Summary: A new study reports maternal stress during pregnancy can increase the risk of female offspring developing mood disorders. Researchers reveal higher maternal cortisol levels during pregnancy were linked to alterations in newborns’ functional brain connectivity in emotional processing areas.
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.
Source: Rhiannon Bugno – Elsevier
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Original Research: Open access research for “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 in Biological Psychiatry Published July 7 2018.
Maternal Cortisol Concentrations During Pregnancy and Sex Specific Associations with Neonatal Amygdala Connectivity and Emerging Internalizing Behaviors
Maternal cortisol during pregnancy has the potential to influence rapidly developing fetal brain systems that are commonly altered in neurodevelopmental and psychiatric disorders. Research examining maternal cortisol concentrations across pregnancy and offspring neurodevelopment proximal to birth is needed to advance understanding in this area, and lead to insight into the etiology of these disorders.
Participants were N=70 adult women recruited in early pregnancy, and their infants born after 34-weeks gestation. Maternal cortisol concentrations were assessed serially over four days in early, mid, and late gestation. Resting state functional connectivity MRI of the neonatal amygdala was examined. Mothers reported on children’s internalizing behavior problems at 24-months-of-age.
Maternal cortisol concentrations during pregnancy were significantly associated with neonatal amygdala connectivity in a sex specific manner. Elevated maternal cortisol was associated with stronger amygdala connectivity to brain regions involved in sensory processing and integration, as well as the default mode network in females, and with weaker connectivity to these brain regions in males. Elevated maternal cortisol was associated with higher internalizing symptoms in females only, and this association was mediated by stronger neonatal amygdala connectivity.
Normative variation in maternal cortisol during pregnancy is associated with the coordinated functioning of the amygdala soon after birth in a sex specific manner. The identified pathway from maternal cortisol to higher internalizing symptoms in females via alterations in neonatal amygdala connectivity may be relevant for the etiology of sex differences in internalizing psychiatric disorders, which are more prevalent in females.