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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.
This article was published in the following journal.
Name: Attention deficit and hyperactivity disorders
To date, only three polymorphisms (rs10830962, rs7754840 and rs1470579) are included in the genome-wide association study Catalog ( www.ebi.ac.uk/gwas ). However, the available evidence is limited in ...
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A synuclein that is closely related to ALPHA-SYNUCLEIN. It may play a neuroprotective role against some of the toxic effects of aggregated ALPHA-SYNUCLEIN.
A homolog of ALPHA-SYNUCLEIN that plays a role in neurofilament network integrity. It is overexpressed in a variety of human NEOPLASMS and may be involved in modulating AXON architecture during EMBRYONIC DEVELOPMENT and in the adult. Gamma-Synuclein may also activate SIGNAL TRANSDUCTION PATHWAYS associated with ETS-DOMAIN PROTEIN ELK-1.
A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
The diagnosis and treatment of human responses of individuals and groups to actual or potential health problems with the characteristics of altered functional ability and altered life-style. (American Nurses Association & Association of Rehabilitation Nurses. Standards of Rehabilitation Nursing Practice, 1986, p.2)
Attention deficit hyperactivity disorder (ADHD)
Attention deficit hyperactivity disorder (ADHD) is a group of behavioural symptoms that include inattentiveness, hyperactivity and impulsiveness. Attention deficit disorder (ADD) is a sub-type of ADHD - symptoms of ADHD include: a short attenti...
Parkinson's is a progressive neurological condition, affecting one person in every 500, 95% of which are over 40. It is caused by degeneration of more than 70% of the substantia nigra, which depletes the dopamine (the neurotransmitter involved in pro...