Early life stress can leave lasting impacts on the brain

For children, stress can go a long way. A little bit provides a platform for learning, adapting and coping. But a lot of it — chronic, toxic stress like poverty, neglect and physical abuse — can have lasting negative impacts.

A team of University of Wisconsin-Madison researchers recently showed these kinds of stressors, experienced in early life, might be changing the parts of developing children’s brains responsible for learning, memory and the processing of stress and emotion. These changes may be tied to negative impacts on behavior, health, employment and even the choice of romantic partners later in life.

The study, published in the journal Biological Psychiatry, could be important for public policy leaders, economists and epidemiologists, among others, says study lead author and recent UW Ph.D. graduate Jamie Hanson.

"We haven’t really understood why things that happen when you’re 2, 3, 4 years old stay with you and have a lasting impact," says Seth Pollak, co-leader of the study and UW-Madison professor of psychology.

Yet, early life stress has been tied before to depression, anxiety, heart disease, cancer, and a lack of educational and employment success, says Pollak, who is also director of the UW Waisman Center’s Child Emotion Research Laboratory.

"Given how costly these early stressful experiences are for society … unless we understand what part of the brain is affected, we won’t be able to tailor something to do about it," he says.

For the study, the team recruited 128 children around age 12 who had experienced either physical abuse, neglect early in life or came from low socioeconomic status households.

Researchers conducted extensive interviews with the children and their caregivers, documenting behavioral problems and their cumulative life stress. They also took images of the children’s brains, focusing on the hippocampus and amygdala, which are involved in emotion and stress processing. They were compared to similar children from middle-class households who had not been maltreated.

Hanson and the team outlined by hand each child’s hippocampus and amygdala and calculated their volumes. Both structures are very small, especially in children (the word amygdala is Greek for almond, reflecting its size and shape in adults), and Hanson and Pollak say the automated software measurements from other studies may be prone to error.

Indeed, their hand measurements found that children who experienced any of the three types of early life stress had smaller amygdalas than children who had not. Children from low socioeconomic status households and children who had been physically abused also had smaller hippocampal volumes. Putting the same images through automated software showed no effects.

Behavioral problems and increased cumulative life stress were also linked to smaller hippocampus and amygdala volumes.

Why early life stress may lead to smaller brain structures is unknown, says Hanson, now a postdoctoral researcher at Duke University’s Laboratory for NeuroGenetics, but a smaller hippocampus is a demonstrated risk factor for negative outcomes. The amygdala is much less understood and future work will focus on the significance of these volume changes.

"For me, it’s an important reminder that as a society we need to attend to the types of experiences children are having," Pollak says. "We are shaping the people these individuals will become."

But the findings, Hanson and Pollak say, are just markers for neurobiological change; a display of the robustness of the human brain, the flexibility of human biology. They aren’t a crystal ball to be used to see the future.

"Just because it’s in the brain doesn’t mean it’s destiny," says Hanson.

Hormones affect voting behavior

Researchers from the University of Nebraska at Omaha (UNO), the University of Nebraska-Lincoln (UNL) and Rice University have released a study that shows hormone levels can affect voter turnout.

As witnessed by recent voter turnout in primary elections, participation in U.S. national elections is low, relative to other western democracies. In fact, voter turnout in biennial national elections ranges includes only 40 to 60 percent of eligible voters.

The study, published June 22 in Physiology and Behavior, reports that while participation in electoral politics is affected by a host of social and demographic variables, there are also biological factors that may play a role, as well. Specifically, the paper points to low levels of the stress hormone cortisol as a strong predictor of actual voting behavior, determined via voting records maintained by the Secretary of State.

"Politics and political participation is an inherently stressful activity," explained the paper’s lead author, Jeff French, Varner Professor of Psychology and Biology and director of UNO’s neuroscience program. "It would logically follow that those individuals with low thresholds for stress might avoid engaging in that activity and our study confirmed that hypothesis."

Additional authors on the paper are Adam Guck and Andrew K. Birnie from UNO’s Department of Psychology; Kevin B. Smith and John R. Hibbing from UNL’s Department of Political Science; and John R. Alford from the Department of Political Science at Rice University.

