Richard G. Petty, MD

A New Approach to the Diagnosis and Treatment of Depression

Although textbooks and pharmaceutical company literature often claim that the biological component of depression has been clearly defined, the fact is that we still have no certain knowledge about the molecular and biochemical disturbances in depressive disorders. Furthermore, our theories of how antidepressants are constantly being revised, and it is now thought likely that these drugs have several mechanisms of action.

There is an interesting study from the University of Illinois at Chicago College of Medicine and Maryland Psychiatric Research Center in Baltimore in today’s issue of the Journal of Neuroscience.

They have discovered that a change in the location of a protein in the brain could serve as a biomarker for depression. This is exceptionally important, since it may give us a simple and rapid laboratory test to identify patients with depression and, more importantly, to predict clinical response to specific antidepressants.

Over the last few years this same team of researchers, and others around the globe, have been examining a protein named Gs alpha that activates adenylyl cyclase. Adenylyl cyclase is a link in signal transduction that is in part responsible for the action of neurotransmitters including serotonin. Instead of just looking at the biochemical properties of the protein, they have also been looking at the way that it moves in the cell membrane, which in turn impacts the way in which neurotransmitters act on cells.

In both rats and cultured brain cells, Gs alpha changes its location in response to antidepressants, moving out of lipid “rafts” in the cell membrane, to areas of the membrane that allow more efficient communication among membrane components responsible for the action of neurotransmitters. Both antidepressant and antipsychotic drugs have been shown to concentrate in these lipid rafts.

In this new study, brain samples from depressed people who had committed suicide were compared with controls who had no history of psychiatric disorders. Although the total amount of Gs alpha was the same in the depressed and non-depressed, in people with depression, Gs alpha was stuck in these lipid “rafts.” Therefore the protein is unable to do its job of mediating the action of neurotransmitters. Antidepressants have the opposite effect, moving it to regions of the membrane where it can do its work. The localization of other G proteins was not different.

This is such a robust finding, that identifying the location of Gs alpha in the cell membrane may provide an objective diagnosis of depression and second, whether someone is responding to the chosen antidepressant therapy.

The senior author in this research is Mark Rasenick, who is distinguished university professor of physiology and biophysics and psychiatry at the University of Illinois. He described the lipid “rafts” and the importance of the findings like this:

"These “rafts” are thick, viscous, almost gluey areas, that either facilitate or impede communication between membrane molecules… When Gs alpha is caught in these lipid raft domains, its ability to couple with and activate adenylyl cyclase is markedly reduced. Antidepressants help to move the Gs alpha out of these rafts and facilitate the action of certain neurotransmitters."

He goes on to say,

"This test could serve to predict the efficacy of antidepressant therapy quickly, within four to five days, sparing patients the agony of waiting a month or more to find out if they are on the correct therapeutic regimen."

The findings may also help explain two old puzzles:

• Why do antidepressants take so long to work?
• Why do such chemically different compounds produce similar clinical effects?

Further studies to confirm and expand these findings, and to examine the clinical utility of the test.

Are Antidepressants Effective?

An important story has been flashed around the world, but unfortunately some of the interpretations of the story have been intemperate. In a study published in PLOS Medicine a  team of researchers from the University of Hull team concluded the drugs actively help only a small group of the most severely depressed. They based this on a meta-analysis of all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available.

The researchers reviewed data on 47 clinical trials, both published clinical trial data, and unpublished data secured under Freedom of Information legislation.

They focused on four antidepressants: fluoxetine (Prozac), venlafaxine (Effexor), nefazodone (Serzone) and paroxetine (Paxil).

Many of the reports in the media have taken this research to mean that antidepressants are no better than placebo. That is not the case. The medications can be very effective and even life saving in people with severe depression. However, the effect in people with mild depression is no greater than placebo.

What this tells us is that the over-prescription of antidepressants for normal variations in mood is probably not justified. We are all allowed to be miserable from time to time, but that does not mean that we need to take medications.

Not surprisingly, some of the manufacturers have strongly disputed the findings.

The biggest worry after reading some of the news reports is that some people might stop their medications abruptly, and that can cause many problems. And some folk really do need to be on the medications and stopping them without clear guidance can be very risky.

Mold, Dampness and Depression

It matters where you live.

I have lived or stayed in many countries, and there is no doubt that some places are a lot more congenial than others. I don’t just mean a beach in Thailand compared with the North of Scotland in winter. Some places just make you feel better. There are many physical, psychological, social and subtle reasons, but here is a relatively new one.

There is an important paper in this month’s issue of the American Journal of Public Health looking at the possibility of a link between dampness and mold in the home and clinical depression.

