Richard G. Petty, MD

A Virus Linking Depression, Aging and Heart Disease

We have known for a long time that there are close links between depression, aging and heart disease, but the nature of the link has remained elusive. Most of the smart money has been on inflammation, but there could be other candidates.

New research in the journal Brain, Behavior and Immunity has linked an increase in two inflammatory proteins in the immune system with a latent viral infection and proposes a chain of events that might accelerate cardiovascular disease. It is possible that the same process may be involved in a number of other ailments that can afflict us, as we get older. The findings also suggest that chronic depression may play a key role in initiating the cascade that can lead to the development of coronary artery disease.

It has been known for some time that increased levels of the proinflammatory cytokines, TNF-α and IL-6, predict mortality and morbidity. High levels of each of them are found in the plasma and in atherosclerotic lesions of people with cardiovascular disease.

The levels of IL-6 in the body increase as the immune system ages. Some of the IL-6 is generated by immune cells - macrophages - that go to the site of an infection or injury. Earlier work by the team also showed that increases in psychological stress and depression could substantially raise the levels of IL-6 and TNF-α in the body.

Increased stress and depression can also trigger latent viruses to reactivate and begin reproducing inside cells. The viruses of greatest interest are some herpes viruses such as the Epstein-Barr virus (EBV). We know that up to 90% of the people in North America have been infected by EBV by the time they are adults.

If EBV begins to multiply in cells in the body, it produces a protein called dUTpase that, in turn, can stimulate macrophages to make yet more IL-6.

The researchers developed a model to test these linkages by using endothelial cells that line the inside of veins in umbilical cord tissue. I spent years working with these cells myself, and they provide an excellent substrate for examining vascular responses and the interaction between blood vessels and macrophages when exposed to the virus as well as the dUTpase protein.

As expected, the production of IL-6, as well as TNF-a, were increased just as they would be as part of the inflammatory process in the body. Such chronic incidents of inflammation are integral to the onset of atherosclerosis and an array of other diseases.

This work suggests a new way of thinking about how vascular diseases develop. We carry around these latent herpes viruses in our bodies virtually all our lives and periodically they can hurt us as we age, develop depression or, perhaps a nutritional imbalance.

Taken together with the recent data on the physical effects of loneliness, if you want to live a long and healthy life:

• Watch you mood: depression can kill you
• Stay socially engaged: loneliness can be fatal
• Maintain a balanced diet
• Take some physical exercise every day
• Learn – and practice! – some simple stress management techniques. You can obtain some at RichardGPettyMD.com

An Antibiotic to Treat Stroke

It is fascinating to see a medicine or a therapy that is used for one thing being applied in a completely different area. A good example is thalidomide, a drug that was introduced in 1957 to treat morning sickness. It was pulled from the market because it could cause terrible fetal malformations. Years later it was discovered that it could be very helpful in the treatment of multiple myeloma, leprosy and Behcet’s disease.

Now a new study has shown that people treated with the antibiotic minocycline within six to 24 hours after a stroke (cerebrovascular accident) had significantly fewer disabilities.

In the study 152 men and women received either an oral dose of minocycline or placebo for five days following stroke. People who received minocycline were treated on average within 13 hours of the onset of the stroke compared to 12 hours for the placebo group. Patients were followed up for three months.

People treated with minocycline had significantly better outcomes than those treated with placebo. By three months, the minocycline group performed four times better than the placebo group on the National Institutes of Health Stroke Scale, which measures vision, facial palsy, movement, and speaking ability.

Minocycline appears to be neuroprotective and to prevent programmed cell death or apoptosis.

This could turn out to be very important because current stroke treatments only work during the first few hours after the onset of symptoms, and many people do not get to the hospital in time to be treated.

Alzheimer’s Disease: Diabetes of the Third Kind?

Insulin may have some extremely important roles in the mind as well as the body.

Though best known for its role in promoting glucose uptake into cells, insulin has at least five hundred known functions in the human body. For many years nobody was sure whether insulin was important to the brain: neurons in the brain are unusual in that they do not need insulin to enter them. But then we discovered that insulin acts on other important metabolic processes in neurons. In the brain it also does duty as a chemical messenger and as a growth factor, and brain insulin signaling is crucial for the creation of memory. Over the years a number of theorists have suggested that some neurological and psychiatric illnesses could be a result of disturbances in insulin-related processes in the brain.

