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  • Research has revealed an association between common psychiatric conditions and events occurring during fetal development.
  • A new study now suggests that negative stress experienced in the womb may impact an individual’s response to stressful situations well into their 40s.
  • The results also indicate that exposure to prenatal stress affects males and females differently — and that these effects may last a lifetime.

Stress occurs when demands or challenges cause the brain and the rest of the body to react with emotional or physical tension. Stressors can be perceived as positive or negative.

Positive stress may result from situations that a person feels they can cope with, such as daily challenges and responsibilities related to work or school. There is even evidence that rising to the challenge has some health benefits.

However, day-to-day and moderate stressors can be perceived as negative if the person feels that they lack control.

Negative stress may be more likely to occur during life-altering events such as a divorce, a job loss, or the death of a loved one, and receiving extra social support can help ease the impact.

Health events, including serious complications of pregnancy, such as preeclampsia and infections, can result in major stress.

Scientists recognize the effects that stress can have on physical and mental health. If stress is prolonged, toradol 60mg it can affect the immune system, gastrointestinal tract, cardiovascular system, and reproductive system.

The impact of stress on the reproductive system is an area of study gaining momentum in the scientific community. Recent research has shown that maternal stress can affect pregnancy and fetal metabolic functioning and emotional and cognitive development.

A recent article in the International Review of Neurobiology suggests that maternal stress from life events, natural disasters, anxiety, and depression increases the risk of emotional, behavioral, and cognitive problems for the child later in life.

However, scientists have been unsure whether these effects are short-lived or more lasting.

Prenatal stress: Impact throughout life

In a study that spanned more than 4 decades, scientists from Massachusetts General Hospital and Harvard Medical School followed 40 men and 40 women from before birth to mid-life to reveal whether prenatal stress caused differences in stress regulation into adulthood.

Half of the participants had a history of major depression or psychosis that was in remission. The authors report that their sample was enriched by people whose mothers had obstetric complications, such as fevers and preeclampsia associated with high maternal cytokine levels.

The study appears in Proceedings of the National Academy of Sciences.

The team used data retrieved from the New England Family Study, long-term research that investigates medical risk factors that may originate from pregnancy and in-utero exposures.

The team tested the correlation between the participants’ neurological responses and their prenatal exposure to pro-inflammatory cytokines. The researchers did this by showing the participants negative and neutral images designed to induce a stress response while they were undergoing functional MRI scans.

Pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6, are immune system regulators that initiate a fever or inflammation in response to an infection or trauma. They can also activate in response to stress.

“Given that the stress circuitry consists of regions that develop differently in the male and female brain during particular periods of gestation, and they function differently across our lifespans, we hypothesized that dysregulation of this circuitry in prenatal development would have [a] lasting differential impact on the male and female brain in people with these disorders. We were particularly interested in the role of the immune system, in which some abnormalities are shared across these disorders.”

– Dr. Jill M. Goldstein, first study author and founder and executive director of the Innovation Center on Sex Differences in Medicine, at Massachusetts General Hospital

Data reveal sex differences

The results of the MRI scans showed differences, on average, in how prenatal exposure to maternal stress-induced pro-inflammatory cytokines affected males and females 45 years later.

Among all the participants, lower prenatal levels of TNF-alpha were associated with more activity in a brain region called the hypothalamus. This is responsible for coordinating brain activity and the regulation of cortisol, a stress hormone.

However, in males only, lower levels of TNF-alpha caused more active communication between the hypothalamus and the area of the brain responsible for controlling impulses and emotions, the anterior cingulate.

In female participants, higher prenatal exposure to interleukin-6 correlated with increased activity in the hippocampus, a brain region that helps control memory and arousal related to stressful stimuli.

The researchers also found that the ratio of TNF-alpha and interleukin-10, an anti-inflammatory cytokine, affected how the hippocampus and hypothalamus communicated.

This effect on communication was also contingent on whether the participant was male or female.

Potential for prevention and treatment?

According to its authors, the new study demonstrates that high levels of maternal stress may affect the brain development of male and female embryos and fetuses differently — and that these effects then influence the person’s ability to regulate stress, possibly throughout life.

Dr. Goldstein observes, “Given that these psychiatric disorders are developing differently in the male and female brain, we should be thinking about sex-dependent targets for early therapeutic intervention and prevention.”

Limitations of the study

The study provides some data-based correlations between maternal inflammatory conditions and stress responses to images in their offspring 45 years later. However, because the study was small, it may not be appropriate to draw general conclusions from the findings.

Also, while the research builds on existing evidence that stress in the prenatal period is associated with worse outcomes, no research has ever assessed how these participants respond to stress in real-life conditions.

Other research suggests that women experience more stress than men. In the present study, the recorded differences in sex may reflect chronic stress, possibly related to societal pressures and expectations.

As many as 1 in 3 of the mothers who took part in the study had an infectious disease and 1 in 6 had preeclampsia, conditions known to increase cytokine levels.

Because the composition of the study group was skewed toward those with obstetric complications, it may not be useful to apply the study findings to general stress in all pregnant people.

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