Shiloh Cleveland

Early life adversity (ELA), characterized by threat (experiences involving threat of harm), and not deprivation (absence of expected environmental inputs), has been associated with accelerated biological aging in youth. Although understanding of underlying processes is limited, heightened fear responding is a candidate. In 168 youth, we tested whether threat- and deprivation-related ELA were associated with fear responses across multiple levels of analysis and whether fear responses explained links of threat with accelerated biological aging (advanced pubertal stage and epigenetic age). Youth and caregivers reported on youths’ lifetime ELA experiences to compute threat and deprivation composites. Youth reported their pubertal maturation and provided saliva samples for epigenetic age estimation. Fear responses (indexed by skin conductance response [SCR], self-reported fear, and amygdala activation) were collected during a fear conditioning and extinction task (SCR, self-reported fear) and emotional stimulus viewing task (amygdala activation). Multilevel models revealed that greater threat was associated with impaired discrimination between danger and safety cues during conditioning based on self-report and during early extinction based on SCR. Greater deprivation related to enhanced danger-safety discrimination during late conditioning based on SCR. Additionally, only threat was associated with greater left amygdala activation to negative (vs. neutral) stimuli. No evidence of indirect effects was found linking threat with accelerated biological aging. Results suggest that threat-related ELA may correspond to heightened neural sensitivity to danger and reduced danger-safety discrimination, whereas deprivation-related ELA may enhance learning of danger vs. safety cues. Findings indicate potential differential associations between threat- and deprivation-related ELA and fear-related processes.

Multigroup cohort studies are used to compare exposed and unexposed groups on important outcomes. Recruitment for these studies can be done simultaneously or sequentially. When recruitment is simultaneous, there are many advanced statistical techniques, including propensity score matching, that can be used to select balanced groups to account for confounders of the effect of the exposure on the outcome. This paper presents a novel method for using propensity score matching for sequential recruitment using a five-step modular approach: (1) estimate propensity scores, (2) create propensity clusters, (3) match participants, (4) create holdout groups, and (5) enroll. These steps are repeated each recruitment period. We explain each step, providing R code to assist researchers in implementation, then demonstrate the performance of the method in a multigroup cohort study examining the effects of posttraumatic stress disorder on cardiovascular risk markers among trauma-exposed individuals. The method performed well and improved balance compared to using no selection technique, and it also performed similarly to propensity score matching with simultaneous recruitment. This method provides a novel approach to sequential recruitment in multigroup cohort studies. Future research should explore how more sophisticated methods for selecting covariates, generating propensity scores, and selecting matches could improve this method further.