1st Faculty of Medicine Charles University 1st Faculty of Medicine Charles University Department of Psychiatry
msust 20.01.2011

Genetic, biochemical and other biological aspects of ADHD children

Research Area

  Addictions     Anxiety Disorders    Mood Disorders   Genomics   Psychopharmacology

  Eating Disorders    Psychophysiology    Neurodegenerative disorders                                     

 Cognitive Neuroscience    Schizophrenia    Traumatic stress

Research project name:

Genetic, biochemical and other biological aspects of ADHD children (6-11 age) include bio rhythms of melatonine. (IGA CR NR 9534-3/2007)

Project Leader:

Assoc. prof. Ivo Paclt, MD, PhD. Psychiatric Department 1st medical faculty

People Involved:

Assoc. prof. Ivo Paclt, MD, PhD. Prof. Petr  Zvolský, MD, DSc. Prof. Helena Illnerová, RDr.DSc  Prof.Milan Macek MD, DSc. Marta Kopečková, Mgr., Alena Sumová, RDr., DSc. Veronika Zagatová MD Ivan Hájek RDr, DSc

 Short project description:

ADHD (attention deficit hyperactivity disorder) is one of the most frequently diagnosed syndromes in the child psychiatry. The incidence is between 3 and 6 per cent of the children population; with boys predominating over girls at a ratio of 3:1 or more (Anderson et al.,1987). The key symptoms - inattentiveness, impulsivity and hyperactivity - deteriorate the relationship of these children both in the family and with their contemporaries, thus increasing the risk of social isolation. Hyperkinetic disorder (ICD-10 – International Classification Disorders, WHO, 1992) is a narrower diagnosis, and a subgroup of ADHD DSMIV diagnostic criteria, APA (American Psychiatric Association) 1994. Concordance rates of monozygotic vs. dizygotic hyperkinetic twin pairs were between 50 and 80% for monozygotic twins and between 0 and 33% for dizygotic twins (Stevenson,1992, Hechtman,1994, Thapar et al.,1995). The heritability of ADHD varies between 0.75 and 0.98, which is highly significant for genetic aetiology of ADHD. (Edelbrock et al.,1995). Our proposal project is based on genetic, biochemistry and MRA researches in our centres (Paclt et al., 2004; Paclt et al., 2005; Uhlíková et al., 2006 in press). ADHD children researches present consistent results in several candidate genes: DRD4, DAT, DRD5, DBH, 5HTT, HTR 1B a SNAP 25. (Faraone, 2005). In biochemistry studies are plasma level of MHPG decreased and plasma HVA activity elevated. MHPG level is elevate in children with comorbid disorders. In ADHD children is decrease 5HT level and it is more prominent in comorbid conduct disorder. DBH is decrease in ADHD and comorbid conduct disorder. We conclude that these biochemistry markers are potentially usefulness for identification groups for genetically analyses (Paclt et al., 2005). Authors especially interested in DBH plasma activity and identified developmental characteristics (norms) for various age in child hood and adolescents. We plan in cooperation with prof. Illnerová group study of biorhythms in ADHD children. Authors plan follow studies of prof. Illnerová rhythm of melatonin (3 hours period) in 40 ADHD children and 40 controls. (24 hours rhythms melatonin in saliva.) Project proposal: This project connects to last author’s papers. Authors want examine 130 ADHD children and their family members (age children 6-11). Genetic examination will realised in parents and siblings ADHD children. Diagnoses DSMIV and ICD10 (hyperkinetic disorder) will done by two independent psychiatrists. Scales Conners and Wender will also use for this examination. For diagnose ADHD will important imperative Conners deviation 2 sigma. In 40 children will examine DBH, 5HT, MHPG, HVA by Nagatsu and HPLC use. We will exam these polymophisms: DRD2 (Taq A1, RFLP for TaqI); DRD3 (Ba/I, RFLP Ser9Gly substitution); DRD4 (48-bp, VNTR 2-11 repeat segment 48-bp); DRD4 (521C/T, RFLP); DRD5 ((GT)n, VNTR repeat dinukleotid GT); DAT1 (40-bp, VNTR repeat segment 40-bp); 5-HTT (5HTTLPR, VNTR 20-23 bp repeat segment). DBH TaqB1 (polymorphism VNTR) 20-23 bp repeat segment localization 5,- end) DBH polymorphism (GT)n, G444A,G, Ala304Ser(G910T), C-1021T, (CA)n, 19bp insertion/deletion. (All polymorphisms will exam in all subjects-children and adults.) Genetic examination will complete by bucal irrigation analyses.

Authors present follow hypotheses 1) Polymorphisms these genes are often in ADHD family, like in children and in other members their families. 2) Low serotonin correlate to aggressively symptoms in Conners scale and DRD4 polymorphism. 3) Low DBH activity correlate to polymorphism DBH and prenatal hypoxia. 4) Patterns of melatonin/24 hours are different in 40 ADHD children and control group healthy children. 5) Theses differences in melatonine rhythms will collerate to polymorphism genes of ADHD children.

 

Project goals:

Analyses of genetic aetiology of ADHD, correlation to biochemistry and biorhythms of melatonin and possible correlation to the pharmacological therapy.

 

 Project Milestones, Timing: Projects is proposal for years 2007 – 2011.

 

 Possible Cooperation Mode: More possibilities, after future communication. 

 data gathering : possible replication study

 data analysis : include data analysis of replication study

 project management : cooperation in standardisation of inclusion and exclusion criteria’s 

 Publications:

Paclt I, Koudelova J Changes of dopamine-beta-hydroxylase activity during ontogenesis in healthy subjects and in an experimental model (Rats). Physiological Research; 2004; 53: 661-667. IF: 1.140

Paclt I, Koudelova J, Krepelova A, Uhlikova P, Gazdikova M, Bauer P, Biochemical markers and genetic research of ADHD. Neuroendocrinology Letters; 2005; 26: 423-430 IF: 1.048

Kopečková M, Paclt I, Goetz P Polymorphisms and low plasma activity of Dopamine-beta-hydroxylase in ADHD children. Neuroendocrinology Letters; 2006; 27: 748-754 IF: 1.005

Uhlíková P, Paclt I, Vaněčková M, Morcinek T, Seidel Z, Krásenský J, Daneš J Asymmetry of basal ganglia in children with attention deficit hyperactivity disorder. Neuroendocrinology Letters; 2007; 28: 604-609 IF: 0.924

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