Focusing on the Opioid System for Addiction Biomarker Discovery

Trends in Molecular Medicine

Volumn 24, Issue 2, 2018, Pages 206-220

  Belzeaux, Raoul ^a,b,f   Lalanne, Laurence ^c,d   Kieffer, Brigitte L ^a   Lutz, Pierre Eric ^a,e  

^a MCGILL UNIVERSITY   (Canada)

^b ASSISTANCE PUBLIQUE HÔPITAUX DE MARSEILLE   (France)

^c UNIVERSITÉ DE STRASBOURG   (France)

^d UNIVERSITY HOSPITAL OF STRASBOURG   (France)

^e CNRS   (France)

^f AIX MARSEILLE UNIVERSITY   (France)

Author keywords

addiction; biomarker; brain imaging; epigenetic; genetic; opioid receptor

Indexed keywords

DELTA OPIATE RECEPTOR; KAPPA OPIATE RECEPTOR; MU OPIATE RECEPTOR; BIOLOGICAL MARKER; OPIATE RECEPTOR;

ALCOHOL CONSUMPTION; BEHAVIORAL ADDICTION; BINGE EATING DISORDER; CPG ISLAND; DECISION MAKING; DNA METHYLATION; DRUG DEPENDENCE; ENZYME ACTIVATION; EPIGENETICS; EXOSOME; FEASIBILITY STUDY; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENOME-WIDE ASSOCIATION STUDY; HUMAN; INDUCED PLURIPOTENT STEM CELL; NEONATAL ABSTINENCE SYNDROME; NONHUMAN; PATHOPHYSIOLOGY; PHARMACOGENOMICS; POSITRON EMISSION TOMOGRAPHY; PROTEIN BINDING; REVIEW; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SKIN BIOPSY; TRANSCRIPTOMICS; ADDICTION; METABOLISM;

BEHAVIOR, ADDICTIVE; BIOMARKERS; HUMANS; RECEPTORS, OPIOID; SUBSTANCE-RELATED DISORDERS;

EID: 85041091319     PISSN: 14714914     EISSN: 1471499X     Source Type: Journal    
DOI: 10.1016/j.molmed.2017.12.004     Document Type: Review

References (117)

