Richard G. Petty, MD

Psychiatry Below the Neck

There is more and more evidence that schizophrenia and bipolar disorder and perhaps also major depressive disorder, are illnesses affecting the whole body and not just the brain and mind.

It has been known for over a century that some physical problems, including type 2 diabetes mellitus, obesity, cardiovascular diseases and some forms of cancer appear to be more common in people with major mental illnesses. All of this was known long before the current concerns about obesity, diabetes and some antipsychotic medicines. It is also clear that the physical problems cannot just be explained away by social deprivation and poor lifestyle choices.

The new understanding of mental illness as a systemic problem, opens up some extraordinary opportunities for treatment and perhaps even for prevention. In some new research due to be published next month, investigators have identified some abnormal proteins in the liver and on red blood cells that are similar to some abnormal proteins already identified in the brain.

These proteins are primarily involved in energy metabolism in cells and in protection against oxidative stress. The implication from this is that schizophrenia and many of the associated health problems may be a consequence of impaired energy metabolism together with damage by free radicals.

You will see why this is so exciting: it looks as if we have an entirely new way of approaching, treating and perhaps preventing the most serious of mental illnesses.

Another Nail in the Coffin of BMI


In August I outlined some of our reasons for believing that the most common measure of overweight and obesity – the body mass index (BMI) – can be very misleading and should probably be abandoned, or at least consigned to the back burner.

A team at the Hammersmith Hospital in London led by Professor Jimmy Bell has been using a novel type of MRI scan to locate the distribution of fat in the body. The problem is that 40% of the population has “bad” fat around some of their internal organs including the heart, liver or pancreas, even though many appear thin. So even though they may look slim, they may still be at risk of conditions like insulin resistance, diabetes and hypertension because of this hidden fat.

As we have said before, from a health perspective, it is the distribution of fat that is all important, rather than just the amount of it. This study confirms what metabolic physicians have been saying for years: BMI gives you the wrong idea about how much fat you have.

Once you know about the distribution of your fat, we can design precise lifestyle changes to work on it. As an example, the strategies that we use for overall weight management are not the same as the strategies that we use for reducing intra-abdominal fat. There are very good physiological reasons why diet does little to reduce the fat around organs. It is there to provide fuel during exercise, so specific exercises are the way to rid yourself of this internal fat.

At the moment there are very few centers that can do this kind of scanning, but with the growing evidence of its importance, that is likely to change. In the meantime, be aware that aerobic exercise and strength training, particularly if it involves the large muscles of the back trunk and lower limbs is the quickest way to rid yourself of these dangerous fat deposits.

Fat in itself is essential for normal health, but fat in the wrong places can be a killer. And BMI tells you nothing about the fat lurking in the hidden parts of your anatomy.

Carpal Tunnel Syndrome and Diabetes


Carpal tunnel syndrome is a relatively common neurological problem in which the median nerve is compressed in the wrist.

The classical symptoms are:

  • Tingling, numbness or burning in the fingers or hand, especially thumb, index, middle or ring fingers, but not your little finger. It is most typically present on waking, but can occur after using the hands. Some people “shake out” their hands to relieve their symptoms.
  • Pain radiating or extending from the wrist up the arm to the shoulder or down into you’re the palm or fingers, especially after forceful or repetitive use.
  • A sense of weakness in the hands and sometimes a tendency to drop things
  • Numbness, especially in the tips of the thumb, index, middle and ring fingers.
  • Eventually the small muscles that control the thumb, index and middle fingers can weaken and atrophy.


In many people there is not obvious cause, although it is more common in women approaching menopause, and these days it can be one of the problems associated with using a computer mouse of keyboard for long periods. Every student of health care learns that there is a great long list of causes including:

  • Pregnancy
  • Rheumatoid arthritis
  • Trauma
  • Hypothyroidism
  • Diabetes
  • Amyloidosis
  • Acromegaly
  • Myeloma
  • Tumors

Although I was taught about carpal tunnel syndrome not just as a cause but also as a predictor of diabetes more than 30 years ago, it has been forgotten by some non-specialists.

