Early life adversity during the infant sensitive period for attachment: Programming of behavioral neurobiology of threat processing and social behavior

Abstract

Animals, including humans, require a highly coordinated and flexible system of social behavior and threat evaluation. However, trauma can disrupt this system, with the amygdala implicated as a mediator of these impairments in behavior. Recent evidence has further highlighted the context of infant trauma as a critical variable in determining its immediate and enduring consequences, with trauma experienced from an attachment figure, such as occurs in cases of caregiver-child maltreatment, as particularly detrimental. This review focuses on the unique role of caregiver presence during early-life trauma in programming deficits in social behavior and threat processing. Using data primarily from rodent models, we describe the interaction between trauma and attachment during a sensitive period in early life, which highlights the role of the caregiver's presence in engagement of attachment brain circuitry and suppressing threat processing by the amygdala. These data suggest that trauma experienced directly from an abusive caregiver and trauma experienced in the presence of caregiver cues produce similar neurobehavioral deficits, which are unique from those resulting from trauma alone. We go on to integrate this information into social experience throughout the lifespan, including consequences for complex scenarios, such as dominance hierarchy formation and maintenance.

Keywords: Amygdala; Development; Dominance hierarchy; Social behavior; Threat.

Fig. 1

Transitions in learning across early development. Using a fear conditioning paradigm of odor-shock presentations has enabled us to uncover a developmentally unique learning system in pups that typically supports attachment learning. Data indicate that during the sensitive period for attachment learning (PN < 9), low CORT levels block amygdala plasticity to prevent pups from learning amygdala-dependent fear/threat. Instead, this learning paradigm activates the attachment learning neural circuit involving elevated NE (thick gray arrow) to produce approach responses to the odor (Moriceau et al., 2006). The odor also takes on qualities of the maternal odor to support nipple attachment and enhance prosocial behaviors to the mother. In pups older than PN9, this fear conditioning paradigm accesses the amygdala to support fear/threat learning if the pup is alone. A critical feature of this learning is that shock induces activation of the HPA axis and CORT release, which is necessary for the young amygdala to learn. However, if the mother is present, she socially buffers the pup’s stress response, and pups revert to sensitive period learning and learn an odor preference (red dashed line). This mother-controlled switch between fear and attachment learning is mediated through the mother’s ability to control pups CORT (Sullivan, in press). A more adult-like fear learning system, which cannot be switched on/off by CORT develops by PN15. Environmental variables that control pups’ CORT level, such as receiving CORT from a stressed mother via milk, environmental manipulations that increase pups’ CORT (abusive rearing) or the mother’s ability to socially buffer the pups (compromised in abusive mothers), have the potential to modify the age of these transitions and whether a pup learns fear or attachment (Moriceau et al., 2006, Perry and Sullivan, 2014, Raineki et al., 2012, Shionoya et al., 2007, Sullivan and Holman, 2010). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Timeline of attachment learning and the effects of early life maltreatment on later-life social and emotional behavior in the rat model of trauma associated with attachment. Early infants will learn attachment regardless of the quality of care, while slightly older infants (PN10-PN15) will either learn to fear a traumatic associated stimulus when away from the mother or learn an attachment if acquisition takes place with the mother. Testing later in life shows that only the early life trauma associated with attachment will lead to lifelong amygdala-dependent behavioral deficits, such as poor social behavior (onset prior to weaning) and depressive-like behaviors (onset post- weaning (Raineki et al., 2012, Raineki et al., 2010b, Sevelinges et al., 2011, Sullivan et al., 2000a, Sullivan et al., 2000b). In adulthood, early trauma produces enhanced aggression (Marquez et al., 2013) and impaired threat response (Perry, in press).

Fig. 3

Schematic of a visible burrow system for use in rodents and putative effects of early-life abuse on dominance hierarchy formation. This enclosure, adapted from Blanchard et al. (1995), allows for a semi-naturalistic setting in which rodents can be group-housed with limited access to resources including food, water, and receptive females. Social position can emerge from individual differences in aggression and stress reactivity. These factors may be compromised in cases of caregiver abuse in early life, which produces enhanced aggression (Marquez et al., 2013), impaired threat response (Perry, in press), depressive and anxiety-like behavior (Raineki et al., 2012, Raineki et al., 2015 and decreased social exploration (Raineki et al., 2015). As a result, abuse may affect formation and maintenance of a stable dominance hierarchy.