A couple of things about memory

First:

Children's Memory May Be More Reliable Than Adults' In Court Cases

Researchers Valerie Reyna, human development professor, and Chuck Brainerd, human development and law school professor--both from Cornell University--argue that like the two-headed Roman god Janus, memory is of two minds--that is, memories are captured and recorded separately and differently in two distinct parts of the mind.

They say children depend more heavily on a part of the mind that records, "what actually happened," while adults depend more on another part of the mind that records, "the meaning of what happened." As a result, they say, adults are more susceptible to false memories, which can be extremely problematic in court cases.

The implications of these results for legal testimony is not what I find especially interesting here. In fact, there are reasons why the testimony of children has sometimes been found to be less reliable than that of adults. Namely, in some cases, the techniques used to interview the children (before trial) have been improperly coercive or suggestive of particular interpretations.

What does seem interesting is the hypothesis that in adults memories of the same event tend to be stored in two distinct forms: literal details of "what happened", and interpretive judgments about the "meaning" of an event. But that in children it is primarily the actual details that are stored.

Reyna and Brainerd's Fuzzy Trace Theory hypothesizes that people store two types of experience records or memories: verbatim traces and gist traces.

Verbatim traces are memories of what actually happened. Gist traces are based on a person's understanding of what happened, or what the event meant to him or her. Gist traces stimulate false memories because they store impressions of what an event meant, which can be inconsistent with what actually happened.

The researchers have experimental evidence to support their conclusions. Some of this is noted in earlier accounts, such as this:

Children Less Prone To False Memories, Implications For Eyewitness Testimony, Study Shows

In a study published in the May issue of Psychological Science, Brainerd and Reyna presented a list of words for groups of first, fifth and ninth graders. Many of the words from this "study list" were related to each other (by belonging to certain categories such as animals, furniture, men's names) while others were unrelated "filler" words.

After a short break, the students were presented with a new "test list" composed of study list words, new words belonging to the aforementioned categories (animals, furniture, etc.), and distracter words that were new and entirely unrelated to the categories or the study list. Their task was to identify whether they had previously heard a word or not.

As predicted, if the test list provided a new word with a closely related meaning (a "semantic relation") to a word from the study list, older children were more likely to assert that they had heard it before. Simply put, the older children had more false memories in this case than younger children.

One can speculate about what's going on here. As people mature through childhood, they are constantly learning about the interrelationship of isolated details and events. (For instance, "Dad acts more scary after he's been drinking beer.") In addition, the accumulation of details makes more literal forms of memory cumbersome (and liable to confusion), so people learn to make abstractions and interpretations that summarize details and make storage easier by associating similar details in more general categories. However, this kind of fuzzy storage (or "fuzzy traces" as Brainerd and Reyna call it) can misrepresent the facts. (For instance, "Dad was drunk when he hit me" – which might not actually be true.)

Second, and not directly related to this, there are two quite indepentdent studies that show something about the relationship between memory and experience of stress.

The first item concerns observation of squirrels:

Correct Levels Of Stress Hormones Boost Learning, Squirrel Study Suggests

Tests on the influence that a stress-related hormone has on learning in ground squirrels could have an impact on understanding how it influences human learning, according to a University of Chicago researcher.

Jill Mateo, Assistant Professor in Comparative Human Development, has found that when they perform normal survival tasks, ground squirrels learn more quickly if they have a modest amount of cortisol, a hormone produced in response to stress, than those with either high or low levels of cortisol.

In humans, cortisol production is also related to stress and is known to have an impact on learning, but that impact is not well understood, Mateo said.

This should sound familiar to anyone who's been through even a few moderately difficult college courses. Namely, if the work in a particular course isn't difficult enough to cause at least a little stress, retention of the details may not be very complete. Without some stress, the material just doesn't seem "important" enough, even if it's new to the student, to compel the student's attention to the details and the complexity. But of course, if the material is difficult enough to cause excessive stress, anxiety can get in the way of successfully organizing the material in the student's mind.

The second study looked at the actual neurobiology of learning under conditions of acute stress:

Short-term Stress Can Affect Learning And Memory

Short-term stress lasting as little as a few hours can impair brain-cell communication in areas associated with learning and memory, University of California, Irvine researchers have found.

It has been known that severe stress lasting weeks or months can impair cell communication in the brain's learning and memory region, but this study provides the first evidence that short-term stress has the same effect.

