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Family-based association study on functional α-synuclein polymorphisms in attention-deficit/hyperactivity disorder

  • Manfred GerlachEmail author
  • Manu Sharma
  • Marcel Romanos
  • Klaus-Peter Lesch
  • Susanne Walitza
  • H. Annette Conzelmann
  • Rejko Krüger
  • Tobias J. Renner
Original Article

Abstract

Studies have strongly suggested a disturbed regulation of dopaminergic neurotransmission in attention-deficit/hyperactivity disorder (ADHD) and Parkinson’s disease (PD). A genetic and phenotypic overlap between both disorders is discussed. A well-studied risk gene for PD is the gene coding for α-synuclein (SNCA). α-Synuclein, a protein located primarily in the presynaptic vesicles, has been suggested to play a role in the modulation of dopamine transporter (DAT) function. DAT is the target of psychostimulants for the treatment of ADHD and plays a key role in regulating the dopamine concentrations in the synaptic cleft. In our sample consisting of German families with children affected by ADHD, we tested for association of allelic variants of two functionally relevant polymorphisms of the α-synuclein gene (NACP-Rep1: 156 families, 232 children; rs356219: 195 families, 284 children) with ADHD. Transmission disequilibrium test analysis revealed no over-transmission for NACP-Rep1 (OR 1, pnom = 1 padj = 1) and rs356219 (OR 1.28; pnom = 0288) in affected siblings. However, a subanalysis on trios with index children showed a nominal association of rs356219 with ADHD (OR 1.43, pnom = 0.020), which survived Bonferroni correction (padj = 0.039); again, no association for NACP-Rep1 (OR 0.8, p = 0.317, padj = 0.634) was found. In conclusion, we found in our pilot study a trend for an association of the rs356219 genotype in SNCA that may affect α-synuclein function and contribute to the aetiology of ADHD. In light of the small sample size of our study, the link between PD and ADHD through dopamine-related neurobiology warrants further investigations. Future studies on SNCA in large ADHD samples should focus on specified symptoms and traits, e.g. attentional capacities or emotional dysregulation.

Keywords

ADHD Dopamine transporter Alpha-synuclein Pathogenesis Parkinson’s disease 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Manfred Gerlach
    • 1
    Email author
  • Manu Sharma
    • 2
  • Marcel Romanos
    • 1
  • Klaus-Peter Lesch
    • 3
    • 4
    • 5
  • Susanne Walitza
    • 6
  • H. Annette Conzelmann
    • 7
  • Rejko Krüger
    • 2
    • 8
  • Tobias J. Renner
    • 7
  1. 1.Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental HealthUniversity Hospital of WürzburgWürzburgGermany
  2. 2.Center of Neurology and Hertie-Institute for Clinical Brain ResearchUniversity of TübingenTübingenGermany
  3. 3.Division of Molecular Psychiatry, Center of Mental HealthUniversity Hospital WürzburgWürzburgGermany
  4. 4.Laboratory of Psychiatric Neurobiology, Institute of Molecular MedicineSechenov First Moscow State Medical UniversityMoscowRussia
  5. 5.Department of Neuroscience, School for Mental Health and Neuroscience (MHeNS)Maastricht UniversityMaastrichtThe Netherlands
  6. 6.Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry ZurichUniversity of ZurichZurichSwitzerland
  7. 7.Department for Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyUniversity of TübingenTübingenGermany
  8. 8.LCSB, Luxembourg Centre for Systems BiomedicineUniversity of Luxembourg, Luxembourg and Centre Hospitalier de Luxembourg (CHL)Luxembourg CityLuxembourg

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