Decreased amygdala volume in adults after premature birth

Abstract

Premature-born infants have impaired amygdala structure, presumably due to increased stress levels of premature birth mediated by the amygdala. However, accounting for lifelong plasticity of amygdala, it is unclear whether such structural changes persist into adulthood. To address this problem, we stated the following questions: first, are whole amygdala volumes reduced in premature-born adults? And second, as adult anxiety traits are often increased after prematurity and linked with amygdala structure, are alterations in amygdala associated with adults’ anxiety traits after premature birth? We addressed these questions by automated amygdala segmentation of MRI volumes in 101 very premature-born adults (< 32 weeks of gestation and/or birth weight below 1500 g) and 108 full-term controls at 26 years of age of a prospectively and longitudinally collected cohort. We found significantly lower whole amygdala volumes in premature-born adults. While premature-born adults had significantly higher T score for avoidant personality reflecting increased social anxiety trait, this trait was not correlated with amygdala volume alterations. Results demonstrate reduced amygdala volumes in premature born adults. Data suggest lasting effects of prematurity on amygdala structure.

Within amygdala: Basolateral parts are selectively impaired in premature-born adults

“…Furthermore, premature birth is associated with an increased risk for social impairments ( Eryigit-Madzwamuse et al, 2015 , Johnson, 2007 , Pesonen et al, 2008 , Wolke et al, 2019 ). Accordingly, we recently found significantly higher scores on an avoidant personality scale in a cohort of premature-born young adults, reflecting increased social anxiety trait ( Schmitz-Koep et al, 2021 ). Still, although the amygdala has been linked with social anxiety in general and although social impairments were associated with altered functional connectivity of the amygdala in preterm-born adolescents ( Davidson, 2002 , Davis and Whalen, 2001 , Johns et al, 2019 ), we did not find evidence that social anxiety was correlated with global amygdala volume alterations ( Schmitz-Koep et al, 2021 ).…”

“…Accordingly, we recently found significantly higher scores on an avoidant personality scale in a cohort of premature-born young adults, reflecting increased social anxiety trait ( Schmitz-Koep et al, 2021 ). Still, although the amygdala has been linked with social anxiety in general and although social impairments were associated with altered functional connectivity of the amygdala in preterm-born adolescents ( Davidson, 2002 , Davis and Whalen, 2001 , Johns et al, 2019 ), we did not find evidence that social anxiety was correlated with global amygdala volume alterations ( Schmitz-Koep et al, 2021 ). However, as mentioned above, the amygdala is not a homogenous structure but consists of several nuclei, which can be assigned to three subdivisions based on their distinct developmental pathways.…”

“…Stress exposure in turn modulates amygdala structure and function, making it vulnerable to prematurity ( Hölzel et al, 2010 , McEwen et al, 2016 , Roozendaal et al, 2009 ). Indeed, reduced whole amygdala volumes have already been described in neonates, children, and adults after premature birth ( Cismaru et al, 2016 , Peterson et al, 2000 , Schmitz-Koep et al, 2021 ), indicating lasting changes in amygdala structure in human prematurity.…”

“…multi-nuclei structures such as thalamus and neuromodulatory nuclei such as basal cholinergic forebrain, with most of these structural changes being linked with adverse neurodevelopmental outcomes ( Ball et al, 2013 , Berndt et al, 2019 , Eikenes et al, 2011 , Grothe et al, 2017 , Hedderich et al, 2019 , Hedderich et al, 2020a , Hedderich et al, 2020b , Menegaux et al, 2020 , Menegaux et al, 2021 , Meng et al, 2016 , Northam et al, 2011 , Nosarti et al, 2002 , Nosarti et al, 2008 , Pascoe et al, 2019 , Rimol et al, 2019 , Schmitz‐Koep et al, 2020 , Skranes et al, 2007 , Skranes et al, 2013 ). One subcortical grey matter structure of particular interest is the amygdala, which is thought to mediate the brain’s stress response to environmental stressors in the context of premature birth ( Chau et al, 2019 , Scheinost et al, 2016 , Schmitz-Koep et al, 2021 ). Prematurely born neonates and infants are exposed to many potential stressors such as maternal separation, extra-uterine conditions under conditions of immaturity, pain, diagnostic procedures, and treatment procedures such as mechanical ventilation and potential surgery, which have been associated with altered brain development ( Anand, 2000 , Duerden et al, 2018 , Grunau, 2013 , Ranger et al, 2013 , Smith et al, 2011 ).…”

“…Following up on previous work ( Schmitz-Koep et al, 2021 ), in the present study we investigated 101 very premature-born adults and 108 full-term controls at 26 years of age using automated FreeSurfer segmentation of amygdala nuclei ( Saygin et al, 2017 ) in structural MRI to address the following questions: First, are there differential effects of prematurity on individual amygdala nuclei structure? As proxy for amygdala nuclei structure, we used both nuclei volume and structural covariance among nuclei.…”