The study is part of a larger body of research exploring connections between biology and political orientation, led by Smith and Hibbing. Previous studies have involved twins, eye-tracking equipment and skin conductance in their efforts to identify physical and genetic links to political beliefs.

"It’s one more piece of solid evidence that there are biological markers for political attitudes and behavior," said Smith. "It’s long been known that cortisol levels are associated with your willingness to interact socially – that’s something fairly well established in the research literature. The big contribution here is that nobody really looked at politics and voting behaviors before."

"This research shows that cortisol is related to a willingness to participate in politics," he said.

To reach their conclusion, researchers collected the saliva of over 100 participants who identified themselves as highly conservative, highly liberal or disinterested in politics altogether and analyzed the levels of cortisol found.

Cortisol was measured in saliva collected from the participants before and during activities designed to raise and lower stress. These data were then compared against the participants’ earlier responses regarding involvement in political activities (voting and nonvoting) and religious participation.

"Not only did the study show, expectedly, that high-stress activities led to higher levels of cortisol production, but that political participation was significantly correlated with low baseline levels of cortisol," French explained. "Participation in another group-oriented activity, specifically religious participation, was not as strongly associated with cortisol levels. Involvement in nonvoting political activities, such as volunteering for a campaign, financial political contributions, or correspondence with elected officials, was not predicted by levels of stress hormones."

According to the study, the only other factor that was predictive of voting behavior was age; older adults were likely to have voted more often than younger adults. Research from other groups has also pointed to education, income, and race as important predictors of voting behavior.

In explaining why elevated cortisol could be linked with lower rates of participation in elections, French cited previous experiments in which high levels of afternoon cortisol are linked to major depressive disorder, social withdrawal, separation anxiety and enhanced memory for fearful stimuli.

"High afternoon cortisol is reflective of a variety of social, cognitive, and emotional processes, and may also influence a trait as complex as voting behavior," French suggested.

"The key takeaway from this research, I believe, is that while social scientists have spent decades trying to predict voting behavior based on demographic information, there is much to be learned from looking at biological differences as well," he said. "Many factors influence the decision to participate in the most important political activity in our democracy, and our study demonstrates that stress physiology is an important biological factor in this decision. Our experiment helps to more fully explain why some people engage in electoral politics and others do not."

Stress hormone linked to short-term memory loss as we age

A new study at the University of Iowa reports a potential link between stress hormones and short-term memory loss in older adults.

The study, published in the Journal of Neuroscience, reveals that having high levels of cortisol—a natural hormone in our body whose levels surge when we are stressed—can lead to memory lapses as we age.

Short-term increases in cortisol are critical for survival. They promote coping and help us respond to life’s challenges by making us more alert and able to think on our feet. But abnormally high or prolonged spikes in cortisol—like what happens when we are dealing with long-term stress—can lead to negative consequences that numerous bodies of research have shown to include digestion problems, anxiety, weight gain, and high blood pressure.

In this study, the UI researchers linked elevated amounts of cortisol to the gradual loss of synapses in the prefrontal cortex, the region of the brain that houses short-term memory. Synapses are the connections that help us process, store, and recall information. And when we get older, repeated and long-term exposure to cortisol can cause them to shrink and disappear.

“Stress hormones are one mechanism that we believe leads to weathering of the brain,” says Jason Radley, assistant professor in psychology at the UI and corresponding author on the paper. Like a rock on the shoreline, after years and years it will eventually break down and disappear.

While previous studies have shown cortisol to produce similar effects in other regions of the aging brain, this was the first study to examine its impact on the prefrontal cortex.

And although preliminary, the findings raise the possibility that short-memory decline in aging adults may be slowed or prevented by treatments that decrease levels of cortisol in susceptible individuals, says Radley. That could mean treating people who have naturally high levels of cortisol—such as those who are depressed—or those who experience repeated, long-term stress due to traumatic life events like the death of a loved one.

