Early Life Adversity and Neuropsychiatric Disease: Differential Outcomes and Translational Relevance of Rodent Models

Abstract

It is now well-established that early life adversity (ELA) predisposes individuals to develop several neuropsychiatric conditions, including anxiety disorders, and major depressive disorder. However, ELA is a very broad term, encompassing multiple types of negative childhood experiences, including physical, sexual and emotional abuse, physical and emotional neglect, as well as trauma associated with chronic illness, family separation, natural disasters, accidents, and witnessing a violent crime. Emerging literature suggests that in humans, different types of adverse experiences are more or less likely to produce susceptibilities to certain conditions that involve affective dysfunction. To investigate the driving mechanisms underlying the connection between experience and subsequent disease, neuroscientists have developed several rodent models of ELA, including pain exposure, maternal deprivation, and limited resources. These studies have also shown that different types of ELA paradigms produce different but somewhat overlapping behavioral phenotypes. In this review, we first investigate the types of ELA that may be driving different neuropsychiatric outcomes and brain changes in humans. We next evaluate whether rodent models of ELA can provide translationally relevant information regarding links between specific types of experience and changes in neural circuits underlying dysfunction.

The estrous cycle modulates early-life adversity effects on mouse avoidance behavior through progesterone signaling

“…Efforts to understand how ELA affects the brain at the cellular and circuit levels in the service of vulnerability have involved the use of multiple animal models. Different mouse models of ELA have been shown to produce different behavioral phenotypes [25][26][27] , similar to human studies showing that different kinds of childhood maltreatment differentially predispose individuals to certain neuropsychiatric conditions [27][28][29][30] . Operationalizing anxiety in the mouse can be problematic given the psychological aspects of anxiety in humans that involve conscious awareness 31 .…”

The effects of childhood maltreatment on cortical thickness and gray matter volume: a coordinate-based meta-analysis

“…The human brain is a highly plastic organ, regulated by genes, but also shaped by environmental factors (Lim, Radua, & Rubia, 2014). Translational animal model also disclosed certain effects of early life adversity on neurodevelopment, indicating the susceptibility of brain structure (Aksić et al, 2013; Penninck et al, 2021; Waters & Gould, 2022). Early interventions were meaningful for preventing the psychosocial impairment of childhood maltreatment.…”

Brain network changes in adult victims of violence

“…In addition, the heterogeneity of the type of violence individuals were exposed to was large and the size of the sample did not allow us to test in network changes may differ depending on specific forms of violence such as (exclusively social) or non-social forms of violence. As pointed out in a recent review ( 38 ) physical and sexual violence in early childhood may seems to be associated with higher risks of PTSD and personality disorders while emotional violence more often associated with developing major depression. Animal models of physical versus non-physical abuse even suggest that brain circuit changes associated with abuse may differ.…”

“…Many studies have focused on physical, sexual or emotional abuse experienced during childhood ( 34 ), underlining the role of the hippocampus and amygdala ( 17 , 35 – 37 ). Furthermore, in populations that experienced violence in early childhood, physical forms of violence seem to be associated more strongly with changes in amygdala and anterior cingulate cortex while emotional abuse may result in changes related to reward and mood processing circuits ( 38 ). Other findings may even suggest differences in the brain networks of individuals exposed to emotion abuse versus neglect ( 39 ).…”