Genetik und Bildgebung bei Aufmerksamkeitsdefizit-/Hyperaktivitätsstörungen

S. Walitza; T. Renner; M. Romanos; L. Mecklinger; O. Tucha; M. Gerlach; K. W. Lange

doi:10.1055/s-0038-1626480

Nervenheilkunde, Table of Contents

Nervenheilkunde 2006; 25(06): 421-429
DOI: 10.1055/s-0038-1626480

Originaler Artikel

Schattauer GmbH

Genetik und Bildgebung bei Aufmerksamkeitsdefizit-/Hyperaktivitätsstörungen

Genetic and neuroimaging studies in attention deficit hyperactivity disorder

S. Walitza

¹Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und Psychotherapie, Universität Würzburg (Direktor: Prof. Dr. A. Warnke)

,

T. Renner

¹Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und Psychotherapie, Universität Würzburg (Direktor: Prof. Dr. A. Warnke)

,

M. Romanos

¹Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und Psychotherapie, Universität Würzburg (Direktor: Prof. Dr. A. Warnke)

,

L. Mecklinger

²Institut für Experimentelle Psychologie, Universität Regensburg (Direktor: Prof. Dr. K. W. Lange)

,

O. Tucha

²Institut für Experimentelle Psychologie, Universität Regensburg (Direktor: Prof. Dr. K. W. Lange)

,

M. Gerlach

¹Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und Psychotherapie, Universität Würzburg (Direktor: Prof. Dr. A. Warnke)

,

K. W. Lange

²Institut für Experimentelle Psychologie, Universität Regensburg (Direktor: Prof. Dr. K. W. Lange)

› Author Affiliations

Abstract

Zusammenfassung

Formalgenetische Untersuchungen zeigen, dass die Aufmerksamkeitsdefizit-/Hyperaktivitäts-Störung (ADHS) eine hohe Erblichkeit aufweist, wobei wahrscheinlich zahlreiche Gene mit jeweils moderatem Effekt beteiligt sind. Es werden die am häufigsten replizierten Befunde molekulargenetischer Studien zusammengefasst. Die Ergebnisse von bisherigen Genomscans ergeben Hinweise auf mehrere relevante Genorte, vorangestellt Chromosom 5p13, in dessen Nähe das Gen des Dopamintransporters (DAT1) lokalisiert ist. Assoziationsstudien zeigen Zusammenhänge zwischen Varianten in dopaminergen (DRD4, DAT1) bzw. serotonergen Genen (SERT) und dem Vorliegen einer ADHS. Neuroanatomische Hirnveränderungen bei ADHS finden sich vornehmlich im Bereich von fronto-striatalen Strukturen. Weiterhin treten weit verbreitet Auffälligkeiten in anderen kortikalen Arealen und dem Zerebellum auf. Funktionell-bildgebende Studien legen nahe, dass eine Dysfunktion frontostriataler Schleifen an der Pathophysiologie der ADHS beteiligt ist. Der Dopamintransporter ist ein wichtiges Element dopaminerger Neurotransmission; Neurorezeptorstudien zeigen eine erhöhte Dopamintransporter-Bindung radioaktiver Liganden bei ADHS sowie eine Reduktion dieser Bindung unter Methylphenidat-Behandlung.

Summary

Formal genetic and molecular genetic studies indicate that attention deficit hyperactivity disorder (ADHD) is highly heritable, involving multiple genes of moderate effect. Four genome-wide linkage studies and the most frequently reported positive results of association studies are reviewed. Linkage studies have detected chromosome 5p13 as a relevant region, which is in the vicinity of the location of the dopamine transporter gene (DAT1). The most frequently replicated findings in the candidate gene approach refer to polymorphisms in dopaminergic (DRD4, DAT1) and serotonergic genes (SERT). Neuroimaging studies show that ADHD involves structural brain abnormalities in fronto-striatal regions, other cortical regions and the cerebellum. Functional neuroimaging have implicated dysfunction of the fronto-striatal circuitry as likely contributing to the pathophysiology of ADHD. The dopamine transporter isa key regulator of dopamine. In vivo neuroreceptor imaging has shown increased dopamine transporter binding in ADHD anda decrease following methylphenidate treatment.

Schlüsselwörter

Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung - ADHS - Genetik - Bildgebung

Keywords

Attention deficit hyperactivity disorder - ADHD - genetics - neuroimaging

Full Text

References

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