As it turns out, another stress-related hormone besides cortisol is involved, corticotropin releasing hormone (CRH), and the latter is more significant under conditions of acute stress:

In their study, Baram and her UC Irvine colleagues identified a novel process by which stress caused these effects. They found that rather than involving the widely known stress hormone cortisol, which circulates throughout the body, acute stress activated selective molecules called corticotropin releasing hormones, which disrupted the process by which the brain collects and stores memories.

Learning and memory take place at synapses, which are junctions through which brain cells communicate. These synapses reside on specialized branchlike protrusions on neurons called dendritic spines.

In rat and mouse studies, Baram's group saw that the release of CRH in the hippocampus, the brain's primary learning and memory center, led to the rapid disintegration of these dendritic spines, which in turn limited the ability of synapses to collect and store memories.

The researchers discovered that blocking the CRH molecules' interaction with their receptor molecules eliminated stress damage to dendritic spines in the hippocampal cells involved with learning and memory.

The role of cortisol, in learning under conditions of moderate stress, remains somewhat less clear. In addition to the squirrel study, anecdotal experience with so-called "flashbulb memories" supports the idea that some degree of stress can assist the formation of memories. The Wikipedia article states, without references, "Some biologists believe that the hormone cortisol, which is released in response to stressful incidents, cooperate with epinephrine (adrenaline) to cause the formation of flashbulb memories by the brain, functioning to help remembering things to avoid in the future." The squirrel study suggests cortisol actually has some role in memory formation, rather than being just a coincidental byproduct of stress. (See also the article on Emotion and memory.

Tags: memory, stress, cortisol, corticotropin-releasing hormone

When The Going Gets Tough, Maybe You Should Quit

This caught my eye, because of the connection with "stress", as discussed here and here:

When The Going Gets Tough, Maybe You Should Quit

Are there times when it is better to simply give up? Psychologists have been exploring this question, and more specifically a possible link between tenacity and both physical and mental health.

It would seem that persistence would be tonic over the long haul; hanging tough should increase the odds that you’ll succeed, and personal success is closely linked to well-being. But what if the goal is extremely unlikely? When does an admirable trait like perseverance start to look more like beating your head against the wall?

To test this in the laboratory, psychologists Gregory Miller and Carsten Wrosch developed a psychological instrument that can reliably distinguish between people who when faced with a difficult goal either persist or let go of it. In a series of experiments, the psychologists exhaustively studied these two personality types to see how healthy and well adjusted they are.

In their most recent study, published in the September issue of Psychological Science, a journal of the Association for Psychological Science, the psychologists followed teenagers for a full year. Over that time, individuals who did not persist obtaining hard to reach goals had much lower levels of a protein called CRP [C-reactive protein], an indicator of bodily inflammation. Inflammation has recently been linked to several serious diseases, including diabetes and heart disease.

Well, is it really surprising that there are health benefits associated with having a more easy going, "laid back" personality?

There's a very good book that delves into this in great detail – Why Zebras Don't Get Ulcers, by Stanford professor Robert Sapolsky. (Quick summary is here.)

And while we're on the subject, there's this press release that just came out:

Relationship Between Environmental Stress And Cancer Elucidated

One way environmental stress causes cancer is by reducing the activity level of an enzyme that causes cell death, researchers say.

They found that stress-inducing agents, such as oxidative stress, recruit a protein called SENP1 that cuts a regulator called SUMO1 away from the enzyme SIRT1 so its activity level drops, says Dr. Yonghua Yang, postdoctoral fellow in the laboratory of Dr. Kapil Bhalla, director of the MCG Cancer Center.

This fundamental finding about the relationship between stress and cancer opens the door for treatments that increase SENP1 activity, making it easier for cells that are becoming cancerous to die.

In yet another example of how deeply interrelated different biological processes are, it's worth noting that SIRT1 is a HDAC enzyme, whose activity seems to be enhanced by both resveratrol and calorie restriction. By mechanisms that are still somewhat mysterious, this in turn may be beneficial for longevity. If indeed oxidative stress has the effect of decreasing SIRT1 activity and hence promoting cancer, this may help explain at least some of the longevity benefit of SIRT1.

Tags: stress, inflammation, SIRT1, sirtuins, cancer

The role of hostility, anger, and depression in inflammation

Hasn't it "always" been known that anger and hostility raises one's blood pressure? However that may be, a recent study shows that the connection of hypertension with chronic anger and hostility may involve a disturbed immune system and inflammation – in addition to the well-known blood vessel constriction that is a part of the "fight or flight" stress response.