There is some new research from King’s College in London that has suggested that carpal tunnel syndrome may be a harbinger of diabetes.

As many as 20% of people with diabetes have a compression neuropathy such as carpal tunnel syndrome, and in people with limited joint mobility – a complication of diabetes – the incidence may be as high as 75%. The new research indicates that carpal tunnel syndrome may precede the diagnosis of diabetes by up to 10 years. The work was based on an analysis of 2,655 people who were diagnosed with type 2 diabetes in 2003-2004. The researchers excluded people with other known risk factors for carpal tunnel syndrome. The relative risk for subsequently developing diabetes was 1.63.

This research shows once again that diabetes can sometimes make its presence felt years before it has been formally diagnosed. A study published in 2003 found that 56% of people with peripheral neuropathy of unknown cause actually had abnormal glucose tolerance tests.

Earlier this year, researchers form the Netherlands did a retrospective review of 516 people with carpal tunnel syndrome, and found only two people with diabetes. They therefore recommended that routine screening for diabetes was not worthwhile in otherwise typical carpal tunnel syndrome.

I disagree with them.

I think that it would be wise to screen people with carpal tunnel syndrome for any disturbances of glucose metabolism, including insulin resistance, and if they are at a particularly high risk of developing diabetes, it would be worth going ahead and doing a glucose tolerance test. We don’t often do them these days, but this would be one of those times.

Hostility and Insulin Resistance

Insulin resistance – a reduction in the body’s ability to respond to insulin – is something that should interest and concern all of us. Not only are a third of Americans insulin resistant, with much higher rates in people of African and Indian heritage, but also insulin resistance is the major predictor of the development of type 2 diabetes and of coronary artery disease.

We already knew that stress and certain personality factors, including hostility can be associated with insulin resistance. Now new research from The Cleveland Clinic in Ohio has clarified the association.

The study involved 643 men with an average age of 63.1 years, and the findings are published in the current issue of Psychosomatic Medicine.

The researchers measured the subjects’ urine levels of norepinephrine. Norepinephrine is one of the objective indicators of stress. The researchers used standard rating scale – the Minnesota Multiphasic Personality Inventory and the Cook-Medley Hostility scale – to measure hostility. Insulin resistance was measured using some highly validated methods: the homeostatic model assessment index; 2-hour post-challenge glucose and insulin levels. The study had to be large because some many things can influence insulin resistance: nine other common variables had to be factored in to the analysis.

The study found that there was a statistical interaction between hostility and stress level in predicting insulin resistance. More hostile people do not always have worse insulin resistance, but they do when they are under stress, particularly if it is high level and sustained stress.

The team also found that not all components of hostility are related to insulin resistance. For instance, cynicism is a personality trait that is strongly related to insulin resistance.

We do not know if stress management techniques can reduce the risk of developing insulin resistance in these high-risk people, but it is likely that they will.

Yoga, tai chi ch’uan, meditation, psychotherapy may all be helpful. The best results of all have been to combine one or other of these with homeopathy, flower essences and spiritual counseling. We have little empirical research for these combined approaches, but a great deal of clinical experience that they may be beneficial.

If you notice that you or someone around you has a hostile, cynical way of handling stress, let them know that they are at high risk of developing a physical illness, but that there is a great deal that they can do for themselves before they fall off the cliff.

Chloroquine, Insulin and Inflammation

Your humble reporter was fascinated to read about some new research using the anti-malarial agent chloroquine as a potential treatment for the insulin resistance syndrome.

I have a personal reason for being interested. Hypoglycemia (low blood glucose) is an occasional feature of treatment with chloroquine and in 1980 a study first indicated that chloroquine might slow the break down of insulin by the liver. In the early 1980s there were a flurry of papers indicating that chloroquine did some subtle things to insulin and insulin receptors in many tissues. So we came up with the idea of measuring its effects in humans. There was a memorable occasion on which I was doing an outpatient clinic with an intravenous line in my arm. (English doctors are well known for doing experiments on themselves: I had a professor in medical school who said that you should never do to a patient what you haven’t had done to yourself. I shall leave it to you, gentle reader, to wonder if I’ve tried everything….).

