Association between DRD2/ANKK1 TaqIA Allele Status and Striatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder

¹ Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Campus Mitte (CCM), 10117 Berlin, Germany

² Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, 30625 Hannover, Germany

³ Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany

⁴ Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), 20251 Hamburg, Germany

⁵ Berlin Institute of Health (BIH), 10178 Berlin, Germany

^*Correspondence: gianna.spitta@charite.de (Gianna Spitta)
Academic Editor: Pradeep Paudel

J. Integr. Neurosci. 2022, 21(6), 171; https://doi.org/10.31083/j.jin2106171

Submitted: 18 June 2022 | Revised: 30 August 2022 | Accepted: 31 August 2022 | Published: 28 October 2022

(This article belongs to the Special Issue Dopamine Receptors: Latest Advances and Prospects)

This is an open access article under the CC BY 4.0 license.

Abstract

Background: The association between blunted dopaminergic neurotransmission and alcohol use disorder (AUD) is well-known. In particular, the impairment of postsynaptic dopamine 2 and 3 receptors (DRD2/3) in the ventral and dorsal striatum during the development and maintenance of alcohol addiction has been investigated in several positron emission tomography (PET) studies. However, it is unclear whether these changes are the result of adaptation or genetic predisposition. Methods: Here we investigated the association between DRD2/ankyrin repeat and kinase domain-containing 1 (ANKK1) TaqIA allele (rs1800497) status and striatal DRD2/3 availability measured by 18F-fallypride PET in 12 AUD patients and 17 sex-matched healthy controls. Age and smoking status were included as covariates. Results: Contrary to our expectations, TaqIA allele status was not associated with striatal DRD2/3 availability in either group and there was no significant difference between groups, possibly due to the relatively small sample size (N = 29). Conclusions: Nonetheless, this is the first in vivo study investigating the relationship between dopamine receptor availability and genetic factors in AUD. The pitfalls of assessing such relationships in a relatively small sample are discussed. Clinical Trial Registration: The published analysis is an additional, post hoc analysis to the preregistered trial with clinical trial number NCT01679145 available on https://clinical-trials.gov/ct2/show/NCT01679145.

Keywords

alcohol use disorder

dopamine D2 and D3 receptor availability

DRD2/ANKK1 TaqIA allele status

18F-fallypride PET

Funding

FOR 1617: grants FR 3572/1-1, WA 1539/7-1, HE 2597/14-1, HE 2597/15-1, HE 2597/14 -2, HE 2597/15-2, GA 707/6-1, RA 1047/2-1, and RA 1047/2-2/Deutsche Forschungsgemeinschaft (DFG)

Figures

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Fig. 1.

DRD2/3 Receptor Availability per site/ phenotype/ allele status. Dopamine receptor D2 and 3 availability in the associative, sensorimotor and limbic striatum and allele status in individuals with AUD and HC. The D2/3 availability was measured in BP ${}_{\text{ND}}$ of 18F-fallypride for each of the three different ROIs and shown for patients (AUD) and controls (HC). A–, no risk allele; A+, at least 1 risk allele.

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J. Integr. Neurosci. Print ISSN 0219-6352 Electronic ISSN 1757-448X