.8% of patients in 1998 to 1999 to 2.1% of patients in 2014 (p < 0.01). Risk of overdose diagnoses increased significantly for both antepartum hospitalizations, from 22.7 per 100,000 hospitalizations in 1998 to 2000 to 70.3 per 100,000 hospitalizations in 2013 to 2014 (p < 0.001), and postpartum hospitalizations, from 18.8 per 100,000 hospitalizations in 1998 to 2000 to 65.2 per 100,000 hospitalizations in 2013 to 2014 (p = 0.02). Discussion Risk of OUD diagnoses and overdoses increased over the study period for both antepartum and postpartum hospitalizations.

scholarly journals Transcriptional alterations in opioid use disorder reveal an interplay between neuroinflammation and synaptic remodeling

2020 ◽  
Author(s):  
Marianne L. Seney ◽  
Sam Moon-Kim ◽  
Jill R. Glausier ◽  
Mariah A. Hildebrand ◽  
Xiangning Xue ◽  
...  
Keyword(s):  
Opioid Dependence ◽  
Dorsolateral Prefrontal Cortex ◽  
Opioid Use Disorder ◽  
Opioid Use ◽  
Synaptic Remodeling ◽  
Dorsolateral Prefrontal ◽  
Transcriptional Alterations ◽  
Postmortem Brains ◽  
High Degree ◽  
Overdose Deaths

AbstractPrevalence rates of opioid use disorder (OUD) have increased dramatically, accompanied by a surge of overdose deaths. While opioid dependence has been extensively studied in preclinical models, we still have a very limited understanding of the biological changes that occur in the brains of people who chronically use opioids and who are diagnosed with OUD. To address this, we conducted the largest transcriptomics study to date using postmortem brains from subjects with OUD. We focused on the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc), two regions heavily implicated in OUD. We discovered a high degree of overlap in transcripts between DLPFC and NAc in OUD, primarily associated with neuroinflammation. Moreover, additional transcripts were enriched for factors that control pro-inflammatory cytokine-mediated signaling and remodeling of the extracellular matrix (ECM). Our results also implicate a role for microglia as a critical driver for opioid-induced neuroplasticity. Overall, our findings reveal new connections between the brain’s immune system and opioid dependence in the human brain.

scholarly journals Assessing the Relationships Between COVID-19 Stay-at-Home Orders and Opioid Overdoses in the State of Pennsylvania

2021 ◽  
pp. 002204262110063
Author(s):  
Brian King ◽  
Ruchi Patel ◽  
Andrea Rishworth
Keyword(s):  
Age Groups ◽  
The United States ◽  
Opioid Use Disorder ◽  
Opioid Overdose ◽  
Policy Recommendations ◽  
Opioid Use ◽  
Fentanyl Analogs ◽  
Measure Change ◽  
Using Data ◽  
At Home

COVID-19 is compounding opioid use disorder throughout the United States. While recent commentaries provide useful policy recommendations, few studies examine the intersection of COVID-19 policy responses and patterns of opioid overdose. We examine opioid overdoses prior to and following the Pennsylvania stay-at-home order implemented on April 1, 2020. Using data from the Pennsylvania Overdose Information Network, we measure change in monthly incidents of opioid-related overdose pre- versus post-April 1, and the significance of change by gender, age, race, drug class, and naloxone doses administered. Findings demonstrate statistically significant increases in overdose incidents among both men and women, White and Black groups, and several age groups, most notably the 30–39 and 40–49 ranges, following April 1. Significant increases were observed for overdoses involving heroin, fentanyl, fentanyl analogs or other synthetic opioids, pharmaceutical opioids, and carfentanil. The study emphasizes the need for opioid use to be addressed alongside efforts to mitigate and manage COVID-19 infection.

