Animal Models of Developmental Psychopathology

Abstract

In the last decade much progress has been made in research using animal models of developmental psychopathology. The field has moved from the demonstration of long‐term impacts of early adversity on behavioral and physiological development and the role of genetic risks for vulnerability, to including transgenerational transmission of stress‐induced phenotypes through epigenetic modifications. Additional and critical paradigm shifts have also taken place, including increased focus on ecologically and ethologically valid animal models, research on resilience, the adolescent transition as a period of brain and behavioral reorganization, and sex differences. In this chapter we review recent literature using rodent and nonhuman primate animal models that examines the biological mechanisms through which the early environment programs neurobehavioral, cognitive, and physiological development. We discuss the evolutionary role of this plasticity on behavioral development, as it has an adaptive value in changing environments. Because of maternal care's critical role in early environment, we focus on models that study the effects of mother–infant relationship disruption and dissect the mechanisms by which maternal care regulates the development of brain circuits that control emotional and social behaviors of relevance for developmental psychopathology. Finally, we discuss developmental sensitive/critical periods as windows of opportunity for plastic adaptation of developing organisms to the environment that, if taken too far—as in the case of early traumatic experiences such as childhood maltreatment—lead to maladaptive developmental trajectories (psychopathology, pathophysiology). Animal models of early life adversity are paramount to understand the basic mechanisms and principles that translate early experience into developmental outcomes in our own species.

Incorporating epigenetic mechanisms to advance fetal programming theories

“…A large rodent literature focusing on rats and mice and has extensively examined the effects of both prenatal and postnatal stress exposures on development (reviewed in Howell, Neigh, & Sanchez, 2016). Much of this work focuses on observing or manipulating the powerful dam-pup relationship (e.g., maternal separation).…”

Beyond Risk and Protective Factors: An Adaptation-Based Approach to Resilience

“…Much of what is known about the effects of early life stress on development comes from a vast rodent literature reported in over 6,000 peer-reviewed research articles extending over a century (reviewed in Howell, Neigh, & Sanchez, 2016). The large majority of this work has been conducted with rats and mice and has extensively examined the effects of both prenatal and postnatal stress (Howell et al, 2016). Much of the postnatal work focuses on observing or manipulating the powerful dam-pup relationship (e.g., maternal separation).…”

Developmental outcomes of early adverse care on amygdala functional connectivity in nonhuman primates

“…Poor maternal care in the form of infant maltreatment, including abuse and rejection, occurs in NHP species spontaneously and with prevalence rates similar to humans’ (2%–5%) (Brent, Koban, & Ramirez, 2002; Johnson, Kamilaris, Calogero, Gold, & Chrousos, 1996; Maestripieri & Carroll, 1998; Sanchez, 2006; Troisi & D'Amato, 1984). Developmental consequences include chronic activation of stress response systems and alterations in socioemotional functioning (Bramlett et al, 2017, 2018; Brent et al, 2002; Drury et al, 2017; Howell, Neigh, & Sánchez, 2016; Johnson et al, 1996; Maestripieri & Carroll, 1998; Morin, Howell, Meyer, & Sanchez, 2019; Sanchez, 2006; Sanchez, Hearn, Do, Rilling, & Herndon, 1998; Troisi & D'Amato, 1984). The naturalistic rhesus model of maternal infant maltreatment studied here is operationalized as both early life physical abuse and comorbid maternal rejection, both of which are associated with infant distress (Maestripieri, 1999; Maestripieri & Carroll, 1998; McCormack et al, 2009; McCormack, Sanchez, Bardi, & Maestripieri, 2006; Sanchez, 2006).…”