How a fetus’s developing brain may be shaped by mom’s mental state

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Health, athleticism, intelligence, illness: The traits that make us who we are come from the interplay between the genes we inherit and the environment we’re exposed to. And those environmental effects begin even before we are born. Thanks to long-running studies that track offspring from womb to adulthood, we know that smoking during pregnancy is linked to low birth weight, that drinking alcohol can cause heart defects or joint disorders, that a bad diet raises the odds of a child being an obese as an adult.

But what about a mother’s mental health? Until recently, researchers thought that this had an effect only after birth — that if a mother’s poor emotional well-being led to neglectful or abusive parenting, it increased her child’s risk of psychological disorders such as depression, attention deficit hyperactivity disorder, anxiety or other conditions. But a woman’s mental health is an integral part of her fetus’ environment, explains Catherine Monk, a medical psychologist at Columbia University in New York. And a burgeoning body of evidence shows that a pregnant woman’s psychological health can influence that of her child’s.

knowable magazine logoMonk began working with pregnant patients early in her clinical career, and she has spent more than 20 years researching the effects of maternal stress, depression and anxiety on offspring. She recently coauthored a review in the Annual Review of Clinical Psychology describing the mechanisms by which a mother’s mental state may shape her fetus’ developing brain.

Monk spoke with Knowable about the evidence so far, and why she sees this link between a woman and her child’s mental health as a prime opportunity for preventive care — and not a reason to blame Mom. This conversation has been edited for length and clarity.

How did you first try to study whether a woman’s mental state can affect her fetus?

We gave pregnant women in the lab a color-word matching test. It’s a very standard cognitive challenge — when faced with it, we all get a little bit nervous and show an increase in heart rate and blood pressure. We thought we’d see the fetuses respond with a change in heart rate too, but we didn’t see anything statistically significant for these women when their results were pooled.

We had also gathered information about how anxious these women were, using their responses to a standard questionnaire. When we separated the data by low-anxious versus high-anxious groups, we saw that the fetuses of women who were not very anxious didn’t show a heart rate change at all. But fetuses of women who were more anxious had an increased heart rate in response to the stressful task. So that suggested that these fetuses, although they’re receiving similar sounds and other stimuli from their mothers as the other group, are responding differently.

If a fetus’ heart rate changes more in response to cues from its mom, how does that correlate with a greater risk of anxiety and ADHD?

In a subsequent study, we found that a reactive heart rate in fetuses of mothers with prenatal depression was associated with less connectivity between two regions in the brain known as the amygdala and prefrontal cortex. The amygdala is a part of brain circuits involved in regulating emotion, in detecting and experiencing stress responses. The prefrontal cortex is involved in the control of behavior, speech and reasoning, and can dampen the amygdala’s reactivity to stimuli.

So the idea is that even early on, babies of more depressed mothers have less of a connection in their brain between the amygdala and the prefrontal cortex, which may be an early sign of less cognitive control over emotion. Other labs are showing similar links between mood disturbance in pregnant women and this dampening-down of connections between these two parts of the brain. It’s also something we see in experimental studies with animals.


How does a mom’s mental state of anxiety or depression get communicated to the fetus?

We have some pieces of the puzzle. Hormones are one important mechanism. We know from animal studies that exposure to atypically high levels of the steroid stress hormone cortisol in the uterus is associated with more activity in the offspring’s amygdala after birth. These animals show more anxiety-like behavior.

There’s a lot of data from human studies as well. For example, in one study of women waiting to undergo amniocentesis, researchers found that if you compare the level of cortisol in a woman’s plasma to that in the amniotic fluid — that’s what the fetus is exposed to — there’s less correlation in women who are less anxious. But there’s a high correlation in more anxious women. This suggests that something about maternal anxiety is associated with the placenta functioning differently, which can affect how much cortisol reaches the amniotic fluid. That’s one of the challenges with this research: It may not matter exactly how much cortisol is in the woman’s circulation, but what level the fetus is exposed to via the placenta and amniotic fluid.