So there I am doing my clinic when, around 11AM I begin to feel really strange: my glucose level was almost unrecordable and my insulin level was off the chart. Nothing that couldn’t be solved with a large dollop of sugar, but it made me very sympathetic to people who get hypoglycemic from their regular treatments.

Sometimes Nature does our experiments for us: we did a lot of work on diabetes because it is associated with high rates of vascular disease. So understanding the mechanisms by which diabetes does that may help illuminate some of the cellular disturbances underlying arteriosclerosis in general. We are also interested in the few illnesses in which a single disturbed gene may lead to a definable set of signs and symptoms. There is a rare illness known as ataxia telangiectasia in which sufferers have a high risk of developing some cancers particularly lymphomas and leukemia. People with the illness are very sensitive to ionizing radiation, have a specific type of immune deficiency, degeneration of parts of the brain related to muscle function and coordination and they age prematurely. More than ten years ago it was discovered that a single gene – ataxia-telangiectasia mutated (ATM) gene – was responsible for the illness. The gene is responsible for producing a protein that recognizes damage to DNA. It now seems that ATM may also be linked to metabolic and cardiovascular diseases. It does this by inhibiting a protein called JNK, a stress kinase involved in inflammation with related effects in insulin resistance and atherosclerosis. So to everyone’s surprise a gene that can cause a rare disease can also cause insulin resistance.

In the November issue of Cell Metabolism, researchers at Washington University School of Medicine in St. Louis and St. Jude Children’s Research Hospital in Memphis, Tennessee report that a small dose of chloroquine eased many symptoms of metabolic syndrome in mice, reducing blood pressure, decreasing hardening and narrowing of the arteries and improving blood sugar tolerance. The results suggest we may only need very low and perhaps infrequent doses of chloroquine to achieve similar effects in humans. Both insulin and chloroquine activate the ATM gene.

This adds to the data that some of the metabolic dysfunctions triggered by obesity may be linked to the inflammatory responses that go wrong in autoimmune disorders like arthritis and systemic lupus erythematosus.

And an older treatment for rheumatoid and lupus just happens to be chloroquine.

Chloroquine itself has some side effects, but this is important information that will help us design more effective and carefully targeted holistic treatments for both metabolic disturbances and inflammatory conditions. All in all, very good news indeed.

Aerobic Exercise, Diet and Abdominal Fat

Most of us are probably aware of the difference between fat inside the abdomen – “intra-abdominal,” also called visceral fat – and fat on the hips or the outside of the abdomen. The fat inside the abdomen is associated with insulin resistance, diabetes and at least a dozen other medical problems. This fat is also covered in cortisol receptors and breaks down and reforms extremely rapidly. By contrast the fat on the outside of the body has relatively few metabolic consequences until the amount of it becomes extreme.

Excess fat in general is not a good idea, but it is the intra-abdominal fat that is the best target for treatment.

New research has shown that the addition of aerobic exercise to a standard dietary weight loss program can preferentially reduce abdominal fat in overweight people.

The investigators did a twenty week prospective study in which looked at 45 obese women with an average age of 58 years. During the study the participants bought their own breakfast in consultation with a dietitian, but had their lunch and dinner prepared by the kitchen staff of the hospital. They were either told to continue with their normal routine of daily activities, or to do low-intensity or high-intensity aerobic exercise. The investigators not only did all the standard measurement on their volunteers, they also did fat biopsies and measured the size of the fat cells.

They all lost weight, but in the people who did the high-intensity aerobic exercise, they also had a reduction in the size of the fat cells in subcutaneous tissue taken from the abdomen.

This is interesting, but it’s necessary to sound a note of caution about the experiment: the investigators were measuring subcutaneous fat cells rather than the all important intra-abdominal fat cells. The trouble with measuring those is simply getting at them. It is not easy trying to get fat out of the abdomen without some invasive procedures.