Predicting Opioid Overdose Readmission and Opioid Use Disorder with Machine Learning

2020 ◽  
Author(s):  
Sarah McDougall ◽  
Priyanka Annapureddy ◽  
Praveen Madiraju ◽  
Nicole Fumo ◽  
Stephen Hargarten
Keyword(s):  
Machine Learning ◽  
Opioid Use Disorder ◽  
Opioid Overdose ◽  
Opioid Use

Using Bilateral tDCS to Modulate EEG Amplitude and Coherence of Men With Opioid Use Disorder Under Methadone Therapy: A Sham-controlled Clinical Trial

2021 ◽  
pp. 155005942110221
Author(s):  
Hossein Mostafavi ◽  
Mohsen Dadashi ◽  
Alireza Faridi ◽  
Fatemeh Kazemzadeh ◽  
Zakaria Eskandari
Keyword(s):  
Clinical Trial ◽  
Quantitative Eeg ◽  
Opioid Use Disorder ◽  
Controlled Clinical Trial ◽  
Opioid Use ◽  
Double Blind ◽  
Theta Waves ◽  
Dorsolateral Prefrontal ◽  
Male Patients ◽  
The Right

Objective. This study aimed to investigate the effect of bilateral transcranial direct current stimulation (tDCS) on the electroencephalography (EEG) amplitude and coherence in male patients with opioid use disorder (OUD), who were under methadone therapy. It compares the effects of active versus sham tDCS. Methods. This is a double-blind sham-controlled clinical trial. Participants were 30 male patients with OUD; they were divided into 3 groups of left anode/right cathode tDCS, right anode/left cathode tDCS, and sham tDCS. Their brainwave activity was measured by quantitative EEG before study and then active groups underwent tDCS (2 mA, 20 min) applied over their right/left dorsolateral prefrontal cortex (DLPFC) for 10 consecutive days. After stimulation, they were re-assessed. The collected data were analyzed in SPSS, MATLAB, and NeuroGuide v.2 applications. Results. After active tDCS, a significant decrease in amplitude of slow brain waves (delta, theta, and alpha) in prefrontal, frontal, occipital, and parietal areas, and an increase in the coherence of beta, delta, and theta frequency bands in the parietal, central, and temporal regions of addicts were reported. In the sham group, there was a significant decrease in the amplitude of the alpha wave and in the coherence of delta and theta waves. Conclusion. The active tDCS over the right/left DLPFC, as a noninvasive and complementary treatment, can modulate the amplitude and coherence of brainwaves in patients with OUD.

scholarly journals Vitamin D deficiency exacerbates UV/endorphin and opioid addiction

2021 ◽  
Vol 7 (24) ◽  
pp. eabe4577
Author(s):  
Lajos V. Kemény ◽  
Kathleen C. Robinson ◽  
Andrea L. Hermann ◽  
Deena M. Walker ◽  
Susan Regan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Opioid Use Disorder ◽  
Opioid Addiction ◽  
Opioid Use ◽  
Endogenous Opioid ◽  
Evolutionary Advantage ◽  
Seeking Behavior ◽  
Genetic And Environmental Factors ◽  
Dose Dependent ◽  
Genetic Mouse Models

The current opioid epidemic warrants a better understanding of genetic and environmental factors that contribute to opioid addiction. Here we report an increased prevalence of vitamin D (VitD) deficiency in patients diagnosed with opioid use disorder and an inverse and dose-dependent association of VitD levels with self-reported opioid use. We used multiple pharmacologic approaches and genetic mouse models and found that deficiencies in VitD signaling amplify exogenous opioid responses that are normalized upon restoration of VitD signaling. Similarly, physiologic endogenous opioid analgesia and reward responses triggered by ultraviolet (UV) radiation are repressed by VitD signaling, suggesting that a feedback loop exists whereby VitD deficiency produces increased UV/endorphin-seeking behavior until VitD levels are restored by cutaneous VitD synthesis. This feedback may carry the evolutionary advantage of maximizing VitD synthesis. However, unlike UV exposure, exogenous opioid use is not followed by VitD synthesis (and its opioid suppressive effects), contributing to maladaptive addictive behavior.

scholarly journals Health care utilization and overall costs based on opioid dependence in patients undergoing surgery for degenerative spondylolisthesis

