These findings led us to hypothesize that ANK3 expression might be linked to the prototypical human stress-response disorder, posttraumatic stress disorder (PTSD), which is defined, in part, by anhedonia and diminished interest following traumatic stress exposure. Additionally, we decided to investigate the relationship of ANK3 to disorders of the externalizing spectrum (e.g., antisocial personality and substance-related disorders) that have been linked to impulsivity, excessive reward-seeking, deficits in the ability to inhibit pre-potent behavioral responses and problems mediating conflicting action tendencies—traits that share similarities with behaviors observed in Ank3+/− mice (Krueger and South, 2009; Patrick et al., IN PRESS). We focused our analyses of externalizing on a latent variable representing a composite of disorders in the externalizing spectrum on the basis of prior evidence suggesting that this representation yields higher heritability estimates than any of the individual disorders within that spectrum, presumably because of the closer correspondence between the latent phenotype and its biological substrates (Wolf et al., 2010). Furthermore, numerous studies have found a high degree of comorbidity between PTSD and externalizing disorders. There is also evidence for both an
