New insights into early-life stress and behavioral outcomes

Abstract

Adverse early-life experiences, including various forms of early-life stress, have consistently been linked with vulnerability to cognitive and emotional disorders later in life. Understanding the mechanisms underlying the enduring consequences of early-life stress is an active area of research, because this knowledge is critical for developing potential interventions. Animal models of early-life stress typically rely on manipulating maternal/parental presence and care, because these are the major source of early-life experiences in humans. Diverse models have been created, and have resulted in a wealth of behavioral outcomes. Here we focus on recent findings highlighting early-life stress-induced behavioral disturbances, ranging from hippocampus-dependent memory deficits to problems with experiencing pleasure (anhedonia). The use of naturalistic animal models of chronic early-life stress provides insight into the spectrum of cognitive and emotional outcomes and enables probing the underlying mechanisms using molecular-, cellular-, and network-level approaches.

Figure 1

A unifying theoretical framework for how early-life stress can induce long-term changes in behavior. The inciting event is the experience of early-life stress, represented in the first concentric circle. Early-life stress causes a cascade of changes acutely during the perinatal period that results in abnormal neuronal development and changes in gene expression, which are maintained long-term via epigenetic modifications of the chromatin (represented in the second concentric circle)[95,98,102]. These molecular- and cellular-level changes build upon each other to create altered synaptic connectivity and circuit development at the level of the network, ultimately resulting in the observed alterations in cognition, emotion, and pleasure/reward (represented by the 3 nodes within the third concentric circle)[78,93,103,104].