Bundling the haystack to find the needle: Challenges and opportunities in modeling risk and resilience following early life stress

Abstract

Various forms of early life adversity (ELA) have been linked with increased risk for negative health outcomes, including neuropsychiatric disorders. Understanding how the complex interplay between types, timing, duration, and severity of ELA, together with individual differences in genetic, socio-cultural, and physiological differences can mediate risk and resilience has proven difficult in population based studies. Use of animal models provides a powerful toolset to isolate key variables underlying risk for altered neural and behavioral maturational trajectories. However, a lack of clarity regarding the unique features of differing forms of adversity, lab differences in the implementation and reporting of methods, and the ability compare across labs and types of ELA has led to some confusion. Here, we highlight the diversity of approaches available, current challenges, and a possible ways forward to increase clarity and drive more meaningful and fruitful implementation and comparison of these approaches.

Early Life Trauma Has Lifelong Consequences for Sleep And Behavior

“…The developmental trajectory of this adversity is not necessarily linear: fear learning is enhanced in both infancy and adulthood but attenuated during adolescence 41 . While each paradigm of early life adversity produces a unique outcome and developmental trajectory, there is a consistent finding of ubiquitous neurobehavioral effects and nonlinear developmental trajectory 48,53,70,71 . Thus, as we integrate the present sleep results into the early-life trauma literature in rodents and attempt to translate across species, we suggest that the disrupted sleep induced by early life trauma introduces a continued adversity that potentially amplifies trauma effects across the life span.…”

“…Our study highlights trauma with the caregiver in a rodent model, which complements the myriad other infant experience models. These models range from assessing early life stress experienced by variations of typical maternal care 72 , to models involving adversity, including the maternal separation/deprivation model (prolonged removal of maternal sensory stimulation of pups), exposure to trauma (shock or elevated stress hormones), brief novelty exposure outside the nest, and handling 19–21,28,29,35–37,40,53,71,73–76 . It should be noted that various labs have employed variations of the low bedding paradigm 77 , including a version using a wire-mesh floor, the present model is a milder version in which pups gain weight normally and reach normal developmental milestones 78 .…”

The Developmental Origins of Opioid Use Disorder and Its Comorbidities

“…In animal studies, several different models of ELA have been used to isolate the effects of adversity on brain development from other genetic and environmental variables. These methods, such as maternal separation (MS), limited bedding and nesting (LBN), fostering by abusive caregivers, and others, have been extensively described elsewhere (Molet et al, 2014 ; Doherty et al, 2017 ; Walker et al, 2017 ; Wakeford et al, 2018 ; Brenhouse and Bath, 2019 ). In rodents and non-human primates, numerous studies have demonstrated that ELA results in behavioral phenotypes that suggest underlying dysfunction in reward-related brain regions (Molet et al, 2014 ; Andersen, 2015 , 2018 ; Wakeford et al, 2018 ; Bonapersona et al, 2019 ; Birnie et al, 2020 ).…”

Limited Bedding and Nesting Induces Maternal Behavior Resembling Both Hypervigilance and Abuse

“…Deviations in the quality of parental care can come in a variety of forms, including multiple forms of abuse, neglect, anxious parenting and/or the loss of a caregiver. While it has been established that the accumulation of these and other forms of early life adversity (ELA) can increase the risk for a variety of forms of negative outcomes (Felitti et al, 1998; Brenhouse and Bath, 2019), how the different forms of altered parental care may confer unique risk for different forms of psychopathology are poorly understood.…”