Renal Cell Carcinoma and Bread

Renal cell carcinoma (RCC) is the most common type of kidney cancer, and accounts for 2 percent of all adult cancers. It has been known for some time that diet plays a role in RCC risk, but attempts to identify which foods have harmful or beneficial effects have been inconclusive.

The smart money has been on foods that elevate insulin levels, because RCC is one of the cancers associated with obesity, and some RCC cell lines grow when exposed to insulin or insulin-like growth factors.

A new study by researchers form the Institute of Pharmacological Research "Mario Negri" in Milan, conducted a large case-control study of 2301 Italians. They found a significant association between high bread consumption and renal cell carcinoma. Eating a lot of pasta and rice may also raise the risk, while eating many vegetables may lower the risk. The study published online October 20, 2006 in the International Journal of Cancer, the official journal of the International Union Against Cancer (UICC), and is available via Wiley InterScience.

The researchers enrolled 767 adults diagnosed with RCC and 1534 controls who did not have the disease between 1992 and 2004. Two controls were matched to each case by gender, age range, and location. The researchers collected sociodemographic information, height, weight, lifestyle habits and personal and family medical history from each participant. They also administered a 78-item food frequency questionnaire which asked about the average weekly consumption for each item over the previous two years. They then performed statistical analyses to discover odds ratios (OR) with a 95 percent confidence interval.

They found a significant direct association was observed for bread consumption and a higher RCC risk. A modest non-significant risk increase was also observed for pasta and rice. On the other hand an increasing intake of poultry, processed meat, and all vegetables, both raw and cooked, all reduced the risk of RCC.

These findings confirm our guess about insulin and/or insulin-like growth factors. This association between elevated cereal intake (bread, pasta and rice) is most likely due to the high glycemic index  of these foods, leading to an over-production of insulin and insulin-like growth factors.

The inverse relationship between vegetable consumption is consistent with previous studies and may be related to their content of vitamins, micronutrients or elements such as carotenoids, flavonoids and phytosterols.

This is not a perfect study: it is limited by the fact that the interviewers who gathered each participant’s information and administered the food questionnaire were not blind to who was who. But its big strengths include the sample size and the reproducibility and validity of diet information.

This study is important and speaks to the point that we have made before: a balanced diet is key, and your body does not want to be exposed to constant variations in glucose or insulin.

It also confirms all the advice that we have been offering you about what and when to eat. Click on the links to review what I have said before!

À Votre Santé!

I am a wine buff. Several years ago I did a one year training with the Wine and Spirit Education Trust which turned me from a dilettante to someone who knew how to understand the subtlety of wines from one end of a vineyard or another. Oh yes, and how to get very good wine for not many $$.

I also learned a whole range of other new skills. Ever since then I’ve been interested in the health consequences of drinking wine. Of course, too much of a good thing isn’t. But there has been so much evidence that certain types of wine, when used in moderation, can do wonderful things for your health.

This week has seen the publications of a paper in the journal Nature, that has been described by Steve Bloom from the Imperial College Faculty of Medicine like this: “It could be the breakthrough of the year, with massive possibilities for treating human beings.”

Steve is not given to hyerbole, so what has got him so passionate?

The answer is that a chemical found in dark grapes and in red wine called resveratrol, that could make guilt-free gluttony a reality.

Why is this?

Previous research has revealed the substance has anti-ageing effects in some organisms, extending the lifespan of yeast by 60%, worms and flies by 30%, and fish by about 60%.

It has also been suggested the reported health benefits of red wine may also be due to resveratrol.

When given to mice, it countered some effects of a high-calorie diet, with 60% of the calories coming from fat, improving their health and increasing their life-span. The mice showed decreased glucose levels, healthier hearts and liver tissue, and better motor function compared with the mice on the same diet but without the supplement.The chemical could not reverse all consequences of overeating – the mice did not lose any weight.

The researchers also discovered that the chemical was extending the mice’s life-span. The scientists estimated resveratrol reduced the risk of death in the mice by about 31%. After six months, resveratrol essentially prevented most of the negative effects of the high calorie diet in mice.

