Imaging genetics of anxiety disorders.

Anxiety disorders are frequent and burdensome psychiatric diseases. Despite their moderate to strong heritabilities, the search for candidate genes has been limited by methodological shortcomings hitherto, e.g., the use of clinically defined, but neurobiologically heterogeneous categorical phenotypes. Investigating neurobiological response patterns associated with fear processing as an intermediate phenotype might aid in overcoming these difficulties. The existing imaging literature on the neurobiological correlates of fear processing and anxiety disorders points to a pivotal role of the amygdala in the human fear circuit. Therefore, amygdala responsiveness to anxiety-related stimuli was suggested as an intermediate phenotype for anxiety disorders. The present article provides an overview of imaging genetic studies investigating genetic effects on amygdala responsiveness with particular emphasis on recent imaging genetic findings in anxiety-related traits, panic disorder and social phobia. The existing studies consistently reveal strong genetic effects on the responsiveness of the fear circuit, particularly of genetic variants previously discussed as potential susceptibility variants for anxiety, e.g., the COMT 158val allele or the 5-HTTLPR short allele. Further research will be necessary involving larger sample sizes to allow for investigating gene-gene and gene-environment interactions. More evolved statistical and neuroimaging methods such as effective connectivity measures could lead to a better understanding of imaging endophenotypes and the nature of gene-brain relationships. Longitudinal studies in patient samples will be required to elucidate how genetically influenced neurobiological intermediate phenotypes are associated with subtype, severity and the course of anxiety disorders, thereby having the potential for developing individualized therapy regimes derived from neurobiological research. Copyright 2009 Elsevier Inc. All rights reserved.