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Early separation from parents causes trauma and early-life stress. Recently, news media across Europe revealed the results of an “accidental” experiment with orphaned children in Romania that became a longitudinal study.

In the United Kingdom, researchers at King’s College London revealed that children rescued from Romanian orphanages have total brain volumes (TBV) that measured 8.57% smaller than other adopted children in England who had not experienced similar parental separations. With every additional month of separation, the TBV was reduced by 3.00-cm3 (0.27%). Reduced TBV is associated with neurodegenerative diseases that cause memory loss (i.e. dementia) and mental illnesses (i.e. schizophrenia).

Nuria K. Mackes et al. published the results this month after analyzing the magnetic resonance images (MRIs) of 67 Romanian adoptees. The adoptees had between 3 and 41 mo of deprivation. They determined that the decline in brain growth during development may be associated with severe cognitive deficits. Unfortunately for these children, removal from negative conditions and placement into loving and enriching environments was unable to rescue them from the stress-induced loss of brain volume.

Other studies determined that loss of brain volume can severely impact the function of complex brain structures involved in learning and memory formation. Stress disrupts brain tissue growth and development (neurogenesis) and its ability to change and adapt continuously throughout life (neuronal plasticity).

The Romanian Orphanage System was a “Slaughterhouse”

In the 1960s, families in Romania with less than five children were heavily taxed when former dictator Nicolae Ceausescu executed a plan to stimulate growth and development. Families that could not meet these population demands were forced to send their children to orphanages where they lived neglected for many years. It is estimated that since the 1960s, over 500,000 children were orphaned.

Daniel Rucăreanu, a survivor of a Romanian orphanage described the system as a “slaughterhouse“. Today, he is President of Federeii, an organization that fights for the rights of institutionalized children.

Over 150 Million Children Worldwide are Orphaned

Worldwide, the number of orphaned children is staggering. The United Nations Children’s Emergency Fund (UNICEF) reports that over 150 million children are orphaned. The causes of separation from parents are numerous but the consequences present long-term trauma for these individuals. With research, we may identify therapeutic targets to understand the mechanism of impaired neurogenesis and neuronal plasticity. Additionally, we can also identify critical periods in development for intervention to rescue children from the long-term effects of early-life stress.

What happens to the body during a stress response?

The loss of parental care at an early age induces stress that is linked to chronic elevation of glucocorticoids within the central nervous system (J.D. Brenner, 2012). Stress can be either psychological or physiological. The response activates the hypothalamus-pituitary-adrenal (HPA) axis. This HPA stimulates the release of corticotropin-releasing hormone (CRH) or corticotropin-releasing factor (CRF) from the hypothalamus in neurons within the paraventricular nucleus (PVN). CRF/CRH binds to receptors in the anterior pituitary to stimulate adrenocorticotropic hormone (ACTH) that stimulates the release of cortisol (CORT) from the adrenal glands in humans or corticosterone in rodents. The response triggers negative feedback to suppress the release of CRH and restore balance to circulating hormones–however chronic stress impairs this feedback pathway.

The "Hellhole" Brain: The Effects of Early-Life Stress and Trauma

When stressed, our sympathetic nervous system is immediately activated. Epinephrine and norepinephrine are released. The response is increased breathing, heart rate, and perspiration. The stress hormones released are apart of the glucocorticoid family of peptide hormones and the cascade of events that occurs is the stress response. (Image from Brian M. Sweis, University of Minnesota)

Overexpression of Corticotropin-Releasing Hormone Induces Brain Atrophy

Rodent studies have revealed that chronic elevation of the stress hormone, corticotropin-releasing hormone (CRH) or corticotropin-releasing factor (CRF) significantly reduces the thickness of the following structures in the mouse brain:

  • Sensorimotor cortex and cingulate cortex, 14% and 24%
  • Paraventricular nucleus and amygdala, 11%
  • Dorsal hippocampus volume, 23%

Mice also had severely impaired motor function and gait assessed with a balance beam ( walking bridge). (Goebel et al., 2010)

Chronic Early-Life Stress Impairs the Development of Self-Regulatory Behaviors

Chronic stress during development caused by adversity or neglect can result in negative behaviors in children and adults. The late Dr. Bruce S. McEwen described it in a review in Cerebrum:

“Chaos in the home and inconsistent parenting impair development of self-regulatory behaviors and can lead to substance abuse, earlier onset of sexual activity, bad decision-making, poor mood control, and poor performance in school.”

McEwen B. S. (2011). Effects of stress on the developing brain. Cerebrum : the Dana forum on brain science2011, 14.

Is recovery possible for victims of early-life stress?

