D4 7 repeats allele
CHAPITRE 6 CONCLUSION GENERALE
Le TDAH est un trouble fréquent et très handicapant. L'étiologie génétique et l'implication de la dopamine dans le trouble ont mené à la recherche d'association entre les gènes dopaminergiques et le TDAH. Le DRD4-7R a reçu une attention particulière, mais les études concernant les caractéristiques cliniques sont toutefois peu nombreuses.
Cette étude avait pour but de caractériser le portrait comportemental et attentionnel des enfants atteints de TDAH et porteurs du DRD4-7R, comparés à des enfants atteints de TDAH, mais non-porteurs du polymorphisme, et ce, dans une population ethniquement homogène et cliniquement bien caractérisée.
Nous avons recruté une population ethniquement homogène puisque tous les enfants étaient canadiens-français sur trois générations (n = 137). Cliniquement, les enfants inclus dans l'étude devaient avoir à la fois un diagnostic de TDAH (selon le DSM-IV) posé par un médecin ou un pédopsychiatre et basé sur l'entrevue structurée du C-DISC-IV (version parents). Les échelles de Conners, version parent et enseignant, ainsi que la CBCL ont été utilisées afin d'évaluer les caractéristiques comportementales. Le test du NEPSY et le CPT ont permis d'analyser les caractéristiques attentionnelles. Les enfants ont été séparés en deux groupes selon leur génotype du DRD4. Nous avons ensuite utilisé le test non- paramétrique de Mann-Whitney pour comparer les deux groupes (avec ou sans le DRD4-
7R).
Nous avons observé que les enfants atteints de TDAH et porteurs de l'allèle DRD4- 7R ont plus de problèmes de comportement à l'échelle de Conners, version de l'enseignant, que les enfants également atteints de TDAH, mais non-porteurs du polymorphisme. Ce résultat confirme ceux d'autres études qui suggèrent que le DRD4-7R est associé à un comportement plus sévère. Les porteurs du DRD4-7R présentent toutefois une meilleure attention visuelle au NEPSY que les non-porteurs. La divergence avec les résultats de la littérature pourrait s'expliquer par l'utilisation de différents tests de mesure ainsi que l'hétérogénéité des caractéristiques des populations.
Cette étude présente des limites dont il faut tenir compte dans l'interprétation des résultats. Notre cohorte est relativement modeste (n =137). Il serait donc intéressant d'avoir
une plus grande cohorte afin de vérifier si ce portrait est conservé. Pour caractériser la composante comportementale, nous avons utilisé les échelles de Conners qui sont très utilisées en clinique. Par contre, les scores du NEPSY utilisés ne permettent peut-être pas de bien évaluer la composante attentionnelle due à la faible étendue des données possibles. D'autres tests neuropsychologiques auraient pu être utilisés pour étudier les autres composantes des fonctions executives ou motivationnelles.
Malgré les limites, les résultats de cette étude permettent d'augmenter les connaissances concernant l'effet du DRD4-7R sur le portrait clinique. Une meilleure compréhension du profil spécifique associé à un risque génétique en particulier (ici le DRD4-7R) nous permet d'approfondir nos connaissances concernant l'étiologie du trouble.
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ANNEXE
Critères diagnostiques selon le DSM-IV adaptés pour les enfants.
Hyperactivité/Impulsivité Inattention - Remue souvent les mains ou les pieds, ou se tortille
sur son siège
- Souvent, ne parviens pas à prêter attention aux détails, ou fais des fautes d'étourderie dans les devoirs scolaires ou d'autres activités
- Se lève souvent en classe ou dans d'autres situations où il est supposé rester assis
- A souvent du mal à soutenir son attention à l'école ou dans les jeux
- Souvent, cours ou grimpe partout, dans des situations où cela est inapproprié
- Semble souvent ne pas écouter quand on lui parle personnellement
- A souvent du mal à se tenir tranqu'Ue dans les jeux ou activités de loisirs
- Souvent, ne se conforme pas aux consignes et ne parviens pas à mener à terme ses devoirs scolaires ou ses tâches domestiques*
- Agis souvent comme s'il était « monté sur ressort » - A du mal à organiser ses travaux ou ses activités - Parle trop souvent - Souvent, évite ou fait à contrecœur les tâches qui
nécessitent un effort mental soutenu
- A souvent du mal à attendre son tour - Perds souvent des objets nécessaires à ses activités
- Laisse souvent échapper la réponse à une question qui n'est pas encore entièrement posée
- Souvent, se laisse facilement distraire par des stimuli externes
- Interromps souvent les autres ou impose sa présence - A des oublis fréquents dans la vie quotidienne *Quand cela n'est pas dû à un comportement d'opposition, ni à une incapacité à comprendre les consignes.