December 18, 2018
Written by: Barbara Terzic
We’ve heard all about how pregnancy can permanently alter a woman’s brain, but how does mom’s brain (and emotional state) affect baby’s future mental health? Doctors and scientists have consistently seen that prenatal stress has the potential to alter several facets of a baby’s well-being including physical growth, obesity risk, stress levels, and even brain connectivity1! In fact, children born to women who are in the top 15% of the population for depression or anxiety symptoms have double the risk for also developing emotional or behavioral problems, and children born to women who directly experienced the World Trade Center collapse during the attacks on September 11, 2001 while in their third trimester of pregnancy exhibit a higher vulnerability to posttraumatic stress disorder (PTSD)2. However, scientists are still struggling to parse out the exact biological culprits affected by stress that result in downstream health and behavioral issues in babies. This is mainly because the stress different mothers experience is not the same, making it difficult for researchers to model.
However, there are some events that cause stress in nearly everyone in a community: natural disasters. These devastating events, such as hurricanes, floods, or blizzards, provide excellent opportunities for researchers to examine the effects of prenatal stress on childhood neurological outcomes because the stress experience occurs independent of many confounds such as genetic/medical risk factors, socio-economic status, household environment, and maternal characteristics that would normally make interpreting the effects of stress difficult3. Furthermore, since the dates of the events are clearly known scientists can identify the timing of stress exposure during pregnancy, and determine time windows of susceptibility. Before we dive into what natural disasters have taught scientists about the effects of maternal mood on their offspring, we need to understand how a baby’s brain can be modified during pregnancy.
Shaping the Brain
The specific repertoire of gene expression in different cells of our brain is critical for shaping brain circuitry during and after development – and this includes the time we’re in the womb! The term epigenetics describes the modifications placed on top of our DNA material (like earmarks) that control which genes are expressed, when they are expressed, and to what magnitude. Importantly, these different modifications to our DNA are known to be influenced by our environment, allowing our bodies to alter the expression of our genes without altering the core DNA blueprint itself, and providing us with the ability to adapt to external cues. Although epigenetics is extremely important for all cell types in the body (such as directing a liver cell to become a liver cell and not a skin cell), it is especially important in the cells that make up our brain because these cells never regenerate4. Our brain cells, or neurons, must learn to adapt and change in response to our environment as we develop, learn new tasks, and store memories. But how does this concept of epigenetics take us back to human behavior and the brain?
The earliest studies looking into examples of epigenetics’ influence on behavior stemmed from work at McGill University in Montréal around 2004 focusing on maternal nurturing early in life and offspring stress sensitivity. Researchers showed that the amount and type of nurturing a mother rat provided to its pups determined how well that pup responded to stress later in life5. Since then, additional animal and human studies have found correlations between poor care during infancy and long-lasting epigenetic changes in the brain resulting in maladaptive behaviors. Environmental influences on specific epigenetic marks have also been linked to increased risk to addiction, certain eating disorders, learning/memory performance, and mental illnesses such as bipolar, major depressive disorder, psychopathy, and schizophrenia6. These seminal studies seem to suggest that environmental stressors during infancy have the potential to alter epigenetic marks in babies’ brains well into adulthood, but does this also occur when the stressor occurs prenatally? As mentioned earlier, prenatal stress studies in large human populations have been difficult to conduct (understandably so). Cue: natural disasters.
The Trailblazer: Project Ice Storm
In January of 1998, a massive storm swept across the southern Quebec corridor, striking the city with freezing rain and temperatures, killing 35 people, and causing massive damage to trees and electrical infrastructure all over the area. Aside from resulting in damages upwards of $6 billion and being deemed one of the worst natural disasters in Canadian history, the ice storm also eliminated power (and heating) for nearly 3.5 million people for as long as 40 days….during the coldest month of the year. Stress levels were extremely high in certain regions of the city. What was to be done? Naturally, scientists saw this as the perfect experimental opportunity!