Hostile Men Could Have Greater Risk For Heart Disease

Men who are hostile and prone to frequent intense feelings of anger and depression could be harming their immune systems and putting themselves at risk for coronary heart disease as well as related disorders like type 2 diabetes and high blood pressure, a new study finds.

The results were found in a 10-year study of U. S. veterans of the Vietnam war.

The men had a series of blood levels taken on three occasions between 1992 and 2002. Researchers measured two immune system proteins known as C3 and C4. Both are markers of inflammation, which is the body’s response to injury or infection. Changes in C3 and C4 are associated with a number of diseases, including some that negatively can affect the arteries around the heart, such as diabetes.

Men whose psychological screening showed the highest level of hostility, depressive symptoms and anger had a 7.1 percent increase in their C3 levels, while men with low levels of these attributes showed no change over the 10-year study period.

Here's another report on this research: Hostility, anger linked to chronic inflammation

But a 2004 study had already demonstrated a stronger correlation between psychological variables and a marker of inflammation (C-reactive protein):

Anger, Hostility And Depressive Symptoms Linked To High C-reactive Protein Levels

Researchers at Duke University Medical Center have discovered that otherwise healthy people who are prone to anger, hostility and mild to moderate depressive symptoms produce higher levels of a substance that promotes cardiovascular disease and stroke.

The substance, C-reactive protein (CRP), has garnered considerable attention for its role in both promoting and predicting cardiovascular disease and stroke in initially healthy people. It is produced by the liver in response to inflammation, and inflammation has recently been shown to underlie the plaque that forms inside arteries as they clog.

The Duke study is the first to link this combination of negative psychological attributes with higher levels of CRP in people without traditional risk factors for heart disease...

More specifically,

121 healthy men and women were asked to complete standard personality questionnaires in which they described their psychological attributes, including anger, hostility and depression. The volunteers did not have any pre-existing conditions -- such as smoking, high blood pressure, diabetes or heart disease -- that would predispose them to having high CRP levels. High-sensitivity blood tests were then conducted to measure CRP levels.

Respondents who were prone to anger, had high hostility levels, and showed mild to moderate symptoms of depression had two to three times higher CRP levels than their calmer counterparts. The more pronounced their negative moods, the higher CRP levels they had, the study showed.

In addition, the researcher had previously shown a relation between the psychological variables and another inflammatory substance (interleukin-6):

[H]ostile people who exhibit symptoms of depression have higher levels of stress hormones and circulating levels of an inflammatory substance called interleukin 6, another marker of inflammation that has been shown to predict heart disease in initially healthy people.

A number of other studies have demonstrated relationships between psychological stress conditions and disease states that involve the immune system, such as this one from 2006:

Anger And Hostility Speed Up Decline In Lung Power

The authors point out that hostility and anger have been associated with cardiovascular disease, death, and asthma, and that previous research has suggested that changes in mood can have short term effects on the lungs.

Anger and hostility will alter neurological and hormonal processes, which in turn may disturb immune system activity, producing chronic inflammation, suggest the authors.

An accompanying editorial comments that the physiological components of anger and stress overlap, and stress is well known to affect the immune system.

Bottom line: Get control over anger and depression if you want to stay healthy.

Of course, this is all closely related to what I discussed just a couple of weeks ago on stress and weight gain and in particular the extensive research of Robert Sapolsky summarized here.

Additional references:

• Coping With Stress Improves Cholesterol
  
• High Hostility May Predict Heart Disease More Than Other Risk Factors Such as Cholesterol and Smoking
  
• Hostility is among best predictors of heart disease in men
  

Tags: inflammation, stress, anger, hostility, depression, cardiovascular disease, hypertension

Stress and weight gain

There is, apparently, truth to the idea that people under stress may gain weight – and it's not just that people simply choose to escape their problems by eating. And this is only one of the reasons stress isn't good for your general health.

Scientists Discover Key To Manipulating Fat; Pathway Also Explains Stress-induced Weight Gain

In the paper, the Georgetown researchers describe a mechanism they found by which stress activates weight gain in mice, and they say this pathway -- which they were able to manipulate -- may explain why people who are chronically stressed gain more weight than they should based on the calories they consume.

The key to the process that was found is a peptide (small protein) neurotransmitter called neuropeptide Y (NPY). NPY is produced under conditions of stress, as a by-product of the "fight-or-flight" response mediated by the sympathetic nervous system. An animal under conditions of chronic stress will have higher levels of NPY. The hormone was discovered 25 years ago, and earlier research indicates that it acts in the brain to increase appetite. (Although other aspects of the response may suppress appetite, which is why some overly stressed people may be emaciated.) The appetite-suppressing hormone leptin acts by inhibiting the activity of neurons that contain NPY.

