Clinical and molecular-genetic markers of ADHD in children.
OBJECTIVE
The objective was to make a contribution to deepening the knowledge of the etiopathogenesis of ADHD.


METHODS
In an association study design, an analysis of polymorphisms of selected genes was conducted in 119 hyperkinetic boys and a control group of boys, aged 7-13. Furthermore several psychologically determined subgroups were identified. A connection between psychological functions (endophenotypes) and genes were looked for.


RESULTS
There was a statistically significant difference found in allelic and genotype frequencies of the TaqI A polymorphism of the DRD2 gene. The frequency of the allele A1 in hyperkinetic boys and the control subjects was 0.26 and 0.15, respectively (p<0.003). A statistically significant occurrence of atypical genotypes (8/10, 7/10 and 10/11) of the DAT1 gene was also found in hyperkinetic boys and a connection between the M235 polymorphism of the angiotensinogene gene and the positive family history of psychiatric illness was found in probands (p=0.031). Significant correlations between the results of some neuropsychological tests and genes for neuro-/immunomodulators (IL-6, TNF-alpha) and the gene for the brain-derived neurotrophic factor (BDNF) were found.


CONCLUSIONS
The study showed a statistically significant prevalence of A1 allele of the DRD gene in the hyperkinetic group. We also found a significantly higher incidence of atypical DAT genotypes in the hyperkinetic group. Furthermore we found significant connections with particular gene polymorphisms which may hypothetically represent a neurodevelopmental risk factor in the etiopathogenesis of the disorder (IL-2, IL-6, TNF-alpha, BDNF). We further found a connection of the M235 polymorphism of the AGT (angiotensinogene) gene to positive family history of psychiatric illness (p=0.031). As for cognitive characteristics, we identified three subtypes with different cognitive performance profiles. This finding shows interindividual variability of cognitive style in the group of hyperkinetic boys.
Drtilkova
Ivana
I
Department of Psychiatry, Faculty Hospital and Masaryk University Brno, Czech Republic. idrtilkova@fnbrno.cz
Sery
Omar
O
Theiner
Pavel
P
Uhrova
Alena
A
Zackova
Marketa
M
Balastikova
Blanka
B
Znojil
Vladimir
V
D000293:Adolescent; D001288:Attention / Q000187:drug effects / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D015415:Biomarkers; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D002648:Child; D018153:Czech Republic / Q000453:epidemiology; D004192:Discrimination, Psychological / Q000502:physiology; D005556:Form Perception / Q000502:physiology; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use; D009483:Neuropsychological Tests; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000235:genetics
D015415:Biomarkers; D000697:Central Nervous System Stimulants; D005819:Genetic Markers; D017448:Receptors, Dopamine D2; D008774:Methylphenidate