Resilienz gegen Rückfall – protektive neuronale Mechanismen in der Alkoholabhängigkeit

Zusammenfassung

Als zentrale Aspekte der Alkoholabhängigkeit gelten eine veränderte Emotionswahrnehmung, –regulation und eine verminderte kognitive Fähigkeit zur exekutiven Verhaltenskontrolle. Auch das Zusammenspiel von genetischen und suchtrelevanten Persönlichkeitsfaktoren und der Hirnfunktion und –struktur werden verstärkt diskutiert. Die vorliegenden multimodalen Bildgebungsstudien sollten das Verständnis der neurobiologischen Grundlagen der Emotionsverarbeitung und Exekutivfunktionen in der Alkoholabhängigkeit erweitern, vor allem in Hinsicht auf mögliche Zusammenhänge zum individuellen Rückfallrisiko. Dafür wurden (prospektive) Untersuchungen mit alkoholabhängigen Patienten nach der Entgiftung, gesunden Erwachsenen und gesunden Jugendlichen durchgeführt, unter Verwendung von funktioneller und struktureller Magnetresonanztomografie sowie von Positronen-Emissions-Tomografie. Zusätzlich wurde bei den alkoholabhängigen Patienten das in früheren Studien beschriebene Rückfallrisiko-assoziierte GATA4- rs13273672-Gen bestimmt, um dessen Einfluss auf die funktionelle Alkoholreizverarbeitung und den Therapieverlauf zu prüfen. In diesen Studien konnten protektive Faktoren identifiziert werden, die vermutlich einem zukünftigen Rückfall entgegenwirken: 1) erhöhte Aktivierung des anterioren cingulären Kortex während der Verarbeitung negativer Emotionen; 2) flexible und kompensatorische Aktivierung neuronaler (präfrontaler) Ressourcen zur Bewältigung hoher kognitiver Ansprüche; 3) GATA4-Genotyp-abhängige Amygdala-Reaktivität auf Suchtreize; und 4) strukturelle Integrität der Frontalhirnareale, die sowohl mit der Verhaltenssteuerung als auch mit (suchtrelevanter) Impulsivität assoziiert sind. Somit geben diese Studienergebnisse wichtige Hinweise auf protektive neuronale Mechanismen in der Alkoholabhängigkeit, die Patienten nach der Entgiftung befähigen, auch angesichts schwieriger Situationen abstinent zu bleiben und kennzeichnen möglicherweise Faktoren und Hirnveränderungen erfolgreicher Therapieprozesse.

Abstract

Central aspects of alcohol dependence are an altered perception of emotion and regulation of negative mood as well as reduced cognitive control over executive functioning. Furthermore, the interaction between genetics and addiction-associated personality factors, on the one hand and brain function and structure, on the other are in the focus of interest. The present multimodal imaging studies aimed to gain further insights into the neurobiological basis of emotion processing and executive functions in alcohol dependence and to elucidate their role in increasing resilience against relapse. Therefore, we examined detoxified alcohol-dependent patients, healthy adults and adolescents using functional and structural magnetic resonance imaging, as well as positron emission tomography and associated the patients’ clinical development prospectively. Additionally, genotyping of GATA4 rs13273672, which had previously been associated with treatment outcome, was performed to test for potential genotype effects on alcohol cue-induced brain activity and relapse behavior. Our studies revealed protective mechanisms against relapse: 1) increased activation in the anterior cingulate cortex during emotion processing, 2) flexible activation of prefrontal resources when mastering high cognitive demands, 3) a GATA4-genotype-dependent high amygdala-reactivity elicited by alcohol cues, and 4) structural integrity of frontal brain areas implicated in reasoning, behavior control and trait impulsiveness. These results help to identify mechanisms contributing to resilience against relapse in alcohol dependence, which enable patients to remain abstinent despite stressful situations, and which may characterize factors or brain changes of successful therapeutic processes.

Schlüsselwörter

Bildgebung - Emotionsverarbeitung - Exekutivfunktionen - Alkoholabhängigkeit - Rückfall

Key words

imaging - emotion processing - executive functions - alcohol dependence - relapse

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