Molds are fungi that are found in many environments but most of them grow best in warm, damp, and humid conditions. Therefore, dwellings that have problems with damp also commonly have problems with mold. Although the physical health consequences of living in a damp and moldy dwelling are quite well known, the effect of living in such an environment on mental health has not.

Some of the known health problems associated with high levels of airborne mold spores include^:

• Allergic reactions
• Asthma
• Irritations of the eyes, nose and throat
• Sinus congestion and other respiratory problems
• In people with with weakened immune systems, inhaled mold spores may germinate, attaching to cells along the respiratory tract
• Immunocompromised individuals exposed to high levels of mold may get a systemic fungal infection
• Infections of the digestive tract, lung and skin

The researchers used survey data from 8 European cities. They created a dampness and mold score from resident- and inspector-reported data. Depression was assessed using a validated index of depressive symptoms.

The results showed that dampness and mold were associated with depression, independent of individual and housing characteristics. This association was independently mediated by perception of control over one's home and by physical health.

This link is most likely because of the psychological and physiological consequences of living in poor housing conditions. But there could also be a direct pathological effect of mold itself.

Optimism and the Brain

Humans have a wonderful ability to expect positive events in the future, even when there is no shred of evidence to support them. One of the key components of resilience is optimism. Though there is data to show that there is a genetic contribution to optimism, it is also a psychological attribute that can flow from life experiences as well as attitude that can be developed. Though the motivational coaches who tell us that putting on a happy face will make you happy and optimistic are probably overstating the truth! A lack of optimism is often a sign of clinical depression so learning more about it, is not just an academic exercise.

New research just published in the journal Nature indicates that there are two regions of the brain linked to optimism.

The team from New York University and University College, London, says that the act of imagining a positive future event, for example winning an award or receiving a large sum of money, activates two brain areas: the amygdala and the rostral anterior cingulated cortex (rACC). The finding ties in with earlier studies that suggested that these brain regions malfunction in depression. (1,2)

The investigators first measured how optimistic 15 volunteers were using a standard questionnaire. They were then scanned using functional magnetic resonance imaging (fMRI) while reflecting on one of a number of potential scenarios.

In one part of the trial, subjects followed specific instructions to recall a negative event in the past, such a funeral that they had attended in the past five years. In another experiment they had to imagine what it would be like to be involved in a car crash in the near future. At other points in the study subjects had to reflect on positive events such as winning an award in the past or receiving a large sum of money in the future.

Reflecting on both past and future events activated the amygdala and the rACC regions of the brain. However, positive events, and particularly those imagined in the future, generated a significantly larger response in these regions than reflecting on negative events.

When imagining happy events, the more pessimistic subjects in the trial had less activation of these brain areas than their optimistic counterparts when imagining happy events.

For some time now, many researchers have assumed that the amygdala and rACC are only involved in negative thoughts and negative reactions, but this research indicates that they have an important role in signaling cheerful thoughts. And, what is more, these are also regions of the brain that have been implicated in depression. Previous research has suggested that patients with depression have decreased nerve signaling and fewer cells in the rACC and amygdala.

Is this why people with depression find it so hard to generate positive thoughts?

This is important work that will likely have a great many practical applications.

“Children are born optimists and we slowly educate them out of their heresy.”
--Louise Imogen Guiney (American-born English Poet, 1861-1920)

“Although the world is full of suffering, it is full also of the overcoming of it.”
--Helen Keller (American Blind and Deaf Swedenborgian Philosopher, 1880-1968)

“No man is so old as not to think he can live one year more.”
--Marcus Tullius Cicero (Roman Political Figure and Orator, c.106-43 B.C.E.)

"The way to become happy
Is to think

And to feel

That the very best is yet to come.”
--Sri Chinmoy (a.k.a. Chinmoy Kumar Ghose, Indian Philosopher and Spiritual Teacher, 1931-2007)

Sleep Deprivation and Emotional Instability

Most of the time we are in control of our moods, rather than our moods being in control of us. One of the main things that we learn as we get older is not simply to damp down our emotional reactions, but to make them “contextually relevant:” we produce the right emotional response for the right situation. Yet we also know that there are exceptions: times when our emotions over-run any attempts at our control.

Second, we all know that sleep deprivation can be a Bad Thing. It is known to impair a range of mental and physical activities, including immune function, metabolic control and many cognitive processes, including learning and memory.

It has long been suspected that sleep deprivation can have significant effect on mood. Many of us feel irritable and distractible if we haven’t slept enough, and you may have had the experience of being up all night and feeling a little bit “high” in the morning. It has also been known for centuries that mood disorders are very commonly associated with sleep disturbances, and sleep disturbance is often the first sign that someone with mood problems is running into trouble. So mood and sleep must be linked in some way.

