Zusammenfassung
Die Autoren geben eine Übersicht über den gegenwärtigen Wissensstand zur Genetik der Angsterkrankungen. Entsprechend der derzeitigen kategorialen Einteilung nach ICD-10 wird hierbei zwischen Panikstörung, generalisierter Angststörung, Phobien und posttraumatischer Belastungsstörung unterschieden. Einführend werden biologische Erklärungsmodelle auf der Grundlage von Pharmakotherapien, Provokationsuntersuchungen und Tier-Modellen referiert. Ausführlich werden die relevanten Befunde zur klinischen Genetik (Zwillings- und Familienstudien) und molekularen Genetik (Kopplungs- und Assoziationsuntersuchungen) dargestellt. Besonderen Raum nimmt hierbei die Beschreibung der Panikstörung ein, zu der die meisten Befunde vorliegen. Ergänzend werden die genetischen Befunde zu Angst als Persönlichkeitsdimension unter Berücksichtigung der aktuellen Endophänotypdiskussion zusammengefasst. Abschließend werden die ethische Problematik und therapeutische Relevanz der genetischen Forschung bei Krankheiten mit multifaktorieller und polygener Genese eingehend diskutiert.
Summary
The authors give an overview of the present state of knowledge on the genetics of anxiety disorders. According to ICD-10 or DSM III/IV classification, anxiety disorders comprise panic disorder, generalized anxiety, phobias, and post-traumatic stress disorder. In the context of the conceptual change from psychodynamic anxiety neuroses to complex, multifactorial anxiety disorders, a summary of biological hypotheses of the pathogenesis of anxiety derived from pharmacotherapy, challenge tests, and animal model disorders is provided. The relevant findings from clinical genetic studies (twin and family) and molecular genetic studies (linkage and association) are presented in detail. The most data now available are on panic disorder, though with regard to molecular genetics these are still preliminary. In addition, genetic findings on anxiety as a personality dimension are reviewed, taking into account the present phenotype discussion (category vs dimension). Finally, ethical and therapeutic implications of genetic research on complex, polygenic disorders are discussed.
Literatur
Arnold PD, Zai G, Richter MA (2004) Genetics of anxiety disorders. Curr Psychiatry Rep 6: 243–254
Boulenger JP, Uhde TW, Wolff EA, Post RM (1984) Increased sensitivity to caffeine in patients with panic disorder. Arch Gen Psychiatry 41: 1067–1071
Cloninger CR, Van-Erdewegh P, Goate A et al. (1998) Anxiety proneness linked to epistatic loci in genome scan of human personality traits. Am J Med Genet 81: 313–317
Deckert J, Catalano M, Syagailo YV et al. (1999) Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Hum Mol Genet 8: 621–624
Domschke K, Braun M, Ohrmann P et al. (2006) Association of the functional −1019C/G 5-HT1A polymorphism with prefrontal cortex and amygdala activation measured with 3 T fMRI in panic disorder. Int J Neuropsychopharmacol 9: 349–355
Domschke K, Ohrmann P, Braun M et al. (2007) Influence of the catechol-O-methyltransferase val158met genotype on amygdala and orbitofrontal cortex emotional processing in panic disorder. Psychiatry Res Neuroimaging (im Druck)
Finn DA, Rutledge-Gorman MT, Crabbe JC (2003) Genetic animal models of anxiety. Neurogenetics 4: 109–135
Hettema JM, Neale MC, Kendler KS (2001) A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 158: 1568–1578
Kendler KS, Karkowski LM, Prescott CA (1999) Fears and phobias: reliability and heritability. Psychol Med 29: 539–553
Klein DF (1964) Delineation of two drug responsive anxiety syndromes. Psychopharmacol 5: 397–408
Lesch KP, Bengel D, Heils A et al. (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274: 1483–1487
Maier W, Lichtermann D, Minges J, Heun R (1992) Personality traits in subjects at risk for unipolar major depression: a family study perspective. J Affect Disord 24: 153–163
Marks IM, Herst ER (1970) A survey of 1200 agoraphobics in Britain. Soc Psychiatry 5: 16–24
Rosenbaum JF, Biederman J, Hirshfield DR et al. (1991) Further evidence of an association between behavioral inhibition and anxiety disorders: results from a family study of children from a non-clinical sample. J Psychiatr Res 25: 49–65
Rowe DC, Stever C, Gard JM et al. (1998) The relation of the dopamine transporter gene (DAT1) to symptoms of internalizing disorders in children. Behav Genet 28: 215–225
Segman RH, Shalev AY (2003) Genetics of posttraumatic stress disorder. CNS Spectr 8: 693–698
Smoller JW, Acierno JS Jr, Rosenbaum JF et al. (2001) Targeted genome screen of panic disorder and anxiety disorder proneness using homology to murine QTL regions. Am J Med Genet 105: 195–206
Stein MB, Jang KL, Livesley WJ (1999) Heritability of anxiety sensitivity. Am J Psychiatry 156: 246–251
Van West D, Claes S (2004) The genetics of panic disorder: state of the art. Acta Neuropsychiatrica 16: 68–78
Zwanzger P, Deckert J (2007) Anxiety disorders: Causes, clinical picture and treatment. Nervenarzt 78: 349–360
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Domschke, K., Deckert, J. Genetik der Angsterkrankungen. Nervenarzt 78, 825–835 (2007). https://doi.org/10.1007/s00115-007-2315-z
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DOI: https://doi.org/10.1007/s00115-007-2315-z