1. Grant, B.F., et al. Epidemiology of DSM-5 drug use disorder: results from the national epidemiologic survey on alcohol and related conditions-III. JAMA Psychiatry 73 (2016), 39–47.
2. Yau, Y.H., Potenza, M.N., Gambling disorder and other behavioral addictions: recognition and treatment. Harv. Rev. Psychiatry 23 (2015), 134–146.
3. Ambermoon, P., et al. Compulsive use of dopamine replacement therapy: a model for stimulant drug addiction?. Addiction 107 (2012), 241–247.
4. Davies, M.N., et al. Functional annotation of the human brain methylome identifies tissue–specific epigenetic variation across brain and blood. Genome Biol., 13, 2012, R43.
5. Tylee, D.S., et al. On the outside, looking in: a review and evaluation of the comparability of blood and brain “-omes”. Am. J. Med. Genet. B Neuropsychiatr. Genet. 162B (2013), 595–603.
6. Lohoff, F.W., et al. Methylomic profiling and replication implicates deregulation of PCSK9 in alcohol use disorder. Mol. Psychiatry, 2017, 10.1038/mp.2017.168 Published online August 29, 2017.
7. Zappulli, V., et al. Extracellular vesicles and intercellular communication within the nervous system. J. Clin. Invest. 126 (2016), 1198–1207.
8. Shao, H., et al. Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma. Nat. Commun., 6, 2015, 6999.
9. Fell, G.L., et al. Skin beta-endorphin mediates addiction to UV light. Cell 157 (2014), 1527–1534.
10. Buhler, K.M., et al. Common single nucleotide variants underlying drug addiction: more than a decade of research. Addict. Biol. 20 (2015), 845–871.
11. Xuei, X., et al. Association of the kappa-opioid system with alcohol dependence. Mol. Psychiatry 11 (2006), 1016–1024.
12. Agrawal, A., et al. Meta-analyses of genome-wide association data hold new promise for addiction genetics. J. Stud. Alcohol Drugs 77 (2016), 676–680.
13. Ducci, F., Goldman, D., The genetic basis of addictive disorders. Psychiatr. Clin. North Am. 35 (2012), 495–519.
14. Verhagen, M., et al. A systematic review of the A118G (Asn40Asp) variant of OPRM1 in relation to smoking initiation, nicotine dependence and smoking cessation. Pharmacogenomics 13 (2012), 917–933.
15. Kong, X., et al. Lack of associations of the opioid receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) with alcohol dependence: review and meta-analysis of retrospective controlled studies. BMC Med. Genet., 18, 2017, 120.
16. Libbrecht, M.W., Noble, W.S., Machine learning applications in genetics and genomics. Nat. Rev. Genet. 16 (2015), 321–332.
17. Hancock, D.B., et al. Cis-expression quantitative trait loci mapping reveals replicable associations with heroin addiction in OPRM1. Biol. Psychiatry 78 (2015), 474–484.
18. Zhang, D., et al. Effect of mu-opioid receptor gene polymorphisms on heroin-induced subjective responses in a Chinese population. Biol. Psychiatry 61 (2007), 1244–1251.
19. Dlugos, A.M., et al. OPRM1 gene variants modulate amphetamine-induced euphoria in humans. Genes Brain Behav. 10 (2011), 199–209.
20. Wachman, E.M., et al. Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome. J. Am. Med. Assoc. 309 (2013), 1821–1827.
21. Wachman, E.M., et al. Variations in opioid receptor genes in neonatal abstinence syndrome. Drug Alcohol Depend. 155 (2015), 253–259.
22. Smith, A.H., et al. Genome-wide association study of therapeutic opioid dosing identifies a novel locus upstream of OPRM1. Mol. Psychiatry 22 (2017), 346–352.
23. Garbutt, J.C., et al. Clinical and biological moderators of response to naltrexone in alcohol dependence: a systematic review of the evidence. Addiction 109 (2014), 1274–1284.
24. Oslin, D.W., et al. Naltrexone vs placebo for the treatment of alcohol dependence: a randomized clinical trial. JAMA Psychiatry 72 (2015), 430–437.
25. Bilbao, A., et al. A pharmacogenetic determinant of mu-opioid receptor antagonist effects on alcohol reward and consumption: evidence from humanized mice. Biol. Psychiatry 77 (2015), 850–858.
26. Ramchandani, V.A., et al. A genetic determinant of the striatal dopamine response to alcohol in men. Mol. Psychiatry 16 (2011), 809–817.
27. Bernardi, R.E., et al. A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology. Transl. Psychiatry, 6, 2016, e861.
28. Zhang, Y., et al. Mouse model of the OPRM1 (A118G) polymorphism: differential heroin self-administration behavior compared with wild-type mice. Neuropsychopharmacology 40 (2014), 1091–1100.
29. Henderson-Redmond, A.N., et al. Morphine-induced antinociception and reward in “humanized” mice expressing the mu opioid receptor A118G polymorphism. Brain Res. Bull. 123 (2016), 5–12.
