The authors then went on to look for the duplication in a set of 70 unrelated patients with phobias and found it in 68 subjects. This degree of association is one of the strongest reported for a psychiatric disorder

and a genetic polymorphism. There are, however, many questions that require further clarity, and which additional studies may answer. For example, what is surprising is the broad clinical classification of the anxiety disorders in the patients with the DUP25. From the description of Inhibitors,research,lifescience,medical the patients, one could assume that there is a common genetic predisposition to all types of phobia, which other studies do not support. The other surprising finding was the complete lack of linkage between the phenotype and DNA markers that flank or are contained within the duplication. Gratacòs et al10 explain this to be a result of the nonmendelian segregation of the duplication within Inhibitors,research,lifescience,medical families, since the segregation of the duplication in families is far from simple. Cases of de novo duplication, reversion from duplicated to nonduplicated chromosomes, and the apparent conversion from

one form of the duplication to another were all observed within families. The duplication also exhibits mosaicism, in that it is not present in all cells analyzed. The authors propose that the mechanism by which the 15q24-26 Inhibitors,research,lifescience,medical duplication leads to panic and phobic disorders and joint laxity is probably see more through a dosage effect, with the overexpression Inhibitors,research,lifescience,medical of one or several genes present in the duplicated region; however, we will have to await further studies to shed more light on this association. Animal models of anxiety A complementary approach to genetic studies of anxiety and related disorders in humans involves the investigation of genes and their protein products implicated in the Inhibitors,research,lifescience,medical brain neurocircuitry of fear

and anxiety in animal models. Anxiety is one of the psychiatric syndromes best suited to analogy with animal states. It is well understood that fear, escape, or avoidance behavior, and panic-like responses are ubiquitous throughout animal phylogcny, and as Gorman et ai74 have posited, it takes relatively little intuition to recognize that a rodent that avoids entering a cage in which adverse through stimulus has been presented in the past, emulates a phobic patient avoiding a situation that has previously elicited a panic attack. However, as the same authors caution,74 the analogy of panic attacks to animal fear and avoidance responses “is to be sure, imperfect.” Most animal models of anxiety states involve conditioning, and it is not at all clear that PD or any other anxiety disorder except PTSD involves prior exposure to any aversive stimulus. Nevertheless, there are many aspects of conditioned fear in animals that make the analogy with human phenotypes (eg, panic attacks) irresistible, and thus validate the pursuit of genetic studies in model animals.