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Children with fetal glucocorticoid exposure showed significant cortical thinning, and a thinner cortex also predicted more emotional problems. Image Credit: University of Maryland Department of Psychology

Glucocorticoids may contribute to fetal brain changes

Glucocorticoids have saved the lives of countless babies, but exposure may also have negative consequences. Excessive glucocorticoid levels may effect brain development, contributing to emotional problems later in life.

Neonatologists seem to perform miracles in the fight to support the survival of premature babies. To promote their survival, cortisol-like drugs called glucocorticoids are administered frequently to women in preterm labor to accelerate their babies' lung maturation prior to birth.

Cortisol is a substance naturally released by the body when stressed. But the levels of glucocorticoids administered to promote lung development are higher than that achieved with typical stress, perhaps only mirrored in the body's reaction to extreme stress.

In Biological Psychiatry, Dr. Elysia Davis at the University of Denver and her colleagues report new findings on the effects of synthetic glucocorticoid on human brain development. Their study focused on healthy children who were born full-term, avoiding the confounding effects of premature birth.

The investigators conducted brain imaging sessions in and carefully assessed 54 children, 6-10 years of age. The mothers of the participating children also completed reports on their child's behavior. The researchers then divided the children into two groups: those who were exposed to glucocorticoids prenatally and those who were not.

In this study, children with fetal glucocorticoid exposure showed significant cortical thinning, and a thinner cortex also predicted more emotional problems.

In one particularly affected part of the brain, the rostral anterior cingulate cortex, it was 8-9% thinner among children exposed to glucocorticoids.

Interestingly, other studies have shown that this region of the brain is affected in individuals diagnosed with mood and anxiety disorders.

"Fetal exposure to a frequently administered stress hormone is associated with consequences for child brain development that persist for at least 6 to 10 years. These neurological changes are associated with increased risk for stress and emotional problems," Davis explained of their findings. "Importantly, these findings were observed among healthy children born full term."

Although such a finding does not indicate that glucocorticoids 'caused' these changes, researchers determined the findings can't be explained by any obvious confounding differences between the groups. The two groups did not differ on weight or gestational age at birth, apgar scores, maternal factors, or any other basic demographics. Thus, the findings do suggest that glucocorticoid administration may somehow alter the trajectory of brain development of exposed children.

"This study provides evidence that prenatal exposure to stress hormones shapes the construction of the fetal nervous system with consequences for the developing brain that persist into the preadolescent period.

"It highlights potential links between early cortisol exposure, cortical thinning and mood symptoms in children. It may provide important insights into the development of the brain and the long-term impact of maternal stress."

Dr. John Krystal, University of Denver, and editor of Biological Psychiatry.

Abstract
Background
Glucocorticoids play a critical role in normative regulation of fetal brain development. Exposure to excessive levels may have detrimental consequences and disrupt maturational processes. This may especially be true when synthetic glucocorticoids are administered during the fetal period, as they are to women in preterm labor. This study investigated the consequences for brain development and affective problems of fetal exposure to synthetic glucocorticoids.

Methods
Brain development and affective problems were evaluated in 54 children (56% female), aged 6 to 10, who were full term at birth. Children were recruited into two groups: those with and without fetal exposure to synthetic glucocorticoids. Structural magnetic resonance imaging scans were acquired and cortical thickness was determined. Child affective problems were assessed using the Child Behavior Checklist.

Results
Children in the fetal glucocorticoid exposure group showed significant and bilateral cortical thinning. The largest group differences were in the rostral anterior cingulate cortex (rACC). More than 30% of the rACC was thinner among children with fetal glucocorticoid exposure. Furthermore, children with more affective problems had a thinner left rACC.

Conclusions
Fetal exposure to synthetic glucocorticoids has neurologic consequences that persist for at least 6 to 10 years. Children with fetal glucocorticoid exposure had a thinner cortex primarily in the rACC. Our data indicating that the rACC is associated with affective problems in conjunction with evidence that this region is involved in affective disorders raise the possibility that glucocorticoid-associated neurologic changes increase vulnerability to mental health problems.

The article is "Fetal Glucocorticoid Exposure Is Associated with Preadolescent Brain Development" by Elysia Poggi Davis, Curt A. Sandman, Claudia Buss, Deborah A. Wing, and Kevin Head (doi: 10.1016/j.biopsych.2013.03.009). The article appears in Biological Psychiatry, Volume 74, Issue 9 (November 1, 2013), published by Elsevier.

Notes for editors
Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Elysia Davis at +1 303 871 3790 or Elysia.Davis@du.edu.

The authors' affiliations, and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry
Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 4th out of 135 Psychiatry titles and 13th out of 251 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2012 Impact Factor score for Biological Psychiatry is 9.247.

About Elsevier
Elsevier is a world-leading provider of scientific, technical and medical information products and services. The company works in partnership with the global science and health communities to publish more than 2,000 journals, including The Lancet and Cell, and close to 20,000 book titles, including major reference works from Mosby and Saunders. Elsevier's online solutions include ScienceDirect, Scopus, SciVal, Reaxys, ClinicalKey and Mosby's Suite, which enhance the productivity of science and health professionals, helping research and health care institutions deliver better outcomes more cost-effectively.

A global business headquartered in Amsterdam, Elsevier employs 7,000 people worldwide. The company is part of Reed Elsevier Group PLC, a world leading provider of professional information solutions. The group employs more than 30,000 people, including more than 15,000 in North America. Reed Elsevier Group PLC is owned equally by two parent companies, Reed Elsevier PLC and Reed Elsevier NV. Their shares are traded on the London, Amsterdam and New York Stock Exchanges using the following ticker symbols: London: REL; Amsterdam: REN; New York: RUK and ENL.

Original press release: http://news.harvard.edu/gazette/story/2007/08/human-stem-cells-help-monkeys-recover-from-parkinsons/