The exact mechanism of the chemical is not yet known, but the researchers believe it may be activating a gene called SIRT1, which is linked to a family of proteins thought to be involved with longevity.

This is not yet an invitation to enjoy limitless quatities of grapes or wine: a glass of red wine has only 0.3% of the relative resveratrol dose given to the gluttonous mice.


BTW, you may be interested to know that Nature is now providing an excellent podcast based on papers in this week’s edition.

Alexithymia

There is an important psychological symptom that can cause a great deal of distress, particularly in relationships. It is called alexithymia.

The Harvard psychiatrist Peter Sifneos originally coined the term in 1972 to describe people who had extreme difficulty in emotional cognition. The word “alexithymia” literally means “no words for mood.” People with this problem lacked the ability to understanding, processing or describing their feelings verbally. As a result, most people who have the problem are largely unaware of their own feelings or what they signify. As a result they only rarely talk about their emotions or their emotional preferences, and they are largely unable to use their feelings or imagination to focus and fuel their drives and motivations.

People with alexithymia seem unable to fantasize and many report multiple somatic symptoms. However, alexithymia is also associated with a number of other complaints, such as hypertension, irritable bowel syndrome, substance use disorders, and some anxiety disorders. Their speech is often concrete, mundane and closely tied to external events. So they will describe physical symptoms rather than emotions, and don’t understand that their bodily sensations are signals of emotional distress.

Alexithymia lies on spectrum: regular readers will remember some of our discussions about categorical and dimensional diagnoses. For some people it is little more than an inability to get in touch with their emotions. But at the other end of the spectrum are a number of illnesses in which alexithymia may occur, including schizoid personality disorder, posttraumatic stress disorder, anorexia nervosa or Asperger’s syndrome. It is also much more common in victims of trauma.

Much has been written about alexithymia: a literature search earlier today generated over 8,500 publications.

It is still not clear what causes alexithymia. But this much is clear: in some people, there is a strong inborn predisposition to developing it, while in others it can develop in response to life events such as being raised in a low socioeconomic group with little social stimulation, trauma or chronic stress. For this reason we often talk about primary and secondary alexithymia.

Some neuropsychological studies have indicated that alexithymia may be due to a disturbance to the right hemisphere of the brain, which usually plays a predominant role in processing emotions. Other studies show evidence that there may be a deficit in the transmission of information between the hemispheres of the brain, with emotional information from the right hemisphere not being properly transferred to the language regions in the left hemisphere. Other studies have suggested that alexithymia may be related to a dysfunction of the anterior cingulate cortex a region of the brain involved in the control of attention, empathy, emotion and the anticipation of rewards.

Alexithymia can have some serious consequences. Apart from making relationships very difficult, it is more common in people who have near-fatal asthma attacks or have poor diabetic control. People with a history of alcohol abuse who have alexithymia are more likely to relapse. Alexithymia may predispose people to developing the insulin resistance syndrome.

As you can see, alexithymia can be dangerous: we have to have words for our feelings, or the feelings will express themselves though our bodies. It can predispose us to just about every stress-related illness, and even some illnesses that we don’t normally think of as stress-related. Since alexithymia is all about an ability to express emotions, it can be thought of as a social or informational disease. If we cannot inform others about our wants and needs, and if our minds cannot send us signals to say that something is going wrong, there could be a catastrophe lying in wait for us.

People with extreme forms of alexithymia can be very difficult to help using conventional medicine.

However, many people have minor degrees of alexithymia, and these can be helped by therapies designed to help them express emotions:

  1. First is to become aware of the problem: I’ve had good success with asking people to keep an emotions “log book:” if they are having odd symptoms, how good are they about having appropriate emotions? I ask them to keep a note of their emotions in response to normal interactions with other people, or while watching television or a movie. If the person feels nothing while watching something really emotional, that can help him or her see that there is a problem. Simply learning to be more expressive can help mild cases: there are an array of forms of psychotherapy that can help.
  2. In mild cases, we have had some good results with flower essences. There’s not a shred of scientific proof that they help, but clinically they often do. The same goes for two other helpful approaches:
  3. Homeopathy: there are over a dozen remedies that may help
  4. Tapping therapies

Medicine and the Transformation of Illness

Something important has been happening in the medical field over the last century. And like most important concepts, once I mention it, everyone says, “Oh, that’s obvious.” Yet I have seen little discussion of it except in an occasional book or speculative paper.

