Stress during pregnancy increases risk of mood disorders for female offspring

Authored by eurekalert.org and submitted by Wagamaga

High maternal levels of the stress hormone cortisol during pregnancy increase anxious and depressive-like behaviors in female offspring at the age of 2, reports a new study in Biological Psychiatry. The effect of elevated maternal cortisol on the negative offspring behavior appeared to result from patterns of stronger communication between brain regions important for sensory and emotion processing. The findings emphasize the importance of prenatal conditions for susceptibility of later mental health problems in offspring.

Interestingly, male offspring of mothers with high cortisol during pregnancy did not demonstrate the stronger brain connectivity, or an association between maternal cortisol and mood symptoms.

"Many mood and anxiety disorders are approximately twice as common in females as in males. This paper highlights one unexpected sex-specific risk factor for mood and anxiety disorders in females," said John Krystal, MD, Editor of Biological Psychiatry. "High maternal levels of cortisol during pregnancy appear to contribute to risk in females, but not males."

"This study measured maternal cortisol during pregnancy in a more comprehensive manner than prior research," said first author Alice Graham, PhD, of Oregon Health & Science University. To estimate the overall cortisol level during pregnancy, senior author Claudia Buss, PhD, of Charité University Medicine Berlin and University of California, Irvine and colleagues measured cortisol levels over multiple days in early-, mid-, and late-pregnancy. Measurements taken from the 70 mothers included in the study reflected typical variation in maternal cortisol levels. The researchers then used brain imaging to examine connectivity in the newborns soon after birth, before the external environment had begun shaping brain development, and measured infant anxious and depressive-like behaviors at 2 years of age.

"Higher maternal cortisol during pregnancy was linked to alterations in the newborns' functional brain connectivity, affecting how different brain regions can communicate with each other," said Dr. Buss. The altered connectivity involved a brain region important for emotion processing, the amygdala. This pattern of brain connectivity predicted anxious and depressive-like symptoms two years later.

The findings reveal a potential pathway through which the prenatal environment may predispose females to developing mood disorders. The study supports the idea that maternal stress may alter brain connectivity in the developing fetus, which would mean that vulnerability for developing a mood disorder is programmed from birth. This could be an early point at which the risk for common psychiatric disorders begins to differ in males and females.

The article is "Maternal Cortisol Concentrations During Pregnancy and Sex Specific Associations with Neonatal Amygdala Connectivity and Emerging Internalizing Behaviors," by Alice M. Graham, Jerod M. Rasmussen, Sonja Entringer, Elizabeth Ben Ward, Marc D. Rudolph, John H. Gilmore, Martin Styner, Pathik D. Wadhwa, Damien A. Fair, and Claudia Buss (https:/ / doi. org/ 10. 1016/ j. biopsych. 2018. 06. 023 ). It appears in Biological Psychiatry, published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at [email protected] or +1 214 648 0880. Journalists wishing to interview the authors may contact Claudia Buss at [email protected] or +49 (0)30 450 529 222 or Alice Graham at [email protected].

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

John H. Krystal, MD, 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.

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 6th out of 142 Psychiatry titles and 9th out of 261 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2017 Impact Factor score for Biological Psychiatry is 11.982. http://www. biologicalpsychiatryjournal. com

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-MacCoy on August 17th, 2018 at 06:37 UTC »

what are the signs of depression in an infant, hit the bottle?

ZeitgeistSuicide on August 17th, 2018 at 05:56 UTC »

This is a very small N study, especially for females. The associations between the amygdala phenotype with moms cortisol levels were significant for the right brain and nonsignificant for the left. However, effect sizes were not reported, so it's unclear how large this association actually was. Most importantly, the biggest covariate in the model was mothers *post*natal depression. And infant sex was not a moderator of these associations, so it seems like the sex has nothing to do with how the brain architecture develops. It's unclear how much variance is explained once the covariate of maternal postnatal depression is taken into account. This covariate was also significantyl associated with internalizing behaviors, more so than infant sex.

Considering we cant measure brain architecture in utero, it's unclear how much of the effect is actually do to the uterine hormonal environment as opposed to things like mother's attachment behavior which can be linked to postnatal depression. Also the scale for their mediation effect sizes isn't clear but the CI looks very big relative to the reported effect sizes (which are not standard Cohen's d), so there appears to be a ton of error informing the strength of the model. Pretty weak low powered study that fails to report the most relevant numbers. Interestingly however, the N for boys was higher and there was no finding for a mediation of cortisol on amygdala architecture as it informs internalization. That's very odd.

Table 3 makes it look like male and female amygdala connections develop in opposite ways. Can someone speak to that?

Wagamaga on August 16th, 2018 at 23:02 UTC »

High maternal levels of the stress hormone cortisol during pregnancy increase anxious and depressive-like behaviors in female offspring at the age of 2, reports a new study in Biological Psychiatry. The effect of elevated maternal cortisol on the negative offspring behavior appeared to result from patterns of stronger communication between brain regions important for sensory and emotion processing. The findings emphasize the importance of prenatal conditions for susceptibility of later mental health problems in offspring.

Interestingly, male offspring of mothers with high cortisol during pregnancy did not demonstrate the stronger brain connectivity, or an association between maternal cortisol and mood symptoms.

"Many mood and anxiety disorders are approximately twice as common in females as in males. This paper highlights one unexpected sex-specific risk factor for mood and anxiety disorders in females," said John Krystal, MD, Editor of Biological Psychiatry. "High maternal levels of cortisol during pregnancy appear to contribute to risk in females, but not males."

https://www.eurekalert.org/pub_releases/2018-08/e-sdp081618.php

Study https://linkinghub.elsevier.com/retrieve/pii/S0006322318316652