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Novelty seeking mediates the effect of DRD3 variation on onset age of amphetamine dependence in Han Chinese population

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Abstract

The dopamine receptor D3 (DRD3) gene, one of the candidate genes for amphetamine dependence (AD), is involved in the mesolimbic dopaminergic system, implicated as the underlying mechanism of addiction. Our case–control study aimed to investigate whether the DRD3 gene is associated with the susceptibility to AD and specific personality traits in AD patients. A total of 1060 unrelated Han Chinese subjects (559 AD patients and 501 controls) were screened using the same assessment tool and genotyped for eight DRD3 polymorphisms. All patients met the DSM-IV-TR criteria for AD, and personality traits of 539 were assessed using a Tridimensional Personality Questionnaire. Furthermore, AD individuals were divided into four clinical subgroups based on gender and psychosis status, to reduce the clinical heterogeneity. We found that the ATA haplotype combination for SNPs rs324029, rs6280, and rs9825563, respectively, was significantly associated with total AD patients (p = 0.0003 after 10,000 permutations). Similar results were observed in the both male and non-psychosis subgroup but not in other subgroups. In addition, DRD3 rs9825563 may influence onset age of drug use, partially mediated by novelty seeking in the non-psychosis AD group. In conclusion, DRD3 is a potential genetic factor in the susceptibility to AD and is associated with onset age of drug use through interaction with novelty seeking in a specific patient group in the Han Chinese population.

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Abbreviations

AD:

Amphetamine dependence

DAT:

Dopamine transporter

DRD3:

Dopamine receptor D3

DRD4:

Dopamine receptor D4

DSM-IV-TR:

Diagnostic and statistical manual for mental disorders, 4th edition, text revision

HA:

Harm avoidance

LD:

Linkage disequilibrium

MA:

Methamphetamine

NS:

Novelty seeking

RD:

Reward dependence

SADS-L:

Schedule of affective disorder and schizophrenia-lifetime

SNP:

Single-nucleotide polymorphism

TPQ:

Tridimensional personality questionnaire

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Acknowledgments

This study was supported by grants from National Science Council MOST-103-2325-B-016-001(SYH), MOST-104-2314-B-016-012MY3(SYH), NSC101-2325-B-016-003(SYH); and by Grants from Tri-Service General Hospital TSGH-C103-133 (SYH), TSGH-C104-129 (SYH), TSGH-C105-124 (SYH), and TSGH-C104-126 (SCK), TSGH-C105-125 (SCK); and by Grants from Medical Affairs Bureau, Ministry of National Defense, Taiwan, MAB-104-073 (SYH). These funding agencies played no role in the study design, collection, analysis or interpretation of data, the writing of the report, or the decision to submit the paper for publication. We thank Miss Pi-Fen Tsui, Miss Mei-Chen Shih, and Miss Yun-Hsin Lin for their assistance in the preparation of this manuscript.

Author contributions

All authors contributed extensively to the work presented in this paper. SYH was the principal investigator for the study, conceived of the study, and helped to draft the manuscript. The authors SCK and SYH designed the study and wrote the protocol; SCK and YWY wrote the main manuscript text and data collection. SCK undertook the statistical analysis and wrote the first draft of the manuscript. The authors CYC, CCH, TYC, PSH, CSL, and CHY managed the literature searches and analyses. RBL supervised data collection and provided overall scientific supervision. All authors contributed to and have approved the final manuscript.

Author information

Authors and Affiliations

  1. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC

    Shin-Chang Kuo, Yi-Wei Yeh, Chun-Yen Chen, Chang-Chih Huang, Che-Hung Yen, Chih-Sung Liang & San-Yuan Huang

  2. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Road, Sec. 2, Nei-Hu District, Taipei, 144, Taiwan, ROC

    Shin-Chang Kuo, Yi-Wei Yeh, Chun-Yen Chen, Tien-Yu Chen & San-Yuan Huang

  3. Department of Psychiatry, Taipei Branch, Buddhist Tzu Chi General Hospital, Taipei, Taiwan

    Chang-Chih Huang

  4. Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC

    Che-Hung Yen

  5. Division of Neurology, Department of Internal Medicine, Chiayi Yang-Ming Hospital, Chiayi, Taiwan, ROC

    Che-Hung Yen

  6. Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC

    Chih-Sung Liang & Pei-Shen Ho

  7. Institute of Behavior Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

    Ru-Band Lu

Authors
  1. Shin-Chang Kuo
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  2. Yi-Wei Yeh
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  3. Chun-Yen Chen
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  4. Chang-Chih Huang
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  5. Tien-Yu Chen
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  6. Che-Hung Yen
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  7. Chih-Sung Liang
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  8. Pei-Shen Ho
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  9. Ru-Band Lu
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  10. San-Yuan Huang
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Corresponding author

Correspondence to San-Yuan Huang.

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Kuo, SC., Yeh, YW., Chen, CY. et al. Novelty seeking mediates the effect of DRD3 variation on onset age of amphetamine dependence in Han Chinese population. Eur Arch Psychiatry Clin Neurosci 268, 249–260 (2018). https://doi.org/10.1007/s00406-016-0754-x

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