La génétique

L'origine génétique du TDA/H fait partie des hypothèses courantes. Mais une tendance tempéramentale, voire une maladie peut dominer dans une lignée, sans faire appel uniquement au bagage génétique. Dans le cas type de la gémellité où la concordance est toujours plus grande, il n'en reste pas moins que le matrice génitrice fut la même et soumise aux conditions identiques de milieu, comme l'alimentation et le métabolisme propre de la mère, le phénomène de rejet immunitaire de la greffe foetale. Il est surprenant que l'aîné mâle souffre plus souvent de TDA/H (et autres maladies physiques) que la fille, même aînée ou les autre membres de la fratrie.

La vie se forme d'une myriade de facteurs, chaque individu purement unique dans sa constellation cérébrale. C

 
1: Ned Tijdschr Geneeskd. 2005 Jul 30;149(31):1726-9.  

[Hereditary factors in attention deficit hyperactivity disorder]
[Article in Dutch]
Fliers EA, Franke B, Buitelaar JK.
Universitair Medisch Centrum St Radboud, afd. Psychiatrie, Nijmegen.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by concentration problems, hyperactivity and impulsivity. Disturbances in dopamine and/or noradrenalin neurotransmission are probably the underlying pathophysiological mechanisms of ADHD. Around 80% of variants of the phenotype can be ascribed to hereditary factors. There are various chromosomal loci containing ADHD genes. They partially overlap the loci found in linkage studies on dyslexia and autism. It seems likely that a number of genetic variants, each with a small effect size, in combination with gene-environment interactions predispose to ADHD. There is a high degree of phenotypical heterogeneity among people with ADHD. Finding endophenotypes may improve the power of genetic studies. Endophenotypes are specific expressions of the underlying pathophysiology, intermediate between gene and phenotype. Neuro-imaging studies in children with ADHD have indicated abnormalities in frontostriatal, temporal and cerebellar volume. Unaffected brothers and sisters show the same cerebral abnormalities, but not the cerebellar abnormalities. These brain abnormalities together with specific neuropsychological features could be ADHD endophenotypes.

PMID: 16114287 [PubMed - in process]

2: Curr Psychiatry Rep. 2004 Apr;6(2):143-8.

 

Recent advances in the genetics of attention deficit hyperactivity disorder.
Kent L.
Developmental Psychiatry Section, University of Cambridge, Douglas House, 18 Trumpington Road, Cambridge CB2 2AH, UK. lk255@cam.ac.uk

In the past few years, interest in the molecular genetics of attention deficit hyperactivity disorder (ADHD) has grown enormously, with many groups searching for susceptibility genes, often through large collaborative efforts facilitated by the International ADHD Genetics Consortium. Association findings for several candidate genes within the dopaminergic system, the DRD4 and DRD5 receptor genes and the dopamine transporter gene, DAT1, have been well replicated, and the first of several ongoing genome linkage scan study results have been published. Current challenges in this field are to identify the actual functional variant(s) in these genes conferring susceptibility and other genetic and environmental risk factors for ADHD.
PMID: 15038917 [PubMed - in process]
 

 

3 : Am J Med Genet B Neuropsychiatr Genet. 2005 Jan 5;132(1):109-25.  

Molecular genetic studies of ADHD: 1991 to 2004.
Bobb AJ, Castellanos FX, Addington AM, Rapoport JL.

Child Psychiatry Branch, NIMH, NIH, 10 Center Drive, Bethesda, MD 20892, USA.

Attention deficit hyperactivity disorder (ADHD)is highly heritable but is likely a complex disorder involving multiple genes of moderate effect (Smalley [1997: Am J Hum Genet 60:1276-12821]). Over 100 studies have examined the genetics of ADHD by linkage or association, though no article has presented a comprehensive overview of all published reports. We reviewed all ADHD studies, including 3 genome-wide linkage studies, and association studies of 94 polymorphisms in 33 candidate genes. To simplify comparisons across heterogeneous articles, demographics and comorbidity were ignored; analyses of subtype and haplotypes were excluded; and only the most positive finding for each polymorphism in a study was reported. Thirty-six percent of all findings were positive (P< 0.05), 17% were trends (0.05 <P < 0.15), and 47% were negative (P > 0.15). Studies utilizing dimensional measures of ADHD tended to result in higher rates of positive findings than those using categorical diagnoses (X(2) = 5.6, P = 0.018), and case-control studies tended to result in higher rates of positive findings than family-based studies (X(2) = 18.8, P < 0.001). However, for either dichotomy, no significant difference remained when analyzing only studies using both methods within the same population and polymorphism. Evidence for association exists for four genes in ADHD: the dopamine D4 and D5 receptors, and the dopamine and serotonin transporters; others are promising but need further replication, including the dopamine D2 and serotonin 2A receptors. All candidate gene approaches continue to face the problem of relatively low power, given modest odds ratios for even the best replicated genes. Copyright 2004 Wiley-Liss, Inc.
PMID: 15700344 [PubMed - in process]