Abstract
Early life adversity (ELA), such as child maltreatment or child poverty, engenders problems with emotional and behavioral regulation. In the quest to understand the neurobiological sequelae and mechanisms of risk, the amygdala has been of major focus. While the basic functions of this region make it a strong candidate for understanding the multiple mental health issues common after ELA, extant literature is marked by profound inconsistencies, with reports of larger, smaller, and no differences in regional volumes of this area. We believe integrative models of stress neurodevelopment, grounded in “allostatic load,” will help resolve inconsistencies in the impact of ELA on the amygdala. In this review, we attempt to connect past research studies to new findings with animal models of cellular and neurotransmitter mediators of stress buffering to extreme fear generalization onto testable research and clinical concepts. Drawing on the greater impact of inescapability over unpredictability in animal models, we propose a mechanism by which ELA aggravates an exhaustive cycle of amygdala expansion and subsequent toxic-metabolic damage. We connect this neurobiological sequela to psychosocial mal/adaptation after ELA, bridging to behavioral studies of attachment, emotion processing, and social functioning. Lastly, we conclude this review by proposing a multitude of future directions in preclinical work and studies of humans that suffered ELA.
Highlights
The amygdala has been the focus of a great deal of attention in research aimed at understanding the effects of Early Life Adversity (ELA)
ELA exposure and potential of an allostatic load model to disentangle apparent inconsistencies in these findings. We extend this idea, pulling from parallel models put forth in research studies focused on autism and neurodevelopment, and integrating preclinical rodent and nonhuman primate findings, to make specific hypotheses about human behavioral and clinical correlates of specific cellular and neurotransmitter changes
McEwen’s group showed antidepressant treatment could reverse hippocampal changes and related spatial learning deficits (Conrad et al, 1996), but, more importantly, a sensitization to fear learning was untouched by the treatment. These investigators concluded “the results indicate a powerful effect of repeated restraint stress on another brain region, possibly the amygdala, which overrides any influence of the hippocampus” (Conrad et al, 1999)
Summary
The amygdala has been the focus of a great deal of attention in research aimed at understanding the effects of Early Life Adversity (ELA). In ASD, volumetric overgrowths have been reported early in development, but smaller volumes have been noted later in life (Nacewicz et al, 2006; Schumann and Amaral, 2006; Mosconi et al, 2009; Kim et al, 2010) and the rate or degree of early life overgrowth or later life shrinkage is associated with quantitative social impairments The amygdala may reach a breaking point of over-excitation that leads to smaller structural volumes, while higher functional reactivity and excitatory tone are still present This fits with the smaller volumes typically noted in adult samples exposed to stress, echoing rodent hippocampal models predicting that high ratios of inhibitory neurons are metabolically more costly if unable to reduce high firing rates of excitatory neurons (Wang et al, 2020). Thoughtful execution of these multiple ideas, across preclinical and human studies, could significantly advance our understanding of the neurobiological sequelae of ELA, the mediating connections between ELA and psychopathology, and more basic science questions such as nature vs. nurture
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