Separation from parents at a young child is a traumatic incident that causes early-life stress. Recently, news sources throughout Europe (BBC, The Guardian, Telegraph, Daily Mail) released snippets of the “accidental” experiment on orphaned children in Romania that became a longitudinal study of early-life stress and parental separation.

In the United Kingdom, a longitudinal study by 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 or deprivations. With every additional month of separation or deprivation, the TBV was reduced by 3.00-cm3 (0.27%).

The study performed by Nuria K. Mackes et al. and published in Proceedings of the National Academy of Sciences (PNAS) analyzed the MRIs of 67 Romanian adoptees (with between 3 and 41 mo of deprivation). The study determined that the decline in brain growth during development may be associated with severe cognitive and developmental 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 brain volume deficit.

Other studies determined that brain atrophy is coupled with impaired neurogenesis and neuronal plasticity within the hippocampus paired with mental health disorders.

Higher levels of traits including autism, attention deficit hyperactivity disorder (ADHD) and a lack of fear of strangers (disinhibited social engagement disorder) have all been documented.

James Gallagher Health and Science Correspondent of BBC World News

Brief History of the Romanian Orphanage System

In the 1960s in Romanian, families with less than five children were heavily taxed when former dictator Nicolae Ceausescu executed a plan to stimulate growth and development in Romania. As a consequence of being unable to meet these demands, families were forced to send their children to orphanages where they lived neglected for many years.

Daniel Rucăreanu, a survivor of a Romanian orphanage and President of Federeii an organization that fights for the rights of institutionalized children described the orphanage life as a “slaughterhouse”. To this day, he fights against the cruelty of conditions of these orphaned children.

Animal and human studies have shown that parental separation is traumatic with severe neurological consequences that delay development both neurologically and cognitively. The proposed mechanism remains elusive but evidence shows that stress-induced brain atrophy can occur in children and adults suffering the consequences of early-life stress.

What is the fate of these adoptees?

Worldwide, the number of orphaned children is staggering. Children are orphaned by war, violence, socioeconomic despair. The causes of separation from parents are numerous and the consequences present long-term trauma for these individuals. With research, we may identify therapeutic targets to understand the mechanism of impaired neurogenesis and neural 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 and the response activates the hypothalamus-pituitary-adrenal (HPA) axis. Stress stimulates the release of corticotropin-releasing hormone (CRH) or corticotropin-releasing factor (CRF) from the hypothalamus in neurons within the paraventricular nucleus (PVN) of the hypothalamus. CRF/CRH binds to receptors located on 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 homeostasis of circulating hormone — however chronic stress impairs this feedback pathway.

When stressed, our sympathetic nervous system is immediately activated. Epinephrine and norepinephrine are released and 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 occur is the stress response.

Autonomic Nervous System Activation Schematic by Backyard Brains.

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 14%
  • cingulate cortex 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 science, 2011, 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. Although aformentioned study (N. K. Mackes et al. 2020) found that an enriching environment was unable to rescue children from the neuroanatomical deficits caused by the trauma of life in the Romanian orphanage.

Scientists have utilized environmental enrichment in animals exposed to early-life stress and have found that enrichment 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 a multitude of behavioral assays. Previous research indicates that stress is also related to impaired sensorimotor function and studies, therefore, complete a battery of assays for anxiety-like and depressive-like symptoms with motor function analysis of balance and gait.

Alternatively from experimental assays that remove animals from a home environment, we have developed a monitored animal home chamber that allows for 24/7 monitoring of animal behavior at all stages of development — from neonate to adult.

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?

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

This article was originally written by Dr. Shermel Sherman for our partner, Centre Scientific and published on February 1, 2020 on Medium. It has been reposted here with permission.

References

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