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


Gerlach, Manfred; Sharma, Manu; Romanos, Marcel; Lesch, Klaus-Peter; Walitza, Susanne; Conzelmann, H Annette; Krüger, Rejko; Renner, Tobias J (2019). Family-based association study on functional α-synuclein polymorphisms in attention-deficit/hyperactivity disorder. ADHD Attention Deficit and Hyperactivity Disorders, 11(1):107-111.

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, p = 1 p = 1) and rs356219 (OR 1.28; p = 0288) in affected siblings. However, a subanalysis on trios with index children showed a nominal association of rs356219 with ADHD (OR 1.43, p = 0.020), which survived Bonferroni correction (p = 0.039); again, no association for NACP-Rep1 (OR 0.8, p = 0.317, p = 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.

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, p = 1 p = 1) and rs356219 (OR 1.28; p = 0288) in affected siblings. However, a subanalysis on trios with index children showed a nominal association of rs356219 with ADHD (OR 1.43, p = 0.020), which survived Bonferroni correction (p = 0.039); again, no association for NACP-Rep1 (OR 0.8, p = 0.317, p = 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Department of Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Social Sciences & Humanities > Clinical Psychology
Health Sciences > Psychiatry and Mental Health
Language:English
Date:1 March 2019
Deposited On:23 Apr 2019 13:12
Last Modified:15 Apr 2020 23:40
Publisher:Springer
ISSN:1866-6116
OA Status:Closed
Publisher DOI:https://doi.org/10.1007/s12402-019-00286-8
PubMed ID:30927235

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