Alpha-synuclein and heroin craving in opiate-dependent patients on injectable heroin maintenance

Authors

  • Kenneth M. Dürsteler-MacFarland,

    Corresponding author
    1. Division of Substance Use Disorders, Psychiatric Hospital of the University of Basel, Switzerland
    2. Division of Substance Use Disorders, Psychiatric University Hospital of Zurich, Switzerland
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    • Both authors contributed equally.

  • Isabelle Brugger,

    1. Division of Substance Use Disorders, Psychiatric Hospital of the University of Basel, Switzerland
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    • Both authors contributed equally.

  • Dominikus Bönsch,

    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
    2. Psychiatric Hospital Rickling, Germany
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  • Otto Schmid,

    1. Division of Substance Use Disorders, Psychiatric Hospital of the University of Basel, Switzerland
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  • Johannes Kornhuber,

    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
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  • Stefan Bleich,

    1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
    2. Department of Psychiatry, Social-Psychiatry and Psychotherapy, Section Medicine, University of Hannover (MHH), Germany
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  • Gerhard A. Wiesbeck

    1. Division of Substance Use Disorders, Psychiatric Hospital of the University of Basel, Switzerland
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Kenneth M. Dürsteler-MacFarland, Psychiatric Hospital of the University of Basel, Wilhelm Klein-Strasse 27, CH-4012 Basel, Switzerland. E-mail: kenneth.duersteler@upkbs.ch

ABSTRACT

Research suggests that alpha-synuclein (SNCA) and NACP-Rep1, a polymorphic complex microsatellite repeat ~10 kb upstream of the SNCA gene translational start, may be involved in substance-use behaviors and craving. This study was the first to examine the effects of diacetylmorphine (DAM) on peripheral SNCA protein expression along with craving in opiate-dependent patients and to compare their NACP-Rep1 allele lengths with those of healthy controls. Using an experimental design, opiate-dependent patients on injectable heroin maintenance were investigated at four time points, twice pre- and post-injection of DAM. SNCA protein levels of 30 DAM-maintained patients were measured using enzyme-linked immunosorbent assay. Participant-rated effects were assessed in 42 patients by Tiffany's Heroin Craving Questionnaire (HCQ), Gossop's Short Opiate Withdrawal Scale and Visual Analogs. NACP-Rep1 alleles of 42 patients and 101 controls were analyzed. One-way repeated-measures ANOVAs provided significant overall effects for SNCA protein content (P = 0.028), craving (P < 0.001), withdrawal symptomatology (P < 0.001) and mood (P < 0.001), indicating that DAM injections may not only reduce craving but also SNCA protein expression. However, there was no association between protein expression and craving. Relative to controls, patients had significantly longer NACP-Rep1 alleles (P < 0.001). NACP-Rep1 allele lengths correlated positively with HCQ total scores averaged across all time points (r = 0.420; P = 0.006) as well as with post-DAM HCQ total scores in the morning (r = 0.488, P = 0.001) and afternoon (r = 0.423, P = 0.005). The findings provide evidence of a contributory role of SNCA and NACP-Rep1 for opiate dependence.

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