It is now beginning to look as if they may have been correct.

Some recent evidence has suggested that Alzheimer’s disease and diabetes mellitus share a number of common pathways and Alzheimer’s disease is associated with peripheral insulin resistance.

New research has been published by investigators from Northwestern University in the FASEB Journal - the journal of the Federation of American Societies for Experimental Biology –  that may finally nail down the reason why insulin signaling may stop working in Alzheimer’s disease.

The research team used mature cultures of neurons from the hippocampus of the brain to study synapses – the connection between neurons - that have been implicated in learning and memory mechanisms. They wanted to examine the effect of a toxic protein, known to attack memory-forming synapses, that is called  “ADDL” for "amyloid ß-derived diffusible ligand." ADDLS are small, soluble aggregated proteins that accumulate in the earliest stages of Alzheimer’s disease. The researchers had previously found that ADDLs bind very specifically at synapses, which in turn initiates deterioration of their function, shape and composition. They now went on and studied the synapses and their insulin receptors before and after ADDLs were introduced. Regions of the nerve with normal numbers of insulin receptors have no ADDL binding, but when the ADDLs are added they remove insulin receptors from nerve cells, effectively making them insulin resistant.

And an insulin resistant neuron cannot participate in the formation of memories.

This finding implies that there is a fundamental connection between diabetes and Alzheimer's disease, and this may in turn help us to see whether existing diabetes treatments might protect neurons from ADDLs and improve insulin signaling in people with Alzheimer's disease.

The first type of diabetes is Type 1, a.k.a. insulin-dependent or juvenile onset. The second is Type 2, a.k.a. non-insulin-dependent diabetes. So is Alzheimer's Type 3?

It has also been known for some time that physical exercise is one of the factors that may help reduce the chance of developing Alzheimer’s disease, and we may now have a mechanism by which it can help.

This is an extraordinarily interesting and important discovery that should lead to a whole new research angle, perhaps with medicines that are already available.

Howard Hughes Medical Institute Joins the Open Access Revolution

The Howard Hughes Medical Institute (HHMI) has agreed to support Springer's Open Choice program. What that means is that if articles are accepted for publication after a process of rigorous peer-review, they will immediately be published with full open access and deposited in repositories such as PubMed Central, at a flat-rate fee per article of $3,000. Springer's Open Choice program applies to all its journals.

HHMI has a strong commitment to ensuring public access to original research articles. Beginning with papers submitted for publication after January 1, 2008, HHMI will require its scientists to publish their original research articles in journals that allow the articles and supplementary materials to be made freely accessible in a public repository within six months of publication.

HHMI is the largest private funder of biomedical research in the United States and commits more than $500 million a year for research and distributes $80 million in grant support for science education.

HHMI investigators already publish a significant number of research articles in open access journals or in journals with open access options. Under the new policy, HHMI will pay up to $2,000 in open access charges per article with the balance coming from laboratory budgets or other sources.

It is wonderful that one of the largest and most prestigious research institutes in the world, is actively supporting open-access publishing and backing up their words with significant funding

Deep Voices, Sexual Attraction and Children

I know that there are going to be a ton of exceptions, but I was extremely interested to see a study in the journal Biology Letters that seems to indicate that a deep male voice may attract women more than a great physique or an attractive face. Men with deep voices are also much more likely to have more children than men who do not have deep voices.

The investigators used an interesting analogy, sating that a man's deep voice is a bit like a peacock's tail: it has no survival value, but attracts the female of the species. Testosterone masculinizes the voice at puberty.

The research team interviewed 52 women and 49 men aged 18-55, from the Swahili–speaking Hadza tribe in Tanzania. They chose the Hadza tribe because their lifestyles reflect those of our hunter-gatherer ancestors. The females gather berries and search for wild plants. The males collect honey and hunt animals. Even though the Hadza are monogamous, extra-marital sex is common, but there is no birth control.

During the interviews, which took place in Swahili, the voices of the men and women were recorded. On studying the recording later they found that the deep voiced men had fathered more children than the non-deep voiced men. The man with the deepest voice had ten surviving children, while the one with the highest pitched voice had three.