According to Radley and Rachel Anderson, the paper’s lead author and a second year-graduate student in psychology at the UI, short-term memory lapses related to cortisol start around age 65. That’s about the equivalent of 21 month-old rats, which the pair studied to make their discovery.

The UI scientists compared the elderly rats to four-month old rats, which are roughly the same age as a 20 year-old person. The young and elderly groups were then separated further according to whether the rats had naturally high or naturally low levels of corticosterone—the hormone comparable to cortisol in humans.

The researchers subsequently placed the rats in a T-shaped maze that required them to use their short-term memory. In order to receive a treat, they needed to recall which direction they had turned at the top of the T just 30, 60, or 120 seconds ago and then turn the opposite way each time they ran the maze.

Though memory declined across all groups as the time rats waited before running the maze again increased, older rats with high corticosterone levels consistently performed the worst. They chose the correct direction only 58 percent of the time, compared to their older peers with low corticosterone levels who chose it 80 percent of the time.

When researchers took tissue samples from the rats’ prefrontal cortexes and examined them under a microscope, they found the poor performers had smaller and 20 percent fewer synapses than all other groups, indicating memory loss.

In contrast, older rats with low corticosterone levels showed little memory loss and ran the maze nearly as well as the younger rats, who were not affected by any level of corticosterone—low or high.

Still, researchers say it’s important to remember that stress hormones are only one of a host of factors when it comes to mental decline and memory loss as we age.

(Image caption: Researchers at Cold Spring Harbor Laboratory have identified the neurons in the brain that determine if a mouse will learn to cope with stress or become depressed. These neurons, located in a region of the brain known as the medial prefrontal cortex (green, left image), become hyperactive in depressed mice (right panel is close-up of left, yellow indicates activation). The team showed that this enhanced activity in fact causes depression.)

Dealing with stress – to cope or to quit?

We all deal with stress differently. For many of us, stress is a great motivator, spurring a renewed sense of vigor to solve life’s problems. But for others, stress triggers depression. We become overwhelmed, paralyzed by hopelessness and defeat. Up to 20% of us will struggle with depression at some point in life, and researchers are actively working to understand how and why this debilitating mental disease develops.

Today, a team of researchers at Cold Spring Harbor Laboratory (CSHL) led by Associate Professor Bo Li reveals a major insight into the neuronal basis of depression. They have identified the group of neurons in the brain that determines how a mouse responds to stress — whether with resilience or defeat.

For years, scientists have relied on brain imaging to look for neuronal changes during depression. They found that a region of the brain known as the medial prefrontal cortex (mPFC) becomes hyperactive in depressed people. This area of the brain is well known to play a role in the control of emotions and behavior, linking our feelings with our actions. But brain scans aren’t able to determine if increased activity in the mPFC causes depression, or if it is simply a byproduct of other neuronal changes. 

Dr. Li set out to identify the neuronal changes that underlie depression. In work published today in The Journal of Neuroscience,Li and his team, including Minghui Wang, Ph.D. and Zinaida Perova, Ph.D., used a mouse model for depression, known as “learned helplessness.” They combined this with a genetic trick to mark specific neurons that respond to stress. They discovered that neurons in the mPFC become highly excited in mice that are depressed. These same neurons are weakened in mice that aren’t deterred by stress – what scientists call resilient mice.

But the team still couldn’t be sure that enhanced signaling in the mPFC actually caused depression. To test this, they engineered mice to mimic the neuronal conditions they found in depressed mice. “We artificially enhanced the activity of these neurons using a powerful method known as chemical genetics,” says Li. “The results were remarkable: once-strong and resilient mice became helpless, showing all of the classic signs of depression.”

These results help explain how one promising new treatment for depression works and may lead to improvements in the treatment.

Doctors have had some success with deep brain stimulation (DBS), which suppresses the activity of neurons in a very specific portion of the brain. “We hope that our work will make DBS even more targeted and powerful,” says Li, “and we are working to develop additional strategies based upon the activity of the mPFC to treat depression.”