Despite these common observations, there has never been that much empirical evidence for the impact of sleep deprivation on mood, and in particular the effects of sleep deprivation on the brain.

An important new study by researchers from Harvard Medical School and the University of California at Berkeley has just been published in the journal Current Biology, and it is beginning to fill in some of the gaps in our knowledge.

The amygdala is known to be involved in processing of emotionally salient information, particularly unpleasant or aversive stimuli. In mature individuals, the emotional centers of the brain are usually controlled and modulated by an array of connected systems, mainly in the frontal regions of the brain. One particularly important part of the frontal lobes that is involved in controlling the amygdala is the medial-prefrontal cortex (MPFC). Under normal conditions the MPFC is supposed to exert an inhibitory, top-down control of the amygdala, so that we only generate appropriate emotional responses.

The scientists worked with 35 volunteers who were deprived of sleep for 35 hours. Blood flow can be used to deduce which specific regions of the brain are active. The researchers used functional magnetic resonance imaging (fMRI) to examine the blood flow – and therefore activity - in the brains of the volunteers in real time, both during and after sleep deprivation.

After going without sleep, the participants were asked to look at images that were designed to trigger angry or sad emotional responses. The investigators discovered that the amygdala showed 60% higher reactions to the images compared with people who are not sleep-deprived.

This is an extraordinarily large effect and implies that sleep deprivation knocks out the normal control mechanisms in the frontal lobes so that the sleep-deprived brain reverts to a more primitive pattern of activity. As a result we become unable to put emotional experiences into context and produce controlled, appropriate responses.

If we needed any more reasons to get a good night’s sleep, this one is very powerful. It also re-iterates something very important: if you or a loved one have had problems with mood, anger or anxiety, it is essential to watch your sleep pattern. Any change may be a harbinger or trouble, and is an excellent early warning that you or they need a hand to make sure that things stay on an even keel.

"Your brain shall be your servant instead of your master, you will rule it instead of allowing it to rule you.”
--Charles E. Popplestone (American Author of Every Man a Winner, 1936)

“Control your emotions or they will control you”
--Chinese Proverb

“For the uncontrolled there is no wisdom, nor for the uncontrolled is there the power of concentration; and for him without concentration there is no peace. And for the unpeaceful, how can there be happiness?”
--Bhagavad Gita (Ancient and Sacred Sanskrit Poem Incorporated into the Mahabharata)

“He who controls others may be powerful, but he who has mastered himself is mightier still.”
--Lao Tzu (Obscure Chinese Philosopher, Founder of Taoism and Alleged Author of the Tao-Te Ching, c. 604-c. 531 B.C.E.)

“ . . . let every man be swift to hear, slow to speak, slow to wrath.”
--The Bible, James 1:19

“When angry, count ten before you speak; if very angry, a hundred.”
--Thomas Jefferson (American Writer, Philosopher, Politician and, from 1801-1809, 3rd President of the United States, 1743-1826)

Chocolate, Comfort Foods and Depression

Most people have done a bit of comfort eating from time to time: candies and chocolates are usually the favorites. That’s not a coincidence. Not only do they taste good, but chocolate also contains chemicals that may improve mood, and sugar can have an indirect impact on the uptake of specific amino acids into the brain, where they go on to form the chemical neurotransmitters involved in inter-cellular communication and learning.

On the more serious side, some types of mood disorders, particularly seasonal affective disorder, premenstrual syndrome and the so-called “atypical depression” are often associated with quite sever cravings for chocolate.

So I was very interested to see a paper from colleagues in Australia in this month’s issue of the British Journal of Psychiatry.

Gordon Parker and Joanna Crawford examined links between chocolate craving in people who are depressed and both personality style and atypical depressive symptoms, with a web-based questionnaire completed by nearly 3000 individuals reporting clinical depression.

People accessing a mood disorder consumer information website (http://www.blackdoginstitute.org.au) were invited to participate in an online survey of lifetime treatments for a depressive episode, together with some interesting evaluation tools.

Half of the respondents said that they craved chocolate, and the number was slightly higher in women. They said that they felt that chocolate helped with depression, anxiety and irritability. The ones who said that chocolate helped were more likely to score higher on a “neuroticism” scale, particularly irritability and rejection sensitivity.

Five years ago the same team found that atypical depression was associated with a personality that was especially sensitive to rejection, and also tended to be linked with several symptoms - including food cravings – that tie in with behaviors aimed to try and make us feel better and to maintain internal balance.