Coren Apicella, the lead author, suggested that perhaps the males with the lower pitched voices had higher testosterone levels, which attracted them more to females or made them more attractive to them. It is also possible that men with higher testosterone levels start reproducing earlier in life. They may also be better hunters, since testosterone may have an impact on muscle mass, and  a better hunter would bring more food, allowing their wives to have shorter inter-birth intervals. 

It is possible that if vocal dimorphism evolved partly due to mate selection, then  in the past men and women may have had more similar voices.


I don’t suppose that anyone is going to be too interested to hear this, but your humble reporter has always had a very deep voice…

Taking Action on Food Additives and Hyperactivity

Regular readers will remember my recent article concerning food additives and hyperactivity in children.

I have just read that he British Food Standards Agency (FSA) has been accused by campaigners of "chickening out" of banning additives linked to hyperactivity in children even though they funded the research that was published in the Lancet.

After the research was published, the FSA issued updated advice that eliminating the artificial colorings from the diet might have some beneficial effects in hyperactive children.

But critics said it did not go far enough and several environmental and children's campaign groups, including the National Union of Teachers, called on the watchdog to extend that advice to all children since the additives posed a threat to psychological health.

The FSA responded by saying that the evidence was not strong enough to justify a ban and it would wait for the European Food Safety Authority (EFSA) to make a decision on use of additives in food.

EFSA says that it is considering the research as a matter of urgency and will be making an initial response within the next month.

We shall see what they have to say.


These were the main additives incriminated in the Lancet study:
Sunset yellow (E110) - Coloring found in some drinks
Carmoisine (E122) - Red coloring in jelly
Tartrazine (E102) - New coloring in some frozen and carbonated drinks
Ponceau 4R (E124) - Red coloring
Sodium benzoate (E211) - Preservative
Quinoline yellow (E104) - Food coloring
Allura red AC (E129) - Orange / red food dye

The Neuronal Shield

Sometimes Nature does our experiments for us, and nobody - especially any animals - need to get hurt at all.

Diabetes mellitus is one example, in which heart disease, arteriosclerosis and stroke are many times more common than they are in the general population, and give us a perfect place to start looking at some of the causes of arterial diseases in general.

Another, and far more rare, example is a group of brain diseases called lissencephaly, in which whole layers of the cerebral cortex fail to find their homes and develop. The result is a brain that has a fairly smooth surface, rather than being covered in the complex hills and valleys (“gyri” and “sulci”) that cover the surface of the healthy brain. People with lissencephaly usually have quite severe mental retardation, motor problems, muscle spasms and seizures. What normally happens during embryonic development is that the six main layers of the cerebral cortex are generated by neuronal progenitor cells that migrate long distances before they finally find their correct place and settle down. At the beginning of brain development the cells look like an unruly mob trying to find their seats at a concert. Eventually they find their spot, settle down and get to work. The precise spatial organization of these layers of cells is essential to normal cortical functions.

Though lissencephaly is rare, there are other disorders, including some forms of epilepsy and some types of schizophrenia that also result from abnormal migration of nerve cells during the development of the brain.

Researchers from the Mouse Biology Unit of the European Molecular Biology Laboratory (EMBL) in Italy have now discovered that a protein called n-cofilin, that helps organizing the cells' skeleton is crucial for preventing such defects. In the current issue of Genes & Development they report that mice lacking n-coffin show many of the classic signs and symptoms of lissencephaly.

The skeleton of a cell consists of constantly growing and shrinking filaments that function like strings and struts to give the cell shape and stability, and it is largely responsible for the migration of neurons in the developing brain. N-cofilin interacts with actin - one kind of skeletal filaments - and helps to disassemble them into their individual building blocks. Interfering with this filament remodeling impairs the cell's ability to move and that blocks migration of neurons during cortical development.

N-cofilin also controls the fate of neural stem cells that are involved in development of the cortex. If it is absent, stem cells stop moving and re-new themselves instead of differentiating. This imbalance depletes the pool of neuronal progenitors cells so that fewer cells can be made to build a complete and functional cortex. The study provides the first proof that proteins affecting actin filament dynamics are involved in neuronal migration disorders.

It is remarkable that a single gene can be so important in the development of the brain, and it opens up new fascinating possibilities for treatment.

