Scars of Childhood Stress Visible in the Brain

Batya Swift Yasgur, MA, LSW

June 21, 2018

Stress in early childhood accelerates brain maturation, while stress experienced in adolescence delays it, new research suggests.

Investigators followed 37 individuals from early childhood through adolescence and examined the impact of negative life events and negative social experiences on brain development using MRI scans.

The researchers evaluated these stressors at two life stages: early childhood (0 to 5 years), and adolescence (14 to 17 years). They found that stress in early childhood appeared to be related to faster maturation of the prefrontal cortex and amygdala during adolescence.

In contrast, current adolescent stress was connected to slower maturation of the hippocampus, anterior cingulate, parahippocampus, and prefrontal cortex.

"The crucial difference in these effects concerns when the stress occurred," lead author Anna Tyborowsky, PhD candidate at Radboud University, Nijmegen, the Netherlands, told Medscape Medical News.

"What we see in this study is that not only the type of stress but, more importantly, when it occurred has a differential effect on neural maturation."

The study was published online June 15 in Scientific Reports.

Neurodevelopmental Trajectories

"Adolescence is a critical development stage during which a cascade of biological changes leads to profound structural modifications in the brain," the authors write.

Maturation of adolescents is "protracted," so brain development is
particularly sensitive to neurodevelopmental trajectories "influenced by incubated effects of early-life stressors."

"We know that high levels of chronic stress can be detrimental for our health, but little is known [about] how different types of stressors, encountered during different developmentally sensitive periods, impact neural maturation," Tyborowska commented.

"We know that regions such as the prefrontal cortex and amygdala are highly susceptible to stress, and these are the same regions that are maturing during adolescence and are involved in social-emotional functioning," she explained.

Additionally, longitudinal gray matter volume (GMV) changes in adolescents may raise risk for later-life psychopathology (ie, callous traits and internalizing symptoms).

To investigate the impact of childhood stress on the adolescent brain, the researchers studied 37 children (15 male) who participated in the Nijmegen Longitudinal Study on Child and Infant Development.

Age-relevant measures of the individual's social environment (SE) were used, with the quality of parent-child interactions serving as an index of early SE. Parent-child interactions were assessed when the children were 15 and 28 months old and 5 years old.

Peer environment between age 14 and 17 was assessed in the classroom. Children were asked to nominate classmates they liked and disliked; this information was used to tabulate social preference for each child, since one of the most stressful life events for an adolescent is having poor relationships with peers.

Parental self-report was used to assess both early-childhood negative events and adverse current life events.

When participants were 17 years old, parents completed the Child Behavior Checklist (CBCL) to assess the frequency of emotional and behavioral problems exhibited by the adolescent in the past 6 months.

Adolescents and parents also completed the Inventory of Callous Unemotional Traits.

Neurodevelopmental trajectories were estimated through use of a structural index of brain development (GMV), which measures brain maturation. Brain development was assessed by MRI at ages 14 and 17 years.

"Defining the contribution of these stressors on maturation of neural circuits during adolescence opens the way for us to understand both stress susceptibility and resilience later in adulthood," Tyborowska noted.

Earlier Maturation

Early-life stress profoundly affected changes in brain structure between ages 14 and 17.

Adolescents who had experienced more negative personal events prior to age 5 (eg, illness or divorce) showed larger reductions in GMV in subcortical structures, such as the putamen, insula, caudate, and thalamus, as well as cortical areas spanning the prefrontal, frontal, posterior cingulate, and temporal cortex.

By contrast, GMV changes that were of a similar direction but were of different types occurred in the amygdala — ie, a larger number of negative personal early-life events was associated with a lack of growth in this region between ages 14 and 17.

Regarding current adolescent stress, youngsters who experienced variations in peer environment showed less GMV reduction in the anterior cingulate, parahippocampus, and prefrontal cortex and an increased GMV in the hippocampus.

The researchers used two models to test for the interaction of early and current stressors, as well as the effect of socioeconomic status (SES) on GMV changes.

In the first model, the interaction of negative personal early-life events and the adolescent peer environment did not cause significant changes in GMV.

This showed that "early and current stress are independently related to neurodevelopmental maturation," the authors comment.

In the second model, SES also did not significantly modulate GMV changes.

To assess the behavioral relevance of longitudinal GMV changes observed in the adolescent sample, the researchers explored whether volumetric changes in regions affected by early-life stress were related to the presence of internalizing symptoms and whether adolescent social stress was related to callous-unemotional traits.

After controlling for early-life and current-life events, early social environment, and the participants' sex, a correlational analysis of gray matter volume changes and callous-unemotional traits revealed a positive relationship localized to the right anterior cingulate cortex (r = 0.39; P = .018; Bayes factor = 6.05).

The authors explain that this developmental GMV decrease was associated with the presence of more callous-unemotional traits. The association remained significant, even when controlling for adolescent social environment (r = 0.33; P = .048).

However, the relationship was not found in the bilateral orbitofrontal cortex, and there were no significant associations between internalizing symptoms and developmental GMV changes.

"Increased neural maturation was related to more negative early-life events," said Tyborowska.

She explained that decreased GMV across adolescence is thought to underlie dendritic pruning — a process in which the brain refines its connections — and is therefore a sign of maturation.

"According to the principles of evolutionary biology, growing up in an unsure, stressful environment poses a risk to the organism so that the system is therefore pushed toward earlier maturation to ensure survival of the species, when long-term survival is not certain," she said.

However, the opposite neuromaturational effects seen in adolescence in relation to current stress may delay or potentially disrupt neural maturation.

"More research is needed to understand the interplay between these two effects," she said, adding, "the effect of early-life stress on changes in gray matter development many years later in adolescence is striking."

Migrant Children at High Risk

Commenting on the study for Medscape Medical News, Kate Humphreys, PhD, EdM, postdoctoral fellow, Department of Psychology, Stanford University, California, and adjunct assistant clinical professor, Department of Psychiatry and Behavioral Sciences, Tulane University School of Medicine, New Orleans, Louisiana, who was not involved with the study, said, it has long been known that different brain regions mature at different rates and on different time scales, so "it is not surprising that the impact of stressors will have a differential impact, depending on when the events occur."

She expressed concern that the sample size was "relatively small," so "replication would be necessary to be more confident in these results."

However, she added, the study has important take-home messages.

"Finding ways to reduce stress exposure among young children should be a priority," said Humphreys.

"Given the current administration's practice of separating even very young children from their caregivers, even when seeking asylum in the US, is not only catastrophic for those parents and children emotionally, but the scars of parental separation and other forms of early stress have long-term consequences for these families and everyone with whom they come into contact," she said.

Tyborowska noted that the study did not investigate the "buffering effects of stress or resilience mechanisms."

It may be "especially important to look for interventions that can buffer the effects of stress during these sensitive developmental periods," she said.

This researchers ' work was supported by the European Research Council, the Netherlands Organization for Scientific Research, and a Marie Curie Individual Fellowship within the European Union ' s Horizon 2020 Framework Programme. The authors and Dr Humphreys have disclosed no relevant financial relationships.

Sci Rep. Published online June 15, 2018. Full text

For more Medscape Psychiatry news, join us on Facebook and Twitter.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: