The impact of early life adversity on brain development

There's no denying that early life influences can shape a child's development. Research suggests that children who experience early life adversity such as prenatal maternal depression, childhood poverty and maltreatment may cope better in high-stress environments in the short-term, but have poorer cognitive and mental health outcomes in later life.

By Chan Shi Yu

Brain Development

Early life adversity

Early experiences can have lasting effects on future outcomes, making exposure to early life adversity an area of great research interest. Measures for early life adverse events range from prenatal maternal stress and depression to postnatal environmental factors such as the extent and quality of parental care, childhood poverty and maltreatment. Early life adversity may lead to future emotional and cognitive problems, affecting school performance, and has been linked to increased prevalence of mental health issues¹.

A population survey in the United States suggests that childhood adversities are linked to around 30 percent of later-onset mental disorders². But what are the pathways that lead from early life experiences to future mental health outcomes? Neuroimaging studies suggest that altered brain development and maturation could be involved.

What information can neuroimaging techniques tell us?

Structural and functional neuroimaging data can be collected without exposure to ionising radiation with magnetic resonance imaging (MRI). Several types of information can be obtained that reveal insights on how the brain is organised. Functional connectivity looks at synchronous activity of different brain regions over time. Several regions have been shown to consistently activate together, and in response to a particular stimulus, and are presumed to be involved in the same function, forming the basis of functional brain networks. Structural connectivity looks at the tracts linking different brain regions, and can be thought of as brain infrastructure supporting communication. As the brain matures, connectivity between different brain regions changes as a result of gene-environment interaction. In most cases, brain connectivity becomes more specialised and localised. Finally, we can also measure morphometric information about the brain, including the thickness and volume of specific brain regions.

Brain diagram

Early life adversity effects on brain development

Numerous studies have suggested that brain development and maturation is accelerated in children who experience early life adversity. Brain structural measures and functional organisation in children exposed to early life adversities are more adult-like than what is observed in typically developing children. For example, one of the key brain regions involved in emotional processing is the amygdala. Functional connectivity patterns between the amygdala and the prefrontal cortex in children exposed to early life adversities match those observed in adults, but are different in typically developing children³. Larger amygdala volumes and enhanced amygdala activation were also observed in children with mothers who experienced depression, and in children who experienced caregiver adversity respectively compared to typically developing children^4,5.

This finding has been replicated in the GUSTO cohort where lower maternal sensitivity and lower response to children’s needs were linked to larger amygdala volumes⁶. However, other studies have suggested that these brain changes are not observed uniformly across the brain, and that changes are localised to different functional networks. Smaller volumes were observed after early life adversity for the hippocampus and prefrontal cortex, two regions strongly linked to cognition^7,8. This localisation of brain changes is reflected in behavioural outcomes. Studies have suggested a diverging trajectory for emotional regulation and cognition, where children who experience early life adversity are better at emotional learning but perform worse at cognitive outcomes.

Taken together, this suggests that accelerated development is a result of the brain adapting to manage early adverse events. For example, a greater capacity for emotional learning could be helpful in dealing with high stress environments. However, this prioritisation may have lasting consequences leading to less favourable cognitive and mental health outcomes. For one, enhanced emotional processing could lead to increased emotional response and threat detection in later life, as well as increased vulnerability to stress-related disorders⁹. This is supported by studies in mice showing that mice exposed to early adversity have enhanced responsiveness to stress¹⁰. Secondly, accelerated brain development is thought to represent premature termination of brain plasticity¹¹. Plasticity is the brain’s ability to learn and adapt to a changing environment and different experiences, and early life has several critical developmental periods. Brain plasticity is also of particular interest because abnormal plasticity during developmental has been linked to disorders like autism and psychosis^12,13.

In summary, experiences in early childhood are important for brain development, and growing up in a high stress environment could result in short-term benefits to emotional learning, but have lasting negative consequences on mental health outcomes.

Brain connectivity as an intervention target

While it may seem discouraging that the seeds for future issues are planted so young, the ability of the brain to learn and adapt also presents an opportunity to improve outcomes. It is not inconceivable that interventions targeting brain connectivity or stress responses could help improve future outcomes. Cognitive training has been shown to alter brain connectivity and improve performance in cognitive tasks. However, to identify the most effective targets, we need a better understanding of the relationship between early life adversity, brain connectivity and future outcomes. The longitudinal studies going on in GUSTO, S-PRESTO and MAMS seek to further answer important research questions (for example, effect of gender, uniform across the whole brain or are specific functional networks particularly vulnerable, characteristics that promote resilience); and test potential targets to modulate that can lead to improvements in outcome.

References

Nelson CA, Scott RD, Bhutta ZA, Harris NB, Danese A, Samara M. Adversity in childhood is linked to mental and physical health throughout life. BMJ. 2020 Oct 28;371:m3048.
Green JG, McLaughlin KA, Berglund PA, Gruber MJ, Sampson NA, Zaslavsky AM, et al. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry. 2010 Feb;67(2):113–23.3.
Gee DG, Gabard-Durnam LJ, Flannery J, Goff B, Humphreys KL, Telzer EH, et al. Early developmental emergence of human amygdala-prefrontal connectivity after maternal deprivation. Proc Natl Acad Sci USA. 2013 Sep 24;110(39):15638–43.4.
Lupien SJ, Parent S, Evans AC, Tremblay RE, Zelazo PD, Corbo V, et al. Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth. Proc Natl Acad Sci USA. 2011 Aug 23;108(34):14324–9.5.
Tottenham N, Hare TA, Millner A, Gilhooly T, Zevin JD, Casey BJ. Elevated amygdala response to faces following early deprivation. Dev Sci. 2011 Mar;14(2):190–204.6.
Lee A, Poh JS, Wen DJ, Tan HM, Chong Y-S, Tan KH, et al. Maternal care in infancy and the course of limbic development. Dev Cogn Neurosci. 2019 Dec;40:100714.7.
van Harmelen A-L, van Tol M-J, van der Wee NJA, Veltman DJ, Aleman A, Spinhoven P, et al. Reduced medial prefrontal cortex volume in adults reporting childhood emotional maltreatment. Biol Psychiatry. 2010 Nov 1;68(9):832–8.8.
Teicher MH, Anderson CM, Polcari A. Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum. Proc Natl Acad Sci USA. 2012 Feb 28;109(9):E563-72.9.
Krugers HJ, Arp JM, Xiong H, Kanatsou S, Lesuis SL, Korosi A, et al. Early life adversity: Lasting consequences for emotional learning. Neurobiol Stress. 2017 Feb;6:14–21.10.
Champagne DL, Bagot RC, van Hasselt F, Ramakers G, Meaney MJ, de Kloet ER, et al. Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. J Neurosci. 2008 Jun 4;28(23):6037–45.11.
Callaghan BL, Tottenham N. The Stress Acceleration Hypothesis: effects of early-life adversity on emotion circuits and behavior. Curr Opin Behav Sci. 2016 Feb;7:76–81.12.
Bourgeron T. From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nat Rev Neurosci. 2015 Sep;16(9):551–63.
Forsyth JK, Lewis DA. Mapping the Consequences of Impaired Synaptic Plasticity in Schizophrenia through Development: An Integrative Model for Diverse Clinical Features. Trends Cogn Sci (Regul Ed). 2017 Oct;21(10):760–78.

ABOUT DR CHAN SHI YU

Dr Chan Shi Yu’s research interests lie in studying the pathways that lead to diverse mental health outcomes. In particular, she employs neuroimaging techniques (resting state functional connectivity and morphometric measures) to study how brain organisation and connectivity affects clinical and functional outcomes in psychiatry.

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