Low Testosterone May Shrink Your… Brain

It is almost forty years since Fernando Nottebohm first began to describe some of the dynamic changes that occur in the brains of songbirds as the seasons change. Every year some regions of the brain grow in response to changes in ambient light levels and others regress. There are marked seasonal changes in the brains of fish, reptiles, amphibians, birds and even some mammals such as gerbils, mice and perhaps even in humans. But the magnitude of the changes in birds far outweighs any other species. It is hoped that that understanding the mechanism controlling that change may help us to develop treatments for age-related degenerative diseases of the brain such as Parkinson's and dementia.

Researchers from the University of Washington and the University of California, Berkeley, have published  some interesting new data in the Proceedings of the National Academy of Sciences. They report a striking shrinkage in the size of the brain regions that control singing behavior of Gambel's white-crowned sparrows. This transformation is triggered by the withdrawal of testosterone and can be seen within 12 hours. The study is the first to report such rapid regression of brain nuclei caused by the withdrawal of a hormone and a change in daylight conditions in adult animals.

The research protocol was designed to mimic the natural seasonal changes that occur in the brains of the sparrows. Their song-control regions expand in the spring and summer leading up to the breeding season, as they use songs to establish territories and attract mates in Alaska. Later in the summer, as the birds get ready to migrate back to California, the same brain regions shrink.

To better understand what happens in the sparrows' brain, the researchers received federal and state permits to capture 25 of the migrating male birds in Eastern Washington. They then housed the birds for 12 weeks before exposing them to 20 days of long-day conditions comparable to the natural lighting the sparrows would experience in Alaska during the breeding season. The birds were also implanted with testosterone.

At the end of 20 days, six of the birds were euthanized and the remaining 19 were castrated and testosterone implants were removed so there would not be any circulating testosterone in their systems. After 12 hours five more birds were euthanized and the remainder were euthanized at 2, 4, 7 and 20 days.

The researchers found that the size of the high vocal center (HVC) region decreased 22 percent within 12 hours after the withdrawal of testosterone and that the number of neurons in this song-control region fell by 26 percent after four days. In addition, the size of two other song-control regions called Area X and the RA significantly regressed after 7 and 20 days.

Much as I dislike animal experiments of any kind, it is invaluable to have an animal model system in which we can observe predictable neurodegeneration. As men age, circulating levels of testosterone decrease, and other research has shown that this decline may contribute to cognitive impairment.

This is an important new approach to understanding the interplay between nerve cell degeneration and hormones.

Molecules of Loneliness

It is well known that our social environment has a major impact on our health, wellness and longevity. Lonely, socially isolated adults have a higher mortality than those who are socially engaged.

There has been a lot of speculation about the factors involved, and there is a fascinating study published in the current issue of the journal Genome Biology.   

Researchers from UCLA identified a distinct pattern of gene expression in the white blood cells of people who experience chronically high levels of loneliness. The findings suggest that feelings of social isolation are linked to alterations in the activity of some of the genes that drive inflammation providing a molecular framework for understanding why social factors are linked to an increased risk of heart disease, viral infections and cancer.

Lonely people suffer from higher mortality than people who are not, and the debate has been whether that risk is a result of reduced social resources, or whether it is biological.

In this study the researchers used DNA microarrays to survey the activity of all known human genes in white blood cells from 14 individuals in the Chicago Health, Aging, and Social Relations Study. Six participants scored in the top 15% of the UCLA Loneliness Scale, a widely used measure of loneliness that was developed in the 1970s; the others scored in the bottom 15%. The researchers found 209 gene transcripts that were differentially expressed between the two groups, with 78 being over-expressed and 131 under-expressed. Genes over-expressed in lonely individuals included many involved in immune system activation and inflammation. At the same time, several other key gene sets were under-expressed, including those involved in antiviral responses and antibody production.

The first author on the study s Steve Cole, an associate professor of medicine in the division of Hematology-Oncology at the David Geffen School of Medicine, and a member of the UCLA Cousins Center for Psychoneuroimmunology, and he had this to say:

"What this study shows is that the biological impact of social isolation reaches down into some of our most basic internal processes the activity of our genes.
We found that changes in immune cell gene expression were specifically linked to the subjective experience of social distance. The differences we observed were independent of other known risk factors, such as health status, age, weight, and medication use. The changes were even independent of the objective size of a person's social network."

“We found that what counts at the level of gene expression is not how many people you know, it's how many you feel really close to over time.”

This study was supported by the National Institutes of Health, the Mind, Body, Brain and Health Initiative of the John D and Catherine T MacArthur Foundation, the Norman Cousins Center at UCLA, the John Templeton Foundation, and the James B Pendelton Charitable Trust.

Although small, this is remarkable and shows how much nature not only abhors a vacuum, but also dislikes isolation. We are social animals and anything that gets in the way of that will likely lead to a very poor outcome.

It is fitting that Norman Cousins, for whom the UCLA center is named, had this to say:
“The eternal quest of the individual human being is to shatter his loneliness.”

“The most terrible poverty is loneliness and the feeling of being unloved.”
-Mother Teresa of Calcutta (Albanian-born Indian Nun, Humanitarian and, in 1979, Winner of the Nobel Peace Prize, 1910-1997)

Sex, Handedness and the Brain

I have commented before on my longstanding interest in handedness and laterality, as well as gender differences in the brain. A recurrent question when we look at both of them is whether culture has any role in the development of either. Are some of the differences in male and female brains driven by educational opportunities and cultural expectations, or is there something innate about them?

A recently published paper in PLoS ONE reports finding both sex and handedness influences on the relative size of the corpus callosum in Capuchin monkeys.

Capuchin monkeys are playful, inquisitive primates best known as the “Organ Grinder” monkeys. They have great manual dexterity, complex social behavior, and cognitive abilities. The new research now shows that just like humans, they display a fundamental sex difference in the organization of the brain, specifically in the corpus callosum, the band of white matter that connects the two hemispheres of the brain.

In the study, thirteen adult capuchins underwent magnetic resonance imaging of the brain to determine the size of their corpus callosum. The monkeys were later given a task to determine hand preference. The authors' results led them to conclude that, as in humans, male capuchins have a smaller relative size of the corpus callosum than females, and right-handed individuals have a smaller relative size of the corpus callosum than left-handed individuals.

As the two hemispheres show greater independence of function, the relative size of the corpus callosum is expected to be smaller. This has been documented in humans, and same pattern was found in capuchins.

This finding may be related to hemispheric specialization for complex foraging tasks that require the integration of motor actions and visuospatial information. In the wild, capuchin monkeys live in trees as well as on the ground, and they are known to be very good at capturing small swift prey such as birds, lizards, and squirrels.

Schizophrenia and Evolution

Schizophrenia remains one of the cruelest illnesses ever to afflict humanity. There are more theories about it than any other problem, and we may be getting closer to understanding why it seems to occur only in humans, and at roughly the same rate throughout the world. One idea is that the genetic predisposition to schizophrenia might have evolved as a secondary consequence of selection for human cognitive traits. As humans have evolved so has the brain, and it has become more lateralized, so this might explain the association between schizophrenia and handedness.

Several genes with strong associations to schizophrenia have evolved rapidly during human evolution, according to new research in the Proceedings of the Royal Society B this week.

In support of the cognition/schizophrenia hypothesis, researchers Dr Steve Dorus from the University of Bath, who worked with Dr Bernard Crespi from Simon Fraser University in Canada and Dr Kyle Summers from East Carolina University in the United States found that these genes had been positively selected.

They analyzed the molecular evolution of the 76 genes that have the strongest genetic association with the disorder. They surveyed human polymorphisms for discrete changes in the human genome that vary between individuals, in order to try and track very recent selective events within specific human populations. They also compared genes between mammalian species to identify selection on primate lineages salient to the evolution of humans and the disorder.

Amongst the genes for which they found positive selection were three genes that have the best functional or reproducible associations with the disorder: disrupted in schizophrenia (DISC1), dystrobrevin-binding protein 1 (DTNBP1) and neuregulin 1 (NRG1).

The selective forces underlying adaptive evolution of these genes remain largely unknown, but these findings are consistent with the hypothesis that schizophrenia is a maladaptive by-product of adaptive changes during human evolution, perhaps associated with creativity and human cognition.

Acupuncture for Hypertension

In China and Japan I have seen acupuncture used to treat just about everything, with varying degrees of success.

Researchers from Erlangen in Germany have published a randomized single blind trial comparing acupuncture with sham needling in the journal Circulation. The results suggest that acupuncture may decrease blood pressure in hypertensive patients by a similar amount to that achieved using medication.

The investigators randomized 160 outpatients (mean age 58) with uncomplicated, mild to moderate hypertension to six weeks of acupuncture performed by Chinese medicine practitioners (trained in China), or to a sham procedure. Those on hypertensive medication continued taking it.

Patients were assigned to one of four patterns of hypertension, based on TCM diagnosis. Those in both trial arms underwent 22, 30-minute treatment sessions over a six-week period. During each session, three acupuncture points were needled bilaterally for 20 minutes. In the active treatment group, the points were chosen according to traditional Chinese medical diagnosis. Sham treatment consisted of needling points that according to Chinese medical theory would have no effect on blood pressure

Twenty-four hour ambulatory systolic and diastolic blood pressures were significantly reduced from baseline in the acupuncture-treated patients (by 5.4 mmHg and 3.0 mmHg, respectively). No significant decrease was seen in the sham-treated patients. The extent of blood pressure reduction observed was comparable to that seen with ACE-inhibitor monotherapy or aggressive lifestyle changes. However, blood pressure returned to pretreatment levels within 12 weeks of treatment cessation, leading investigators to conclude that ongoing acupuncture treatments would be required to maintain the beneficial effects.

This in an interesting study, but I agree entirely with some of the comments made in an accompanying editorial by Fiona Turnbull and Anushka Patel from the George Institute for International Health in Sydney, Australia.

Randomized trials of acupuncture have been conducted since the 1970s, but many were of poor quality, and did not even include control groups. In 1995 the World Health Organization published clear guidelines for clinical research on acupuncture, which included detailed information relating to the nature of control groups and blinding in randomized controlled trials. More recently, a National Institutes of Health Consensus Development Panel stated that the acceptance of acupuncture as a reliable therapeutic choice would depend on its evaluation using study designs that could withstand careful scientific scrutiny.

The whole issue of “sham” acupuncture remains problematic. Not only are we doing something physical. But the people administering the acupuncture know whether or not they are needling an “active” point, an even if they say nothing, they may well communicate what they are doing. There is also a more subtle point that is not raised in the editorial. A good acupuncturist does not just stick in a needle. He or she waits for the appearance of a characteristic and subjective needle sensation that tells him or her whether the needle is in the correct position.

Acupuncture studies are, simply for logistical reasons, usually fairly small and this one was no exception. And that brings us to the other point. Most forms of alternative and complementary treatment are very time consuming, and need a lot from a patient who has to show up for multiple treatments, for which he may be paying himself.

If a course of acupuncture treatment can bring about some long-term change or re-balancing in a person that might be worthwhile, but in this study the blood pressure went back up once the treatment was discontinued.

Mother’s Dreams

Having a baby is one of the Really Big events in life, and it is no surprise that both pregnancy and birth have a major influence on the structure and content of a mother’s dreams.

It is also not surprising that many of the dreams have a strong negative component to do with maternal responsibility, or depicting the new infant in dreamed situations of danger. These dreams can cause anxiety that can spill over into wakefulness. A new study from Montreal published in the journal Sleep has added something new: these kinds of dreams may be accompanied by complex sleep behaviors such as motor activity, speaking and expressing emotions.

The study from the Sleep Research Centre at the Hôpital du Sacré-Coeur de Montréal in Montréal, Québec, Canada, focused on 273 women, who were divided into three groups: postpartum, pregnant, and women who had not given birth. The subjects completed questionnaires about pregnancy and birth factors, personality and sleep. They were also interviewed and asked about the prevalence of recent infant dreams and nightmares, associated behaviors, anxiety, depression and other psychopathologic factors.

• The percentage of women in all groups who recalled dreams ranged from 88-91%
• Postpartum and pregnant women recalled infant dreams and nightmares with equal prevalence, but more postpartum women reported they contained anxiety (75%) and the infant in danger (73%) than did pregnant women (59%)
• Motor activity was present in twice as many postpartum (57%) as pregnant (24%) or non-pregnant (25%) women
• Expressing emotion was more prevalent among women without children (56%) than postpartum women (27%), but was not different from pregnant women (37%)
• Speaking while asleep was equal among the three groups (12-19%)
• Behaviors were associated with nightmares, dream anxiety and, among postpartum women, post-awakening anxiety (41%), confusion (51%), and a need to check on the infant (60%)

Most pregnant women experience daytime fatigue primarily because the quality of their sleep tends to be worse. Physical discomfort and awakenings are common, particularly during the third trimester.

Snoring often increases during pregnancy and obstructive sleep apnea may develop as the pregnancy progresses.

Two other sleep disorders that are more common during pregnancy are restless legs syndrome (RLS) and sleep related leg cramps. RLS affects nearly 25% of pregnant women and may be related to low iron stores. Leg cramps occur in about 40% of pregnant women, although they usually clear up after delivery. They tend to go away after delivery.

It is easy to understand these dreams from an evolutionary perspective. Though there is also a small literature on mothers who get intuitive flashes about their distressed infants. I have followed this work for many years. When I was an infant I chocked on a banana, and my mother who was some way off “saw” it happening in her mind’s eye and rushed in to find a very small RP who had already turned blue. She swore to her dying day that the tale was true.

And I still cannot eat bananas.

Food Additives, Food Colorings and Hyperactivity

Regular readers will know that I am very interested in the impact of food and food additives on cognition and behavior. Unfortunately it is a field that has generated more heat than light, with some patients associations and commercial organizations providing rather unbalanced assessments about the whole issue and how best to deal with it.

What we do on this website is to provide you with information that has a solid foundation. A good example is a new study published this week in the Lancet by a team of researchers from Southampton University in the United Kingdom. (The full article is available here).

An alarming number of foods contain artificial food color and additives (AFCAs), and there has been a great deal of concern about their potential impact not only on behavior, but also on the developing brain.

A study published three years ago examined the impact of specific mixtures of additives on hyperactivity in three-year-old children. It was an important piece of work, but the worry was that the study focused on parental rather than objective ratings of hyperactivity. Though parents are usually very good at observing their own children, most of us also have our own ideas about the things that may cause problems.

In this new study was sponsored by the British Food Standards Agency and the researchers looked at the effects of additives on changes in children's behavior in a community-based, double-blinded, placebo-controlled, crossover trial.

The study involved 153 children aged 3, plus 144 children aged 8-9. They were given either a drink containing sodium benzoate plus one of two AFCA mixes, or a placebo drink. The two AFCA mixes contained:

• Mix A - included 20 mg of artificial food colorings (5 mg sunset yellow [E110], 2⋅5 mg carmoisinetartrazine [E102], and 5 mg ponceau 4R [E124, and 45 mg of sodium benzoate [E211]. (These were the same ingredients used in the previous study). [E122], 7⋅5 mg
• Mix B was designed to be what the average 3 year-old and 8-9 year old may be consuming today, and included 30 mg of artificial food colorings (7⋅5 mg sunset yellow, 7⋅5 mg carmoisine, 7⋅5 mg quinoline yellow [E110], and 7⋅5 mg allura red AC [E129]) and 45 mg of sodium benzoate.

The children's behaviors were measured by a “global hyperactivity aggregate” (GHA) that is based on teachers' and parents' ratings. The older children also received a computerized test for attention.

The main findings were that:

• Mix A had a significant adverse effect on children in GHA for all the 3 year-olds, compared to the placebo.
• Mix B produced mixed results for 3 year-olds
• Both Mix A and Mix B had significant adverse effects on the 8-9 year olds, compared to the 8-9 year-olds on the placebo
• Children vary greatly in their levels of adverse effects from consuming AFCA

So this new research indicates that foods containing AFCAs may fuel hyperactive behaviors in children from early to middle childhood. An important point is that AFCAs may impact any child: the effect is not restricted to children who are already hyperactive or have attention-deficit/hyperactivity disorder (ADHD). The problem with hyperactivity is not so much the challenge of living with an overly energetic child, but rather the impact of hyperactivity on development and education, particularly on reading skills. The hyperactive child may not get the full benefit of a conventional education.

The researchers do not yet know whether their findings apply to older children. But they raise the question whether complete withdrawal of AFCAs from the food supply might decreases the overall rate of hyperactivity in the population.

However, they ask whether the general levels of hyperactivity in children in the general population might not go down significantly if AFCAs were withdrawn completely.