The concept is this: modern medicine has been transforming the nature of illness in far-reaching ways. There are many illnesses that once were fatal, and which have now been transformed into chronic problems. Yet most conventional health care providers are still wedded to the short-term resolution of symptoms.

Let me give you three examples:

  1. The first is diabetes mellitus. There are two main types, and at least ten subtypes. Type 1 diabetes is what used to be known as juvenile onset diabetes or insulin-dependent diabetes. It usually comes on in childhood or adolescence, is associated with severe damage to the beta cells in the pancreas that produce insulin. People with this problem usually become very sick very quickly and need insulin to keep them alive. Until 1922, when the first patient was treated with insulin derived from cows, the illness was usually fatal. Insulin transformed it into a chronic illness. People were kept alive, but now we saw the emergence of diabetic eye disease (cataracts and retinopathy), disease of the blood vessels supplying the limbs, heart and kidneys, kidney failure, infections and many other chronic problems. In 1935 Sir Harold Himsworth, the father of a friend of mine, identified a second type of diabetes. He published a classic paper on his discovery of insulin resistance in 1936. This is what is now known as Type 2 diabetes, and used to be called maturity onset diabetes. This is a more chronic illness, but carries many of the same complications. The point about these two types of diabetes is not just that they have disturbances of glucose and lipid metabolism. That on its own matters little. It is the long-term consequences of the elevated glucose and lipids that causes all the problems.
  2. The second is hypertension. Again, this often used to be a fatal illness. Until the invention of the sphygmomanometer most people did not know that they had high blood pressure, and most often would die of strokes. Hypertension is now also a chronic illness. The problem is not the blood pressure itself, but the long-term consequences of an elevated blood pressure. That is why most physicians are now trying to prevent the damage to the heart, eyes and kidneys, instead of just focusing on the blood pressure numbers themselves.
  3. The third is Lyme disease. This is a bacterial illness that is acquired by being bitten by a tick. It is said to be the fastest growing infectious disease in the United States, primarily because we are spending more time venturing into the wilderness, and the deer population – a major carrier of the tick – is increasing in most Eastern states. Lyme disease can make people very ill. We identify acute and chronic types. The acute can usually be treated if identified quickly and if the correct treatment is given. But sometimes identification can be very difficult, and inadequate or even inappropriate treatment may lead to the chronic form. We have even seen people who have been treated exactly as the experts say, but have still developed the chronic form of Lyme disease. The biggest problem with Lyme disease is that it is a great masquerader: it can look like so many other illnesses, from multiple sclerosis and rheumatoid arthritis to chronic fatigue syndrome and syphilis.

We could pick out other examples. I have mentioned some of the problems of thinking that attention deficit disorder is just a problem with getting good grades in school. When in reality the problem is that inadequately treated ADD is associated with a range of long-term problems that occur outside of school hours.

For many years now some practitioners have been warning about the long-term consequences of symptomatic treatment alone. One of the most eloquent critics of this way of treating people is the Greek homeopath and teacher George Vithoulkas. I like and respect George, but he takes a militant view, saying that conventional treatment simply suppresses illnesses, rather than treating them. His solution is to use homeopathy for everything. He is a genius and also a natural healer, so he can probably get away with that. Most of us cannot.

So the fundamental tenets of Integrated Medicine include medical treatment to deal with the acute problem, but a combination of approaches to prevent the problem from becoming chronic. Or if it has become chronic, then how to change its course over time.

As I’ve said before: Combinations are Key. Not randomly giving an antibiotic as well as a homepoathic remedy, but precisely tailoring the combination to the individual.

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