Longitudinal changes in amygdala, hippocampus and cortisol development following early caregiving adversity

Abstract

Although decades of research have shown associations between early caregiving adversity, stress physiology and limbic brain volume (e.g., amygdala, hippocampus), the developmental trajectories of these phenotypes are not well characterized. In the current study, we used an accelerated longitudinal design to assess the development of stress physiology, amygdala, and hippocampal volume following early institutional care. Previously Institutionalized (PI; N = 93) and comparison (COMP; N = 161) youth (ages 4–20 years old) completed 1–3 waves of data collection, each spaced approximately 2 years apart, for diurnal cortisol (N = 239) and structural MRI (N = 156). We observed a developmental shift in morning cortisol in the PI group, with blunted levels in childhood and heightened levels in late adolescence. PI history was associated with reduced hippocampal volume and reduced growth rate of the amygdala, resulting in smaller volumes by adolescence. Amygdala and hippocampal volumes were also prospectively associated with future morning cortisol in both groups. These results indicate that adversity-related physiological and neural phenotypes are not stationary during development but instead exhibit dynamic and interdependent changes from early childhood to early adulthood.

Amygdala Allostasis and Early Life Adversity: Considering Excitotoxicity and Inescapability in the Sequelae of Stress

“…Such experiences, perhaps due to subjective perceptions and processes, would then actually be threatening in nature-the lack of a clear attachment figure would cause heightened vigilance to environmental dangers. This actually fits well with results from Tottenham's group that has found postinstitutionalized children who suffered early social neglect have alterations in the amygdala, both structurally and functionally (e.g., Cohen et al, 2013;VanTieghem et al, 2021) and more recently found amygdala volume predicted later stress hormone responses (VanTieghem et al, 2021). Of important note, we believe compelling distinctions exist in non-human animal models of stress for inescapable vs. unpredictable stressors, but believe it still too early to synthesize these ideas to the exposure vs. experience distinction in humans.…”

“…For example, recent longitudinal work (Whittle et al, 2013) suggest a slowing of growth of the amygdala after ELA. Particularly important to highlight, youth who suffered early social neglect, one form of ELA, had a reduced growth rate of the amygdala, resulting in smaller volumes by adolescence (VanTieghem et al, 2021) and it is as-yet unknown if this represents a delay or a missed critical period to learn fear and safety.…”

Age-related change in task-evoked amygdala—prefrontal circuitry: a multiverse approach with an accelerated longitudinal cohort aged 4-22 years

“…For each scan, we calculated fear > baseline, neutral > baseline, and fear > neutral contrasts. We used native-space bilateral amygdala masks generated using Freesurfer (v6.0; Fischl, 2012) by VanTieghem et al (2021).…”

Amygdala and hippocampal subregions mediate outcomes following trauma during typical development: Evidence from high-resolution structural MRI

“…Animal models have demonstrated that concentrations of glucocorticoid and noradrenaline receptors can be found within subnuclei (i.e., basolateral complex) and subfields (e.g., dentate gyrus) of the amygdala and hippocampus ( Johnson et al, 2005 ; McEwen et al, 1975 ), making them particularly vulnerable to stress-related alterations in their morphology and function ( Vouimba et al, 2007 ). In humans, volumetric reductions in the hippocampus and amygdala following traumatic experiences have been reported in pediatric samples from longitudinal and cross-sectional studies ( Phillips et al, 2021 ; Saxbe et al, 2018 ; VanTieghem, 2021 ; Veer et al, 2015 ; Weissman et al, 2020 ). While most studies examining morphological properties of amygdala and hippocampus following trauma have largely focused on samples at elevated risk for or with established psychopathology symptomology (e.g., Logue et al, 2018 ), only a third of individuals with histories of trauma actually develop clinical levels of psychopathology ( MacMillan et al, 2001 ).…”