2018 ◽  
Vol 44 (5) ◽  
pp. E14 ◽  
Author(s):  
Mayur Sharma ◽  
Beatrice Ugiliweneza ◽  
Zaid Aljuboori ◽  
Maxwell Boakye
Keyword(s):  
Health Care ◽  
Health Care Utilization ◽  
Opioid Dependence ◽  
Degenerative Spondylolisthesis ◽  
Opioid Use Disorder ◽  
Hospital Length Of Stay ◽  
Care Utilization ◽  
Opioid Use ◽  
Opioid Dependency ◽  
Linear Contrasts

OBJECTIVEOpioid abuse is highly prevalent in patients with back pain. The aim of this study was to identify health care utilization and overall costs associated with opioid dependence in patients undergoing surgery for degenerative spondylolisthesis (DS).METHODSThe authors queried the MarketScan database using ICD-9 and CPT-4 codes from 2000 to 2012. Opioid dependency was defined as having a diagnosis of opioid use disorder, having a prescription for opioid use disorder, or having 10 or more opioid prescriptions. Opioid dependency was evaluated in 12-month period leading to surgery and in the period 3–15 months following the procedure. Patients were segregated into 4 groups based on opioid dependence before and after surgery: group NDND (prior nondependent who remain nondependent), group NDD (prior nondependent who become dependent), group DND (prior dependent who become nondependent), and group DD (prior dependent who remain dependent). The outcomes of interest were discharge disposition, hospital length of stay (LOS), complications, and health care resource costs. The 4 groups were compared using the Kruskal-Wallis test and linear contrasts built from generalized regression models.RESULTSA total of 10,708 patients were identified, with 81.57%, 3.58%, 8.54%, and 6.32% of patients in groups NDND, NDD, DND, and DD, respectively. In group DD, 96.31% of patients had decompression with fusion, compared with 93.59% in group NDND. Patients in group NDD, DND, and DD had longer hospital LOS compared with those in group NDND. Patients in group DD were less likely to be discharged home compared with those in group NDND (odds ratio 0.639, 95% confidence interval 0.52–0.785). At 3–15 months postdischarge, patients in group DD incurred 21% higher hospital readmission costs compared with those in group NDND. However, patients in groups NDD and DD were likely to incur 2.8 times the overall costs compared with patients in group NDND (p < 0.001) at 3–15 months after surgery (median overall payments: group NDD $20,033 and group DD $19,654, vs group NDND $7994).CONCLUSIONSPatients who continued to be opioid dependent or became opioid dependent following surgery for DS incurred significantly higher health care utilization and costs within 3 months and in the period 3–15 months after discharge from surgery.

Use of Buprenorphine for the Treatment of Opioid Use Disorder

2020 ◽  
pp. 155-168
Author(s):  
Paul J. Fudala ◽  
Anne Cramer Andorn
Keyword(s):  
Opioid Dependence ◽  
Addiction Treatment ◽  
Partial Agonist ◽  
The United States ◽  
Opioid Use Disorder ◽  
Sublingual Administration ◽  
Opioid Use ◽  
The Us ◽  
Monthly Administration ◽  
Drug Addiction Treatment

Buprenorphine is a mu-opioid partial agonist that was first developed as a parenteral analgesic and subsequently as a treatment for opioid dependence. In the United States, the first two products approved by the US Food and Drug Administration (in 2002) for the latter indication were buprenorphine (Subutex) and buprenorphine/naloxone (Suboxone) tablet formulations for sublingual administration. Since that time, additional products for both sublingual and buccal administration have also been approved, as well as a subcutaneous injection for once-monthly administration for the treatment of moderate or severe opioid use disorder (OUD) and a subdermal implant for the maintenance treatment of opioid dependence that delivers buprenorphine over a 6-month period. Under the Drug Addiction Treatment Act of 2000 (DATA 2000), qualified practitioners may apply for waivers to treat opioid dependence/OUD with approved buprenorphine products in any setting in which they are qualified to practice. Like other opioids, buprenorphine has the potential for being misused and abused.

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