30. Robinson, J.E., et al. Receptor reserve moderates mesolimbic responses to opioids in a humanized mouse model of the OPRM1 A118G polymorphism. Neuropsychopharmacology 40 (2015), 2614–2622.
31. Mague, S.D., et al. Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior. Proc. Natl. Acad. Sci. U. S. A. 106 (2009), 10847–10852.
32. Mague, S.D., Blendy, J.A., OPRM1 SNP (A118G): involvement in disease development, treatment response, and animal models. Drug Alcohol Depend. 108 (2010), 172–182.
33. Berrettini, W., Complexities of the mu opioid receptor. Biol. Psychiatry 77 (2015), 844–845.
34. Pena, C.J., et al. Epigenetic signaling in psychiatric disorders. J. Mol. Biol. 16 (2014), 281–295.
35. Clark, S.L., et al. Combined whole methylome and genomewide association study implicates CNTN4 in alcohol use. Alcohol. Clin. Exp. Res. 39 (2015), 1396–1405.
36. Liu, C., et al. A DNA methylation biomarker of alcohol consumption. Mol. Psychiatry, 2016, 10.1038/mp.2016.192 Published online November 15, 2016.
37. Zhang, H., et al. Array-based profiling of DNA methylation changes associated with alcohol dependence. Alcohol. Clin. Exp. Res. 37:Suppl 1 (2013), E108–E1015.
38. Marie-Claire, C., et al. Variability of response to methadone: genome-wide DNA methylation analysis in two independent cohorts. Epigenomics 8 (2016), 181–195.
39. Feng, J., et al. Role of Tet1 and 5-hydroxymethylcytosine in cocaine action. Nat. Neurosci. 18 (2015), 536–544.
40. Vassoler, F.M., et al. Epigenetic inheritance of a cocaine-resistance phenotype. Nat. Neurosci. 16 (2013), 42–47.
41. Nielsen, D.A., et al. Increased OPRM1 DNA methylation in lymphocytes of methadone-maintained former heroin addicts. Neuropsychopharmacology 34 (2009), 867–873.
42. Doehring, A., et al. Chronic opioid use is associated with increased DNA methylation correlating with increased clinical pain. Pain 154 (2013), 15–23.
43. Ebrahimi, G., et al. Elevated levels of DNA methylation at the OPRM1 promoter region in men with opioid use disorder. Am. J. Drug Alcohol Abuse, 2017, 10.1080/00952990.2016.1275659 Published online January 25, 2017.
44. Wachman, E.M., et al. Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome. J. Pediatr. 165 (2014), 472–478.
45. Nielsen, D.A., et al. Ethnic diversity of DNA methylation in the OPRM1 promoter region in lymphocytes of heroin addicts. Hum. Genet. 127 (2010), 639–649.
46. Dempster, E.L., et al. Genome-wide methylomic analysis of monozygotic twins discordant for adolescent depression. Biol. Psychiatry 76 (2014), 977–983.
47. Castillo-Fernandez, J.E., et al. Epigenetics of discordant monozygotic twins: implications for disease. Genome Med., 6, 2014, 60.
48. Oertel, B.G., et al. Genetic-epigenetic interaction modulates mu-opioid receptor regulation. Hum. Mol. Genet. 21 (2012), 4751–4760.
49. Lutz, P.E., et al. Epigenetic regulation of the kappa opioid receptor by child abuse. Biol. Psychiatry, 2017, 10.1016/j.biopsych.2017.07.012 Published online July 27, 2017.
50. Pietrzak, R.H., et al. Association of in vivo kappa-opioid receptor availability and the transdiagnostic dimensional expression of trauma-related psychopathology. JAMA Psychiatry 71 (2014), 1262–1270.
51. Yuferov, V., et al. Tissue-specific DNA methylation of the human prodynorphin gene in post-mortem brain tissues and PBMCs. Pharmacogenet. Genomics 21 (2011), 185–196.
52. Jenkinson, G., et al. Potential energy landscapes identify the information-theoretic nature of the epigenome. Nat. Genet. 49 (2017), 719–729.
53. Ziller, M.J., et al. Coverage recommendations for methylation analysis by whole-genome bisulfite sequencing. Nat. Methods 12 (2015), 230–232.
54. Wahl, S., et al. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature 541 (2017), 81–86.
55. Liu, Y., et al. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse. Sci. Rep., 5, 2015, 17543.
56. He, Y., et al. Regulation of opioid tolerance by let-7 family microRNA targeting the {micro} opioid receptor. J. Neurosci. 30 (2010), 10251–10258.
57. Wei, L.N., Loh, H.H., Transcriptional and epigenetic regulation of opioid receptor genes: present and future. Annu. Rev. Pharmacol. Toxicol. 51 (2011), 75–97.
58. Xu, J., et al. Stabilization of morphine tolerance with long-term dosing: association with selective upregulation of mu-opioid receptor splice variant mRNAs. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), 279–284.
59. Xu, J., et al. Alternatively spliced mu opioid receptor C termini impact the diverse actions of morphine. J. Clin. Invest. 127 (2017), 1561–1573.
