Objective: To begin to understand phenotypic and mechanistic variation of related anxiety disorders. We examine 3 aspects: (1) the co-variation of the non-specific signs shared by separation anxiety, thunderstorm phobia, and noise phobia, and co-morbidity; (2) 22 dogs 5 years after entry into an FDA trial to assess the efficacy of clomipramine in separation anxiety; (3) assessment of behavioral and physiological phenotypes of dogs with separation anxiety, noise and thunderstorm phobia and reactivity, unaffected dogs, and 2 groups of colony dogs with related behavioral pathologies.

Results: Associations of diagnoses and associations of non-specific signs within and between diagnoses are non-random. The greater the number of signs that the patient has, the longer they have experienced the signs, and the greater the number of co-morbid diagnoses, the worse the outcome. Physiologic responses differ between the anxiety disorders, affected and unaffected dogs differ in their behavioral responses, and their physiological responses suggest the existence of endophenotypes.

Conclusion: The co-morbidity of anxiety disorders in dogs and with the non-specific signs shared by them is important for treatment and outcome. Endophenotypes enhance the potential for gene-mapping and comparison of mechanism at the neurochemical level.

Novartis Animal Health and Pfizer provided funds for various parts of the studies contributing to this paper.