Influence of Severity of Type and Timing of Retrospectively Reported Childhood Maltreatment on Female Amygdala and Hippocampal Volume

Abstract

Deleterious effects of adverse childhood experiences (ACE) on human brain volume are widely reported. First evidence points to differential effects of ACE on brain volume in terms of timing of ACE. Upcoming studies additionally point towards the impact of different types (i.e., neglect and abuse) of ACE in terms of timing. The current study aimed to investigate the correlation between retrospectively reported severity of type (i.e., the extent to which subjects were exposed to abuse and/or neglect, respectively) and timing of ACE on female brain volume in a sample of prolonged traumatized subjects. A female sample with ACE (N = 68) underwent structural magnetic resonance imaging and a structured interview exploring the severity of ACE from age 3 up to 17 using the "Maltreatment and Abuse Chronology of Exposure" (MACE). Random forest regression with conditional interference trees was applied to assess the impact of ACE severity as well as the severity of ACE type, (i.e. to what extent individuals were exposed to neglect and/or abuse) at certain ages on pre-defined regions of interest such as the amygdala, hippocampus, and anterior cingulate (ACC) volume. Analyses revealed differential type and timing-specific effects of ACE on stress sensitive brain structures: Amygdala and hippocampal volume were affected by ACE severity during a period covering preadolescence and early adolescence. Crucially, this effect was driven by the severity of neglect. Adverse childhood experiences (ACE), i.e. sexual or physical abuse or neglect during childhood, are highly prevalent worldwide 1. Particularly prolonged and repeated ACE constitutes a major risk factor for adult psychopathology 2 such as major depression 3 , substance abuse 4 , personality disorders 5 , anxiety disorders, and posttraumatic stress disorder (PTSD) 6. ACE is further linked to deleterious effects on neurocognitive functioning (i.e., working memory and inhibitory control), mirrored in significant functional and structural alterations in stress and

Recognizing the importance of childhood maltreatment as a critical factor in psychiatric diagnoses, treatment, research, prevention, and education

“…Furthermore, there appear to be marked sex-related differences in the association between CM and brain structure, with greater reported differences in corpus callosum [55] and hippocampus [56] in maltreated males than females. There also appear to be specific sensitive periods when exposure to CM is associated with most significant alterations in structure [56,57] and function [58]. For example, amygdala response to threatening visual stimuli was blunted in adults reporting exposure to physical maltreatment between ages 3-6 years but exacerbated in adults reporting exposure to peer emotional bullying at 13-15 years [58].…”

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

“…A portion of these differences could reflect our finding that greater cumulative stress exposure was associated with smaller amygdala volumes. Recently, Herzog et al (2020) tried to compare the impact of different types of ELAs using cutting-edge statistical methods (random forest regression) and found neglect during childhood and adolescence was related to smaller amygdala volumes. However, work using latent class models to identify classes of ELA (e.g., Family Instability; Direct Victimization) did not find any associations between ELA type(s) and amygdala volume (King et al, 2019).…”

Childhood maltreatment, prefrontal-paralimbic gray matter volume, and substance use in young adults and interactions with risk for bipolar disorder

“…This study also did not investigate age of childhood maltreatment onset or duration. Differences in ELS severity, onset, and duration could have contributed to results 57 , and future studies should incorporate these maltreatment factors.…”