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Influence of dopamine-related genes on craving, impulsivity, and aggressiveness in Korean males with alcohol use disorder

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Abstract

Dopamine is a major neuromodulator that is acutely involved in various cognitive processes, reward-motivated behaviors, and impulsivity. Abnormality in dopaminergic neurotransmission is implicated in the pathophysiology of alcohol use disorder (AUD). The present study examined the genetic influence of dopamine system on problematic drinking, impulsivity, and aggressiveness in a Korean male population with AUD. Five single nucleotide polymorphisms (SNPs) (rs4532 in DRD1, rs2283265 in DRD2, rs6280 in DRD3, rs1800497 in ANKK1, and rs4680 in COMT) and a variable number of tandem repeats (VNTRs) in DAT1 in 295 male patients with AUD were genotyped. For AUD-related clinical characteristics, the Alcohol Use Disorders Identification Test and the Obsessive–Compulsive Drinking Scale (OCDS) were used to assess the severity of hazardous drinking and craving symptoms, respectively. Participants also completed the UPPS-P Impulsive Behavior Scale (UPPS-P) and Buss-Perry Aggression Questionnaire (BPAQ). Analyses were performed using R package SNPassoc; statistical significance was set as p < 0.0083 after Bonferroni correction. A significant association was detected between DRD3 SNP rs6280 and OCDS scores. In regard to impulsivity and aggressiveness, rs4532 of DRD1 was significantly associated with UPPS-P score. Also, rs4532 demonstrated a nominally significant association with BPAQ score, although it did not reach statistical significance after correction for multiple comparisons. Results of this study support the idea that genetic variations in the dopamine system may contribute to alcohol cravings and impulsivity in patients with AUD.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2018R1A2B2007714). The funding source did not give any influences on the study design, data collection, analysis and interpretation of data, the writing of the report, and the decision to submit the paper for publication.

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SK and JK conceived and planned the study. SK contributed to data collection and management. CP, HK, and JK performed statistical analyses and interpreted the findings. CP, JK, SH and SK wrote the manuscript. SH and HK provided scientific input and helped edit the manuscript. All authors contributed to and have approved the final manuscript.

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Correspondence to Jee In Kang or Se Joo Kim.

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Park, C.I., Kim, H.W., Hwang, S.S. et al. Influence of dopamine-related genes on craving, impulsivity, and aggressiveness in Korean males with alcohol use disorder. Eur Arch Psychiatry Clin Neurosci 271, 865–872 (2021). https://doi.org/10.1007/s00406-019-01072-3

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