60. Darcq, E., et al. RSK2 signaling in medial habenula contributes to acute morphine analgesia. Neuropsychopharmacology 37 (2012), 1288–1296.
61. Steiner, D., et al. Regulation of adenylate cyclase type VIII splice variants by acute and chronic Gi/o-coupled receptor activation. Biochem. J. 386:Pt 2 (2005), 341–348.
62. Zachariou, V., et al. Distinct roles of adenylyl cyclases 1 and 8 in opiate dependence: behavioral, electrophysiological, and molecular studies. Biol. Psychiatry 63 (2008), 1013–1021.
63. Jolas, T., et al. Chronic morphine increases GABA tone on serotonergic neurons of the dorsal raphe nucleus: association with an up-regulation of the cyclic AMP pathway. Neuroscience 95 (2000), 433–443.
64. Sillivan, S.E., et al. ELK1 transcription factor linked to dysregulated striatal Mu opioid receptor signaling network and OPRM1 polymorphism in human heroin abusers. Biol. Psychiatry 74 (2013), 511–519.
65. Toskulkao, T., et al. Alteration of lymphocyte opioid receptors in methadone maintenance subjects. Neurochem. Int. 56 (2010), 285–290.
66. Breen, M.S., et al. Systematic review of blood transcriptome profiling in neuropsychiatric disorders: guidelines for biomarker discovery. Hum. Psychopharmacol. 31 (2016), 373–381.
67. Li, M.D., et al. Transcriptome profiling and pathway analysis of genes expressed differentially in participants with or without a positive response to topiramate treatment for methamphetamine addiction. BMC Med. Genomics, 7, 2014, 65.
68. Zubieta, J.K., et al. Increased mu opioid receptor binding detected by PET in cocaine-dependent men is associated with cocaine craving. Nat. Med. 2 (1996), 1225–1229.
69. Ghitza, U.E., et al. Brain mu-opioid receptor binding predicts treatment outcome in cocaine-abusing outpatients. Biol. Psychiatry 68 (2010), 697–703.
70. Heinz, A., et al. Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil. Arch. Gen. Psychiatry 62 (2005), 57–64.
71. Weerts, E.M., et al. Positron emission tomography imaging of mu- and delta-opioid receptor binding in alcohol-dependent and healthy control subjects. Alcohol. Clin. Exp. Res. 35 (2011), 2162–2173.
72. Bencherif, B., et al. Regional mu-opioid receptor binding in insular cortex is decreased in bulimia nervosa and correlates inversely with fasting behavior. J. Nucl. Med. 46 (2005), 1349–1351.
73. Hermann, D., et al. Low mu-opioid receptor status in alcohol dependence identified by combined positron emission tomography and post-mortem brain analysis. Neuropsychopharmacology 42 (2017), 606–614.
74. Greenwald, M.K., et al. Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy. Drug Alcohol Depend. 144 (2014), 1–11.
75. Scott, D.J., et al. Smoking modulation of mu-opioid and dopamine D2 receptor-mediated neurotransmission in humans. Neuropsychopharmacology 32 (2007), 450–457.
76. Lutz, P.E., Kieffer, B.L., The multiple facets of opioid receptor function: implications for addiction. Curr. Opin. Neurobiol. 23 (2013), 473–479.
77. Ray, R., et al. Association of OPRM1 A118G variant with the relative reinforcing value of nicotine. Psychopharmacology (Berl) 188 (2006), 355–363.
78. Weerts, E.M., et al. Differences in delta- and mu-opioid receptor blockade measured by positron emission tomography in naltrexone-treated recently abstinent alcohol-dependent subjects. Neuropsychopharmacology 33 (2008), 653–665.
79. Mick, I., et al. Blunted endogenous opioid release following an oral amphetamine challenge in pathological gamblers. Neuropsychopharmacology 41 (2016), 1742–1750.
80. Majuri, J., et al. Dopamine and opioid neurotransmission in behavioral addictions: a comparative PET study in pathological gambling and binge eating. Neuropsychopharmacology 42 (2017), 1169–1177.
81. Richiardi, J., et al. BRAIN NETWORKS. Correlated gene expression supports synchronous activity in brain networks. Science 348 (2015), 1241–1244.
82. Heitzeg, M.M., et al. Neuroimaging risk markers for substance abuse: recent findings on inhibitory control and reward system functioning. Curr. Addict. Rep. 2 (2015), 91–103.
83. orris, L.S., et al. Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals. Addict. Biol., 2017, 10.1111/adb.12503 Published February 27, 2017.
84. Mechling, A.E., et al. Deletion of the mu opioid receptor gene in mice reshapes the reward-aversion connectome. Proc. Natl. Acad. Sci. U. S. A. 113 (2016), 11603–11608.
85. Cosa, A., et al. Multi-modal MRI classifiers identify excessive alcohol consumption and treatment effects in the brain. Addict. Biol. 22 (2017), 1459–1472.
86. Verbelen, M., et al. Cost-effectiveness of pharmacogenetic-guided treatment: are we there yet?. Pharmacogenomics J. 17 (2017), 395–402.
