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. 2019 Oct 18:2019:236084.

Bi-directional Acceleration of Alcohol Use and Opioid Use Disorder

Wenfei Huang  1   2 , Erika P Penaherrera  1 , Danaika F Desir  1 , Dominick L Gamarro  1 , Jessica Cottrell  1 , Tinchun Chu  1 , Sulie L Chang  1   2
Affiliations

Bi-directional Acceleration of Alcohol Use and Opioid Use Disorder

Wenfei Huang et al. J Drug Alcohol Res. .

Abstract

Alcohol is the most widely used addictive substance. Severe alcohol abuse is diagnosed as "alcohol use disorder" (AUD). A common and harmful drinking pattern is binge drinking that elevates a person's blood alcohol concentration to ≥ 0.08%. Such drinking may be an early indicator of AUD. Opioid misuse and dependence have become worldwide crises. Patterned consumption of various opioids can develop into opioid use disorder (OUD). An intertwined epidemic exists between opioid abuse, alcohol addiction, and binge drinking. Currently, studies on the interaction of AUD and OUD are limited and the underlying mechanisms linking these disorders remains unclear. We reviewed studies on AUD and OUD and utilized Ingenuity Pathway Analysis (IPA) to identify mechanisms of AUD and OUD interaction and potential gene targets for therapeutic agents. According to IPA Canonical Pathways Analysis, Gamma-aminobutyric Acid (GABA) Receptor Signaling, Neuroinflammation Signaling Pathway, Opioid Signaling Pathway and Dopamine-DARPP32 Feedback in cAMP Signaling are potential contributors to the interaction of AUD and OUD.

Keywords: alcohol abuse; alcohol use disorder; ingenuity pathway analysis; opioid dependence; opioid use disorder.

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Conflict of interest statement

8. Conflict of interest The authors declare that there is no conflict of interest.

Figures

Figure 1:
Figure 1:
Genes that might contribute to interaction of alcohol abuse/AUD and OUD, as identified using IPA.
Figure 2:
Figure 2:
Canonical pathway analysis of the genes related to AUD and OUD, as analyzed using IPA core analysis. The gene set was imported into IPA for canonical pathway analysis. Such pathways were scored by analyzing the ratio of the number of genes that map to the pathway. The pathways are presented according to the negative base10 logarithm of the p value obtained using the Fisher exact test.
Figure 3:
Figure 3:
Overlapping of the canonical pathways predicted to contribute to interaction of AUD and OUD. Interactions between predicted pathways were analysed based on overlap of the genes in the canonical pathways. Seven top pathways are highlighted: Gamma-aminobutyric Acid (GABA) Receptor Signaling, Neuroinflammation Signaling, Opioid Signaling, dopamine-DARPP32 feedback in cAMP signaling, Circadian Rhythm Signalling, nNOS Signaling in Neurons and Glutamate Receptor Signalling. The P values of the 7 pathways are labelled beside the pathway.
Figure 4:
Figure 4:
Predicted contribution of signalling pathways to interaction of AUD and OUD. Orange arrow refers to the interaction of AUD and OUD. Blue arrow refers to predicted involvement of the pathways in the interaction of AUD and OUD. Green dash arrows and green notes refer to correlations between pathways and disorder symptoms supported by literatures.
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