What the new research found, however, is that, more importantly, NPY, acting outside the brain in adipose tissue, also alters an animal's metabolism to increase storage of fat:

As part of the study, Zukowska and her team examined the effect of several forms of chronic stress that mice in the wilderness can encounter, such as exposure for an hour a day over a two-week period to standing in a puddle of cold water or to an aggressive alpha mouse, and they conducted the experiments in combination with a regular diet or with a high-fat, high-sugar diet. Stressed animals fed a normal diet did not gain weight, but stressed mice given a high-fat diet did. In fact, the researchers found these mice put on more weight than expected given the calories they were consuming.

"They gained twice as much fat as would be expected, and it was all in their belly area," Kuo said. Stressed versus non-stressed animals ate the same amount of food, but the stressed animals processed it differently, she said, explaining, "the novel finding here is that NPY works on fat tissue, not in the brain."

In part, the research showed that NPY experimentally delivered in a mouse activated a G-protein coupled receptor called (naturally) a neuropeptide Y2 receptor (Y2R). (This is just one of 5 known NPY receptors.) Activation of Y2R was observed to promote storage of fat in adipose tissue:

[The] pathway involves two players -- a neurotransmitter (neuropeptide Y, or NPY) and the receptor (neuropeptide Y2 receptor, or Y2R) it activates in two types of cells in the fat tissue: endothelial cells lining blood vessels and fat cells themselves. In order to add fat selectively to the mice they tested, researchers injected NPY into a specific area. The researchers found that both NPY and Y2R are activated during stress, leading to apple-shape obesity and metabolic syndrome.

So NPY can lead to increased fat storage. But the converse is, happily, also true: blocking the NPY receptor shrinks fat:

Both the weight gain and metabolic syndrome, however, were prevented by administration of Y2R blocker into the abdominal fat.

Metabolic syndrome, you recall, comprises several undesirable elements, such as hyperglycemia, high blood pressure, central obesity, decreased HDL cholesterol, and elevated triglycerides. All of these can lead to more serious health problems, such as diabetes and cardiovascular disease. So there is the possibility that blocking Y2R could be beneficial to humans:

"We are hopeful that these findings might eventually lead to control of metabolic syndrome, which is a huge health issue for many Americans," [the study's senior author, Zofia Zukowska] said. "Decreasing fat in the abdomen of the mice we studied reduced the fat in their liver and skeletal muscles, and also helped to control insulin resistance, glucose intolerance, blood pressure and inflammation. Blocking Y2R might work the same way in humans, but much study will be needed to prove that."

Another account of this research reports expressions of optimism for development of human drugs to control stress-induced health problems:

Stress can be fattening, study finds

Mary F. Dallman of UC San Francisco said in an editorial in the same journal: "A large gap in our understanding of how chronic stressors lead to abdominal obesity has been filled…. Their results were remarkable and have profound implications for new drug development."

But it's not a sure thing. There is another hormone, called PYY, Pancreatic Peptide YY, or Pancreatic Peptide YY_3-36. PYY is structurally similar to NPY and in fact can activate some NPY receptors. It has been found to decrease appetite when it activates NPY receptors in the brain. At least two biotech companies (Amylin and Nastech) have investigated using PYY directly as a drug to induce weight loss. So far this effort has had only mixed results.

Here's another report on the research discussed above: How we can stop stress from making us obese. And here's a blog post that raises some good questions about this research: Scientists Stressed About Weight Loss.

Apart from the effects of NPY, chronic stress can cause a variety of health problems besides weight gain, obesity, and their knock-on effects. Robert Sapolsky of Stanford has done copious research into the ill effects of chronic stress. He points out that the fight-or-flight response of animals in the wild, which is activated during periods of acute danger (predators), and is adaptive in those circumstances, can turn harmful when stress is chronic, as happens frequently with primates such as humans:

Why Do Humans And Primates Get More Stress-related Diseases Than Other Animals?

Why do humans and their primate cousins get more stress-related diseases than any other member of the animal kingdom? The answer, says Stanford University neuroscientist Robert Sapolsky, is that people, apes and monkeys are highly intelligent, social creatures with far too much spare time on their hands.

"Primates are super smart and organized just enough to devote their free time to being miserable to each other and stressing each other out," he said. "But if you get chronically, psychosocially stressed, you're going to compromise your health. So, essentially, we've evolved to be smart enough to make ourselves sick."

Tags: stress, obesity, weight gain, neuropeptide Y