Preliminary evidence that reactivity to uncertain threat is an endophenotype for alcohol use disorder

•Exaggerated reactivity to uncertain threat may be an endophenotype for alcohol use disorder (AUD).•This was tested by comparing groups of individuals at various stages of AUD.•The at-risk, current and remitted AUD groups all displayed exaggerated reactivity.•Exaggerated reactivity to uncertain threat is present regardless of AUD status.•Reactivity to uncertain threat is a promising endophenotype for AUD.

BackgroundHaving an exaggerated reactivity to threats that are uncertain (U-threat) may facilitate the initiation and maintenance of excessive alcohol use in some individuals. This abnormality may not just be a concomitant for alcohol use disorder (AUD), but also an endophenotype for AUD.MethodThe aim of the current study was therefore to provide a preliminary test of whether U-threat is an endophenotype for AUD using several of the endophenotype criteria outlined by Gottesman and Gould (2003). Specifically, the study examined whether heightened U-threat reactivity is evidenced in those with: 1) current AUD; 2) remitted AUD (early and sustained remission examined separately); and 3) at-risk for AUD by virtue of having a positive family history of AUD. Participants (N = 147) completed a well-validated threat-of-shock task and startle eyeblink potentiation was collected as an index of aversive responding. Individuals and all available first-degree family members were diagnosed using structured clinical interviews.ResultsIndividuals at-risk for AUD, with current AUD, and AUD in remission (both early and sustained) all displayed exaggerated reactivity to U-threat, but not predictable threat, compared with non-AUD controls. Moreover, there were no significant differences between the at-risk and any of the AUD groups indicating that exaggerated reactivity to U-threat is relatively state-independent and present regardless of current AUD disease status.ConclusionsThe findings together highlight that exaggerated reactivity to U-threat may be a promising endophenotype for AUD that can aid in the refinement of mechanistic AUD disease models.