Several groups, including ours, have found that there’s an enzyme in the placenta whose role is to deactivate cortisol as it crosses the placenta and this enzyme’s functioning varies based on women’s anxiety levels. In humans, maternal anxiety seems to be associated with a “turning off” of the gene that controls this protective enzyme so that more cortisol reaches the developing fetus. This exposure to atypically high cortisol levels is associated with decreased nerve cell formation and differences in how neurons migrate and form connections, all of which can contribute to increased risk of anxiety or ADHD.

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Other groups have shown that changes in hormonal regulation because of these placental receptors being switched off are associated with alterations in kids’ behavior, such as being more anxious. We’re now starting to connect these dots and see a more coherent story emerge across different labs.

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Are other mechanisms at work too?

Stress can affect regulation of the immune system. That also influences neurological and behavioral development in the fetus. Inflammatory proteins known as cytokines seem to influence how a neuron grows and forms connections, and also which neurons survive and how they develop. The role of the immune system in brain development is really just beginning to be uncovered.

Are there critical windows during fetal development when the brain is more susceptible to these hormone or immune signals?

That’s one of the areas where we still have a way to go. There’s some speculation that if a stress occurs earlier during pregnancy there’s potential for more profound effects, because more foundational aspects of the developing brain are going to be affected. So you might see a greater risk for schizophrenia, for example. When the stressful event occurs later, you might see more subtle effects, so the risk for more subtle conditions such as ADHD or anxiety is increased.

But this is very preliminary. We’re just starting to get a clearer sense of when maternal stress occurs, whether it was a chronic stress such as lifelong poverty or an acute stress such as a famine, and the outcomes of being exposed to it in utero.

Are the effects of maternal stress always harmful?

I think we tend to think of these exposures as bad. In much of our work, we’re showing negative outcomes — if your mother is stressed or anxious, you have a higher risk of ADHD, and that’s a bad outcome.

But there is another way to look at this, which is that your mother is giving you cues. She’s very anxious that it’s a dangerous world out there. In a risky environment, having an amygdala that’s very reactive, a heart rate and stress response that are reactive — these are adaptations that could help survival.

But then, when a 6-year-old child goes to school, they’re told, “You really need to sit down in your chair and focus,” even though the classroom is very loud. That child has had early prenatal shaping to be super-alert in such an environment. It’s a mismatch between the prenatal cues and the demands of the child’s environment, so he or she may become anxious or have symptoms of ADHD.

The placenta, we know, gets rid of waste and is protective. It’s also this amazingly complex organ that communicates to the fetus what the child’s future environment might be like.

Does any of this suggest that the mother may be to blame for a child’s risk of ADHD?

I think it’s really essential not to blame the mother. We have to be very aware that levels of stress and depression are typically two-fold higher amongst women in poverty. We have to recognize the social conditions that contribute to high levels of stress and depression — and, frankly, society has to take responsibility for that and address it through policy changes.

Should this affect how we care for the health of pregnant women?

Absolutely. Pregnancy is a time of tremendous psychological transition, not just biological change. It’s a great time for screening the woman and the whole family, and making the statement that just as physical health matters, mental health matters too. How a woman is doing: That is the fetus’s environment.

Routine screening for depression and anxiety are becoming part of prenatal practice, and we could be doing more of that. At a minimum, we could start taking seriously the idea that we have more than one patient.

There can be — and I think it’s a deep concern — a privileging of the baby over the mother, at times. In high-risk pregnancies especially, the focus is so much on the fetus and what interventions can be done that there’s less of a focus on the woman, who herself is likely having physical problems, not to mention emotional distress as well, in these contexts.

Some pregnant women want to make positive changes in their life, such as exercising more or getting help coping with past emotional trauma, for their baby’s sake. Others might say their mental health matters to them as individuals, not just because they’re carrying a baby. We, as clinicians, should be caring for a woman’s mental health even if she isn’t pregnant. And we should also realize that when we care for her when she is pregnant, we’re caring for her future child as well.

Jyoti Madhusoodanan is a science journalist based in San Jose, California. Follow her on Twitter @smjyoti

Catherine Monk is a medical psychologist at Columbia University in New York

A version of this article was originally published on Knowable’s website asHow maternal mood shapes the developing brainand has been republished here with permission. 

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