87. Marques, S., et al. Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system. Science 352 (2016), 1326–1329.
88. Zeisel, A., et al. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347 (2015), 1138–1142.
89. Mo, A., et al. Epigenomic signatures of neuronal diversity in the mammalian brain. Neuron 86 (2015), 1369–1384.
90. Warner-Schmidt, J.L., et al. Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 11360–11365.
91. Schmidt, E.F., et al. Identification of the cortical neurons that mediate antidepressant responses. Cell 149 (2012), 1152–1163.
92. Jalabert, M., et al. Neuronal circuits underlying acute morphine action on dopamine neurons. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 16446–16450.
93. Shippenberg, T.S., Herz, A., Differential effects of mu and kappa opioid systems on motivational processes. NIDA Res. Monogr. 75 (1986), 563–566.
94. Lalanne, L., et al. The kappa opioid receptor: from addiction to depression, and back. Front. Psychiatry, 5, 2014, 170.
95. Goeldner, C., et al. Impaired emotional-like behavior and serotonergic function during protracted abstinence from chronic morphine. Biol. Psychiatry 69 (2011), 236–244.
96. Lutz, P.E., et al. Distinct mu, delta, and kappa opioid receptor mechanisms underlie low sociability and depressive-like behaviors during heroin abstinence. Neuropsychopharmacology 39 (2014), 2694–2705.
97. Charbogne, P., et al. Mu opioid receptors in gamma-aminobutyric acidergic forebrain neurons moderate motivation for heroin and palatable food. Biol. Psychiatry 81 (2017), 778–788.
98. Corder, G., et al. Constitutive mu-opioid receptor activity leads to long-term endogenous analgesia and dependence. Science 341 (2013), 1394–1399.
99. Al-Hasani, R., Bruchas, M.R., Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology 115 (2011), 1363–1381.
100. Irannejad, R., et al. Functional selectivity of GPCR-directed drug action through location bias. Nat. Chem. Biol. 13 (2017), 799–806.
101. Epstein, D.H., et al. Promoting abstinence from cocaine and heroin with a methadone dose increase and a novel contingency. Drug Alcohol Depend. 101 (2009), 92–100.
102. Aboujaoude, E., Salame, W.O., Naltrexone: a pan-addiction treatment?. CNS Drugs 30 (2016), 719–733.
103. Bravo, M.J., et al. Methadone maintenance treatment: a protective factor for cocaine injection in a street-recruited cohort of heroin users. Drug Alcohol Depend. 112 (2010), 62–68.
104. Manglik, A., et al. Structure-based discovery of opioid analgesics with reduced side effects. Nature 537 (2016), 185–190.
105. Berger, A.C., Whistler, J.L., Morphine-induced mu opioid receptor trafficking enhances reward yet prevents compulsive drug use. EMBO Mol. Med. 3 (2011), 385–397.
106. Schmid, C.L., et al. Bias factor and therapeutic window correlate to predict safer opioid analgesics. Cell, 171, 2017 1165–1175. e13.
107. Bigliardi, P.L., et al. Opioids and skin homeostasis, regeneration and ageing – what's the evidence?. Exp. Dermatol. 25 (2016), 586–591.
108. Bodnar, R.J., Endogenous opiates and behavior: 2015. Peptides 88 (2017), 126–188.
109. Di Meo, A., et al. Liquid biopsy: a step forward towards precision medicine in urologic malignancies. Mol. Cancer, 16, 2017, 80.
110. Sheng, Y., et al. Using iPSC-derived human DA neurons from opioid-dependent subjects to study dopamine dynamics. Brain Behav., 6, 2016, e00491.
111. Lieberman, R., et al. Examining the effects of alcohol on GABAA receptor mRNA expression and function in neural cultures generated from control and alcohol dependent donor induced pluripotent stem cells. Alcohol 66 (2017), 45–53.
112. Ninkovic, J., Roy, S., Role of the mu-opioid receptor in opioid modulation of immune function. Amino Acids 45 (2013), 9–24.
113. Smith, A.K., et al. DNA extracted from saliva for methylation studies of psychiatric traits: evidence tissue specificity and relatedness to brain. Am. J. Med. Genet. B Neuropsychiatr. Genet. 168B (2015), 36–44.
114. Chu Sin Chung, P., Kieffer, B.L., Delta opioid receptors in brain function and diseases. Pharmacol. Ther. 140 (2013), 112–120.
115. Olmstead, M.C., et al. Mu and delta opioid receptors oppositely regulate motor impulsivity in the signaled nose poke task. PLoS One, 4, 2009, e4410.
116. Lutz, P.E., Kieffer, B.L., Opioid receptors: distinct roles in mood disorders. Trends Neurosci. 36 (2013), 195–206.
117. Edgar, R.D., et al. BECon: a tool for interpreting DNA methylation findings from blood in the context of brain. Transl. Psychiatry, 7, 2017, e1187.