Neurobiologische Grundlagen der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung

Zusammenfassung

Bei der ADHS handelt es sich um eine multifaktoriell bedingte Störung, bei der die spezifischen neurobiologischen Ursachen bislang unbekannt sind. Die Monoamin-Defizithypothese hält eine Dysbalance von Dopamin, Noradrenalin und Serotonin für wahrscheinlich. Pathophysiologische Modellvorstellungen der ADHS postulieren dysfunktionale frontostriatale und frontozerebelläre Regelkreise, die sich durch bildgebende Befunde bestätigen lassen. Die strukturellen und funktionellen Auffälligkeiten sind bei Patienten mit ADHS jedoch bedeutend weitreichender, sodass heutzutage zahlreiche zentralnervöse Dysfunktionen das Erscheinungsbild der ADHS mitbedingen und insgesamt von einer Dysregulation funktioneller Konnektivität gesprochen werden muss. Die verfügbaren Tiermodelle der ADHS erlauben zwar, Rückschlüsse auf die Rolle einzelner Hirnstrukturen, auf die Funktion potenzieller Risikogene oder auf die pharmakologische Wirksamkeit bestimmter Medikamente zu ziehen, allerdings tragen sie bislang nicht zum besseren Verständnis ätiologischer Mechanismen bei. Bisher unternommene Versuche, konkrete Suszeptibilitätsgene mit genomweiter Signifikanz bzw. Risikoallele bestimmter genetischer Marker einwandfrei zu identifizieren, blieben bisher erfolglos. Vermehrt setzt sich die Vorstellung durch, dass die ADHS eine entwicklungsbiologische Störung darstellt, deren Verursachung allenfalls durch das Zusammenwirken multipler genetischer Variationen erklärbar ist. Angesichts des vielfältigen und heterogenen Phänotyps lassen sich etwaige Assoziationen mit den zugrunde liegenden Genotypen nur schwer abbilden. Daher empfiehlt es sich, valide (z. B. neuronale oder neuropsychologische) Endophänotypen zu definieren. Aus der neurobiologischen Forschung lassen sich gegenwärtig kaum therapeutische Implikationen ableiten.

Abstract

The origin of ADHD is multifactorial and both the aetiology and pathophysiology of ADHD are as yet incompletely understood. The monoamine deficit hypothesis of ADHD postulates a dysbalance in the interaction of the neurotransmitters dopamine, noradrenaline and serotonin. Pathophysiological mechanisms involved in ADHD include alterations in fronto-striatal circuits. The currently proposed animal models of ADHD are heterogeneous with regard to their pathophysiological alterations and their ability to mimic behavioural symptoms and to predict response to medication. Some evidence points to a genetic basis for ADHD which is likely to involve many genes of small individual effects. In summary, specific neurobiological substrates of ADHD are unknown and multiple genetic and environmental factors appear to act together to create a spectrum of neurobiological liability.

Schlüsselwörter

Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung - ADHS - Neurobiologie - Pathophysiologie - Genetik - Tiermodelle

Key words

attention deficit hyperactivity disorder - ADHD - neurobiology - pathophysiology - genetics - animal models

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