Effects of Early-Life Abuse Differ across Development: Infant Social Behavior Deficits Are Followed by Adolescent Depressive-Like Behaviors Mediated by the Amygdala

Abstract

Abuse during early life, especially from the caregiver, increases vulnerability to develop later life psychopathologies such as depression. Although signs of depression are typically not expressed until later life, signs of dysfunctional social behavior have been found earlier. How infant abuse alters the trajectory of brain development to produce pathways to pathology is not completely understood. Here we address this question using two different but complementary rat models of early-life abuse from postnatal days (PN) 8–12: a naturalistic paradigm, where the mother is provided with insufficient bedding for nest building and a more controlled paradigm, where infants undergo olfactory classical conditioning. Amygdala neural assessment (c-Fos), as well as social behavior and forced swim tests were performed at preweaning (PN20) and adolescence (PN45). Our results show that both models of early life abuse induce deficits in social behavior, even during the preweaning period; however, depressive-like behaviors were observed only during adolescence. Adolescent depressive-like behavior corresponds with an increase in amygdala neural activity in response to forced swim test. A causal relationship between the amygdala and depressive-like behavior was suggested through amygdala temporary deactivation (muscimol infusions), which rescued the depressive-like behavior in the forced swim test. Our results indicate that social behavior deficits in infancy could serve as an early marker for later psychopathology. Moreover, the implication of the amygdala in the ontogeny of depressive-like behaviors in infant abused animals is an important step toward understanding the underlying mechanisms of later life mental disease associated with early-life abuse.

Enduring good memories of infant trauma: Rescue of adult neurobehavioral deficits via amygdala serotonin and corticosterone interaction

“…These findings replicate previous results of early-life FLX treatment (48,53) and are comparable with those obtained after infant trauma, as modeled by paired odor-shock conditioning (Fig. 3C) (12) or rearing with an abusive mother (13,19). Although there was some variation within normal maternal behavior, the maternal behavior of dams with SAL/FLX-treated pups (i.e., half litter SAL; half litter FLX) did not differ from that of dams with undisturbed pups or dams with odor-shock pups (Fig.…”

“…The adult depressive-like phenotype was used as a behavioral assay with and without the infant trauma odor, to assess the safety-signal value of this odor. Our neural measurements focused on the amygdala because it is a critical brain area for both depression (13,49,50) and safety signals (31,34,35,37) (see Fig. 1 for a schematic diagram of the experiments).…”

“…Thus, sensitive period odor-shock conditioning does not elevate CORT levels (27, 28). However, this paradigm produces later-life depressive-like behavior that is causally linked to amygdala dysfunction (12)(13)(14)19). Although shock is painful to pups (12, 24), unpaired presentations of odor and shock do not result in learning or the adult depressive-like phenotype (12, 29), indicating that these effects are specific to infant paired odor shock.…”

“…Long-lasting effects of infant trauma relevant to depression include disruptions in social behavior, alterations in the serotonin (5-HT) system, and amygdala dysfunction (2,(5)(6)(7)(8), which have been replicated by animal models (9)(10)(11)(12)(13)(14)(15). Paradoxically, trauma-linked cues-even those associated with abusive attachment-can elicit strong attraction and feelings of comfort in humans (16,17).…”

Intergenerational transmission of emotional trauma through amygdala-dependent mother-to-infant transfer of specific fear

“…Research shows that brief FC in infancy is usually short-lived, a phenomenon known as infantile amnesia or infantile forgetting, although repeated sessions induce robust retention (26). In contrast, our data demonstrate that one session of maternally transmitted fear learning at PND 13 lasts through early adolescence, indicating retention for at least 30 d (Fig.…”