It is believed that enriching environments may become advantageous for recovering victims of early-life stress.

Scientists have utilized environmental enrichment in animals exposed to early-life stress and have found that it may have neuroprotective effects in rodents–however, more research is required for patients to determine what type of enrichment, duration, and intervention timepoints are the most beneficial for neuroprotection. (A. C. Kentner, 2015)

What behavioral assays are used to study stress?

Stress is studied with many behavioral assays. Previous research indicates that stress is also related to impaired sensorimotor function. Therefore studies complete a battery of assays for anxiety-like and depressive-like symptoms coupled with motor function analysis of balance and gait.

Unanswered Questions About the Neuroanatomical Changes of Early-Life Stress

  • Randomized studies were unable to determine the specific timepoint where white matter microstructure changes occur in children who are institutionalized. (Bick et al, 2015)
  • Researchers are working to identify therapeutic targets, develop treatments, and identify the specific timepoints of intervention.

What organizations exist to help orphaned and abandoned children worldwide?

  1. Learn more about Federeii and Daniel Rucăreanu for more information on how you can help orphaned children in Romania (Website Language: Romanian).
  2. Learn more about SOS Children’s Villages and how you can help orphaned and abandoned children worldwide (Website Language: English).
  3. If you know of other organizations that assist orphaned and abandoned children, please contact us!

References

  1. Nuria K. Mackes, Dennis Golm, Sagari Sarkar, Robert Kumsta, Michael Rutter, Graeme Fairchild, Mitul A. Mehta, Edmund J. S. Sonuga-Barke. Early childhood deprivation is associated with alterations in adult brain structure despite subsequent environmental enrichment. Proceedings of the National Academy of Sciences Jan 2020, 201911264; DOI: 10.1073/pnas.1911264116.
  2. Bremner J. D. (2006). Stress and brain atrophy. CNS & neurological disorders drug targets5(5), 503–512. doi:10.2174/187152706778559309.
  3. Kim GW, Kim YH, Jeong GW (2017) Whole brain volume changes and its correlation with clinical symptom severity in patients with schizophrenia: A DARTEL-based VBM study. PLOS ONE 12(5): e0177251. https://doi.org/10.1371/journal.pone.0177251.
  4. McEwen B. S. (2011). Effects of stress on the developing brainCerebrum : the Dana forum on brain science2011, 14.
  5. Kreppner, Jana & Rutter, Michael & Beckett, Celia & Castle, Jenny & Colvert, Emma & Groothues, Christine & Hawkins, Amanda & O’Connor, Thomas & Stevens, Suzanne & Sonuga-Barke, Edmund. (2007). Normality and impairment following profound early institutional deprivation: a longitudinal follow-up into early adolescence. Developmental psychology. 43. 931-46. 10.1037/0012-1649.43.4.93.
  6. Sheridan, M., Drury, S., McLaughlin, K., & Almas, A. (2010). Early institutionalization: neurobiological consequences and genetic modifiersNeuropsychology review20(4), 414–429. doi:10.1007/s11065-010-9152-8.
  7. Bos, K., Zeanah, C. H., Fox, N. A., Drury, S. S., McLaughlin, K. A., & Nelson, C. A. (2011). Psychiatric outcomes in young children with a history of institutionalizationHarvard review of psychiatry19(1), 15–24. doi:10.3109/10673229.2011.549773.
  8. Goebel, M., Fleming, S. M., Million, M., Stengel, A., Taché, Y., & Wang, L. (2010). Mice overexpressing corticotropin-releasing factor show brain atrophy and motor dysfunctionsNeuroscience letters473(1), 11–15. doi:10.1016/j.neulet.2010.01.068.
  9. A. Korosi, E.F.G. Naninck, C.A. Oomen, M. Schouten, H. Krugers, C. Fitzsimons, P.J. Lucassen. Early-life stress mediated modulation of adult neurogenesis and behavior. Behavioural Brain Research. Volume 227. Issue 2. 2012. Pages 400-409. ISSN 0166-4328.
  10. Bick J, Zhu T, Stamoulis C, Fox NA, Zeanah C, Nelson CA. Effect of Early Institutionalization and Foster Care on Long-term White Matter Development: A Randomized Clinical Trial . JAMA Pediatr. 2015;169(3):211–219. doi:https://doi.org/10.1001/jamapediatrics.2014.3212
  11. Kentner A. C. (2015). Neuroprotection and recovery from early-life adversity: considerations for environmental enrichment. Neural regeneration research10(10), 1545–1547. doi:10.4103/1673-5374.165315

Author: Mel Sherman

CEO of Centre Scientific