Next, Li is looking forward to exploring how the neurons in the mPFC become hyperactive in helpless mice. “These active neurons are surrounded by inhibitory neurons,” says Li. “Are the inhibitory neurons failing? Or are the active neurons somehow able to bypass their controls? These are some of the many open questions we are pursuing to understand the how depression develops.”

Migraine Attacks Increase Following Stress

Migraine sufferers who experienced reduced stress from one day to the next are at significantly increased risk of migraine onset on the subsequent day, according to a new study conducted by researchers at the Montefiore Headache Center and Albert Einstein College of Medicine at Yeshiva University. Stress has long been believed to be a common headache trigger. In this study, researchers found that relaxation following heightened stress was an even more significant trigger for migraine attacks. Findings may aid in recommending preventive treatments and behavioral interventions. The study was published online today in Neurology®, the medical journal of the American Academy of Neurology.

Migraine is a chronic condition that affects approximately 38 million Americans. To examine headache triggers, investigators at the Montefiore Headache Center and Einstein conducted a three month electronic daily diary study which captured 2,011 diary records and 110 eligible migraine attacks in 17 participants. The study compared levels of stress and reduction in stress as predictors of headache.

“This study demonstrates a striking association between reduction in perceived stress and the occurrence of migraine headaches,” said study lead author Richard Lipton, M.D., director, Montefiore Headache Center, professor and vice chair of neurology and the Edwin S. Lowe Chair in Neurology, Einstein. “Results were strongest during the first six hours where decline in stress was associated with a nearly five-fold increased risk of migraine onset. The hormone cortisol, which rises during times of stress and reduces pain, may contribute to the triggering of headache during periods of relaxation.”

Data were collected using a custom-programmed electronic diary. Each day participants recorded information about migraine attacks, two types of stress ratings and common migraine triggers, such as hours of sleep, certain foods, drinks and alcohol consumed, and menstrual cycle. They also recorded their mood each day, including feeling happy, sad, relaxed, nervous, lively and bored.

“This study highlights the importance of stress management and healthy lifestyle habits for people who live with migraine,” said Dawn Buse, Ph.D., director, Behavioral Medicine, Montefiore Headache Center, associate professor, Clinical Neurology, Einstein, and study co-author. “It is important for people to be aware of rising stress levels and attempt to relax during periods of stress rather than allowing a major build up to occur. This could include exercising or attending a yoga class or may be as simple as taking a walk or focusing on one’s breath for a few minutes.”

Your stress is my stress

Stress is contagious. Observing another person in a stressful situation can be enough to make our own bodies release the stress hormone cortisol. This is the conclusion reached by scientists involved in a large-scale cooperation project between the departments of Tania Singer at the Max Planck Institute for Cognitive and Brain Sciences in Leipzig and Clemens Kirschbaum at the Technische Universität Dresden. Empathic stress arose primarily when the observer and stressed individual were partners in a couple relationship and the stressful situation could be directly observed through a one-way mirror. However, even the observation of stressed strangers via video transmission was enough to put some people on red alert. In our stress-ridden society, empathic stress is a phenomenon that should not be ignored by the health care system.

Stress is a major health threat in today’s society. It causes a range of psychological problems like burnout, depression and anxiety. Even those who lead relatively relaxed lives constantly come into contact with stressed individuals. Whether at work or on television: someone is always experiencing stress, and this stress can affect the general environment in a physiologically quantifiable way through increased concentrations of the stress hormone cortisol.

“The fact that we could actually measure this empathic stress in the form of a significant hormone release was astonishing,” says Veronika Engert, one of the study’s first authors. This is particularly true considering that many studies experience difficulties to induce firsthand stress to begin with. The authors found that empathic stress reactions could be independent of (“vicarious stress”) or proportional to (“stress resonance”) the stress reactions of the actively stressed individuals. “There must be a transmission mechanism via which the target’s state can elicit a similar state in the observer down to the level of a hormonal stress response.“

During the stress test, the test subjects had to struggle with difficult mental arithmetic tasks and interviews, while two supposed behavioural analysts assessed their performance. Only five percent of the directly stressed test subjects managed to remain calm; the others displayed a physiologically significant increase in their cortisol levels.

