Differential effects of childhood neglect and abuse during sensitive exposure periods on male and female hippocampus

Abstract

The hippocampus is a highly stress susceptible structure and hippocampal abnormalities have been reported in a host of psychiatric disorders including major depression and post-traumatic stress disorder (PTSD). The hippocampus appears to be particularly susceptible to early life stress with a graded reduction in volume based on number of types (multiplicity) or severity of maltreatment. We assessed whether the most important predictors of adult hippocampal volume were multiplicity, severity or duration of exposure or timing of maltreatment during developmental sensitive periods. 3T MRIs were collected on 336 unmedicated, right-handed subjects (132M/204F, 18-25 years). Exposure to broad categories of abuse and neglect during each year of childhood were assessed using the Maltreatment and Abuse Chronology of Exposure scale and evaluated using artificial intelligence and predictive analytics. Male hippocampal volume was predicted by neglect, but not abuse, up through 7 years of age. Female hippocampal volume was predicted by abuse, but not neglect, at 10, 11, 15 and 16 years. Exposure at peak age had greater predictive importance than multiplicity, severity or duration. There were also marked gender differences in subfields and portions (head, body or tail) affected by exposure. History and symptoms of major depression, PTSD or anxiety disorders were not predictive of hippocampal volume once maltreatment was accounted for. Neglect appears to foster inadequate hippocampal development in males while abuse appears to produce a stress-related deficit in females. Studies assessing hippocampal volume in psychiatric disorders need to control for the gender-specific effects of abuse and neglect.

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

“…This argumentation is in line with the present investigation, as our sample included adults with experience of prolonged and severe maltreatment. With regard to the hippocampus, a number of studies found reduced hippocampal volume in adult samples 23 , while studies in children or adolescents exposed to neglect have not typically observed changes in hippocampus volume 16 . As observed in the amygdala, it is hypothesized that there may be a silent period between exposure to maltreatment and discernible neurobiological differences, with observable cross sectional differences becoming fully discernible in later life 21 .…”

Subcortical structural variations associated with low socioeconomic status in adolescents

“…Early life social adversity results in abnormalities in BDNF methylation and mRNA expression, including in the hippocampus and amygdala (Miskolczi et al, 2019). Also, there are sex differences in BDNF expression (Bath, Schilit, & Lee, 2013) and sensitive periods, and associated effects on amygdala and hippocampal volume (Pechtel, Lyons-Ruth, Anderson, & Teicher, 2014;Teicher et al, 2018). In their model, Miskolczi et al (2019) argue that sex (along with genetic factors) influence brain developmental curves, that the trajectory of these developmental curves are region-specific and furthermore determine the timing of sensitive periods for each region, and that depending on the timing of the early life adversity, separable brain regions might undergo disturbed development, resulting in aberrant maturation and increased risk of psychopathology.…”

Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways

“…See references for details. [160][161][162] The first study was conducted at McLean Hospital's Developmental Biopsychiatry Research Program (PI: Martin Teicher, MD, PhD) entitled "Sensitive Periods, Brain Development and Depression Study". The group aimed to test the hypothesis that there are discrete sensitive periods when exposure to abuse or loss is maximally associated with risk for developing psychiatric disorders, specifically major depression and that risk for developing depression coincided with exposure to abuse during sensitive periods of hippocampal and prefrontal cortex vulnerability.…”