Researchers at McGill University quickly recruited over 170 pregnant women during the time of the storm and began tracking the effects of in utero exposure to varying levels of prenatal maternal stress. Dubbed Project Ice Storm, the study was unique in that it was able to separate “objective” stressors (days without power) from “subjective” reactions (stress/psychiatric symptoms) and “physiological” reactions (cortisol levels) in these pregnant women. With this ‘mom data’ on hand, researchers then began the long journey of child follow-ups beginning at 6 months all the way until 19 years of age. Similar to what had been reported in previous animal studies, Project Ice Storm was able to observe significant effects of prenatal maternal stress to later cognitive and linguistic functioning by 5 years of age. In fact, children exposed to high levels of in utero stress had a tendency for lower IQs, impaired language abilities, motor abnormalities, and temperament issues when compared to children exposed to low or moderate levels of stress. Importantly, the researchers were able to link these findings to genome-wide alterations in DNA methylation (a specific type of epigenetic modification) in these affected children7. The early findings of Project Ice Storm, the full analysis of which is still underway, were instrumental in adding to our understanding of how epigenetics and environmental exposures can affect the developing brain in humans and ultimately shape several aspects of our cognition and temperament.
Since Project Ice Storm several additional studies have received funding in order to study the neurobiological and clinical effects of hurricane landfall in young children in the United States. Funded by the National Institutes of Health, the Adolescent Brain Cognitive Development Study (ABCD) is the largest long-term study of brain development in the United States and is working to compare brain function in children born after Hurricane Irma, which ravaged the coast of Florida back in mid-2017. Furthermore, when the U.S. Midwest experienced severe flooding in the summer of 2008, researchers rushed to collect data on pregnant women exposed to stress and are still observing developmental milestones in their children. Although the neurological assessments are still underway, the children of these Iowa women have already demonstrated changes in language and cognitive functioning7.
Although the findings of these and other human studies were illuminating, it is difficult to control for the varying genetics (i.e., DNA) between different people that may be underlying or contributing to stress susceptibility or other behaviors; we need to continue to observe more people in different countries, with different genetic backgrounds, and different cultures to more thoroughly understand stress effects on childhood cognitive function and mood disturbances. However, over the last several decades the preliminary work in this field has demonstrated a profound role for maternal stress during pregnancy in shaping the health of their children even well beyond infancy.
1VanTieghem MR & Tottenham N. Neurobiological programming of early life stress: Functional development of amygdala-prefrontal circuitry and vulnerability for stress-related psychopathology. Current Topics in Behavioral Neurosciences. 2017
2Yehuda R, Engel SM, Brand SR, Seckl J, Marcus SM, Berkowitz GS. Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy. The Journal of Clinical Endocrinology & Metabolism, 2005; 90(7), 4115-4118.
3Dancause KN, Laplante DP, Hart KJ, O’Hara MW, Elgbeili G, Brunet A, and King S. Prenatal stress due to a natural disaster predicts adiposity in childhood: The Iowa Flood Study. Journal of Obesity. 2015; 2015, 1-10.
3Moore DS. The developing genome: an introduction to behavioral epigenetics. 2015; (1st ed.), Oxford University Press.
4Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ. Epigenetic programming by maternal behavior. Nature Neuroscience. 2004; 7(8), 847-854.
5Cao-Lei L, de Rooij SR, King S, Matthews SG, Metz GAS, Roseboom TJ, Szyf M. Prenatal stress and epigenetics. Neuroscience and Biobehavioral Reviews. 2018; 5(1), 81-93.
6Laplante DP, Brunet A, Schmitz N, Ciampi A, King S. Project Ice Storm: prenatal maternal stress affects cognitive and linguistic functioning in 5 ½-year-old children. J Am Acad Child Adolesc Psychiatry. 2008; 47(9), 1063-72.
7Laplante DP, Kart KJ, O’Hara, MW, Brunet A, and King S. Prenatal maternal stress is associated with toddler cognitive functioning: The Iowa Flood Study. Early Human Development. 2018; 116, 84-92.
Cover image from taxaus1 via Flickr, CC BY 2.0. https://flic.kr/p/E3Pu4U