In total, 26 percent of observers who were not directly exposed to any stress whatsoever also showed a significant increase in cortisol. The effect was particularly strong when observer and stressed individual were partners in a couple relationship (40 percent). However, even when watching a complete stranger, the stress was transmitted to ten percent of the observers. Accordingly, emotional closeness is a facilitator but not a necessary condition for the occurrence of empathic stress.

When the observers watched the events directly through a one-way mirror, 30 percent of them experienced a stress response. However, even presenting the stress test only virtually via video transmission was sufficient to significantly increase the cortisol levels of 24 percent of the observers. “This means that even television programmes depicting the suffering of other people can transmit that stress to viewers,” says Engert. “Stress has enormous contagion potential.”

Stress becomes a problem primarily when it is chronic. “A hormonal stress response has an evolutionary purpose, of course. When you are exposed to danger, you want your body to respond with an increase in cortisol,” explains Engert. “However, permanently elevated cortisol levels are not good. They have a negative impact on the immune system and neurotoxic properties in the long term.” Thus, individuals working as caregivers or the family members of chronically stressed individualshave an increased risk to suffer from the potentially harmful consequences of empathic stress. Anyone who is confronted with the suffering and stress of another person, particularly when sustained, has a higher risk of being affected by it themselves.

The results of the study also debunked a common prejudice: men and women actually experience empathic stress reactions with equal frequency. “In surveys however, women tend to assess themselves as being more empathic compared to  men’s self-assessments. This self-perception does not seem to hold if probed by implicit measures”

Future studies are intended to reveal exactly how the stress is transmitted and what can be done to reduce its potentially negative influence on society.

Fight Memory Loss with a Smile (or Chuckle)

Too much stress can take its toll on the body, mood, and mind. As we age it can contribute to a number of health problems, including high blood pressure, diabetes, and heart disease. Recent research has shown that the stress hormone cortisol damages certain neurons in the brain and can negatively affect memory and learning ability in the elderly. Researchers at Loma Linda University have delved deeper into cortisol’s relationship to memory and whether humor and laughter—a well-known stress reliever—can help lessen the damage that cortisol can cause. Their findings were presented on Sunday, April 27, at the Experimental Biology meeting.

Gurinder Singh Bains et al. showed a 20-minute laugh-inducing funny video to a group of healthy elderly individuals and a group of elderly people with diabetes. The groups where then asked to complete a memory assessment that measured their learning, recall, and sight recognition. Their performance was compared to a control group of elderly people who also completed the memory assessment, but were not shown a funny video. Cortisol concentrations for both groups were also recorded at the beginning and end of the experiment.

The research team found a significant decrease in cortisol concentrations among both groups who watched the video. Video-watchers also showed greater improvement in all areas of the memory assessment when compared to controls, with the diabetic group seeing the most dramatic benefit in cortisol level changes and the healthy elderly seeing the most significant changes in memory test scores.

From the authors: “Our research findings offer potential clinical and rehabilitative benefits that can be applied to wellness programs for the elderly,” Dr. Bains said. “The cognitive components—learning ability and delayed recall—become more challenging as we age and are essential to older adults for an improved quality of life: mind, body, and spirit. Although older adults have age-related memory deficits, complimentary, enjoyable, and beneficial humor therapies need to be implemented for these individuals.”

Study co-author and long-time psychoneuroimmunology humor researcher, Dr. Lee Berk, added, “It’s simple, the less stress you have the better your memory. Humor reduces detrimental stress hormones like cortisol that decrease memory hippocampal neurons, lowers your blood pressure, and increases blood flow and your mood state. The act of laughter—or simply enjoying some humor—increases the release of endorphins and dopamine in the brain, which provides a sense of pleasure and reward. These positive and beneficial neurochemical changes, in turn, make the immune system function better. There are even changes in brain wave activity towards what’s called the “gamma wave band frequency”, which also amp up memory and recall. So, indeed, laughter is turning out to be not only a good medicine, but also a memory enhancer adding to our quality of life.”