Five hypothesized biological mechanisms linking adverse childhood experiences with anxiety, depression, and PTSD: A scoping review

Adults with symptoms of anxiety, depression, or PTSD and a history of adverse childhood experiences (ACEs) may experience more severe symptoms than those without ACEs. The identification of mechanisms linking ACEs to later mental health problems may provide salient treatment targets to improve outcomes. Several biological markers (cortisol, inflammation, allostatic load, DNA methylation, and telomere length) that are indicative of functional variation in stress response systems, have been hypothesized as potential mechanisms linking ACEs to later mental health outcomes. Much of the evidence supporting this hypothesis examines isolated pairwise associations between variables and it is unclear whether statistical tests of mediation support these conclusions. It is also unclear how much of the extant research has used theory to guide mediation analyses, which may be a salient factor in the recognition of a mechanism. This scoping review surveyed research conducting mediation analysis examining the indirect effect of any of these five biological markers on the relationship between ACEs and anxiety, depression, or PTSD. It further surveyed the use of theory in these analyses. Pubmed and seven electronic databases were searched: (1) APA PsychInfo (2) CINAHL Plus (3) Health Source: Nursing/Academic Edition (4) MEDLINE (5) Psychology and Behavioral Sciences Collection (6) Science and Technology Collection, and (7) SocINDEX. A total of 16 articles were identified. The majority of studies examined depression as an outcome and the statistical significance of indirect effects were mixed across mediators. Common theoretical models and frameworks were consistent with life course theory and evolutionary or developmental perspectives.