The results suggest that people with certain personality styles derive personal benefit from comfort eating. Some research has linked carbohydrate craving to the opioid system in the brain, and it is possible that munching on chocolate may be an example of genuine self-medication. People eat to chocolate to calm down their ability to feel emotional distress.

The trouble is, of course, that although chocolate is yummy and may even be therapeutic, too much can be a bad thing. Weight problems are common in people with chronic depression, especially the “atypical” type.



“Chocolate causes certain endocrine glands to secrete hormones that affect your feelings and behavior by making you happy. Therefore, it counteracts depression, in turn reducing the stress of depression. Your stress-free life helps you maintain a youthful disposition, both physically and mentally. So, eat lots of chocolate!”
--Elaine Sherman (American Culinary Expert, Teacher and Writer, 1938-2001)

"Look, there’s no metaphysics on earth like chocolates.”
--Fernando Pessoa (Portuguese Poet, 1888-1935)

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

Sleep and Your Heart

The amount of sleep a person gets affects his or her physical health, emotional well-being, mental abilities, productivity and performance. Recent studies associate lack of sleep with serious health problems such as an increased risk of depression, obesity, cardiovascular disease and diabetes.

There was some interesting research presented at SLEEP 2007, the 21st Annual Meeting of the Associated Professional Sleep Societies in Minneapolis in the middle of June.

One study that caught my eye was conducted by Siobhan Banks of the University of Pennsylvania School of Medicine. The research was based on preliminary analysis of 39 subjects, each of whom participated in a laboratory-controlled chronic sleep restriction protocol. The subjects underwent two nights of baseline sleep followed by five hours of sleep restriction. The results showed a statistically significant decrease in the heart rate variability after just five nights of sleep restriction.

We already know that a reduction in heart rate variability may occur in several cardiological and non-cardiological diseases, and it is usually a harbinger of a poor outcome.

This work may provide the mechanism for why short sleep duration is associated with a heightened risk of heart and other circulatory problems.

The amount of sleep a person gets affects his or her physical health, emotional well-being, mental abilities, productivity and performance. Recent studies associate lack of sleep with serious health problems such as an increased risk of depression, obesity, cardiovascular disease and diabetes.

So if confirmed, the take home message is that sleep deprivation has a negative effect on a person's cardiac activity and that may in turn increase the risk of cardiovascular disease and mortality.

Emotions and Recovery from Hip Surgery

A patient's emotional state plays a significant role in his or her recovery from hip surgery according to research from Saint Louis University. This research was particularly interesting because the researchers were not looking for a link.

Orthopedic surgeons typically use two tests to determine if a patient has recovered from hip surgery: one is a clinical measure of hip function and the second is a patient questionnaire that looks at a number of factors that may play a role in the overall success of the surgical procedure. Originally the research was simply designed to see if the two measures, the clinical one that has been in use for decades, the other, a new subjective scale, correlated in some way.

The clinical test found good-to-excellent results, while the self-test taken by the same patients showed significantly worse recovery. The disparity could be explained by a section of questions on the self-test that are not addressed by the clinical test: those dealing with emotional well-being. After post-operative mobility, the patient's emotional status was the most important factor in determining how well he or she thought recovery was going.

It is common for doctors to think that patients are doing well because they have achieved a good technical result. But if the patient is still miserable, depressed and in pain, we should not congratulate ourselves on a job well done.

Yet a great many people are denied the help that they need. For instance they may have already had depression or they may be depressed because of pain and immobility. It does not really matter which came first. If the psychological aspects of the illness or the surgery are not addressed, people are not likely to recover. The same goes for having poor nutrition or poor social supports.

The whole point of Integrated Medicine is to address every aspect of a person: physical, psychological, social, subtle and spiritual.

This study provides further evidence that if we only look at the physical aspects of a problem or an intervention, we are going to miss the boat.

Mindfulness and Depression

 

Mindfulness meditation has rightly been receiving a lot of attention recently. It is quite simply a technique in which you become intentionally aware of your thoughts and actions in the present moment, non-judgmentally. Though originally a Buddhist technique, it is something that can be practiced by anyone, and there are, in fact, similar techniques that have been developed by Christian mystics and Sufis.

It has recently been discovered that some of the techniques that were developed so that a mystic or meditator could carry on without distraction, may also have value in treating clinical problems. After all, if a group of people has spent a thousand years developing tools and techniques for managing the mind, it might be a good idea to see what they have discovered!

There have recently been several excellent books on the use of mindfulness in the management of depression:
The Mindful Way Through Depression 
Relaxation, Meditation and Mindfulness
Mindfulness and Acceptance: Expanding the Cognitive-Behavioral Tradition

This whole field was moved forward by some research from San Francisco (NR822) that was presented at the end of May at the 2007 Annual Meeting of the American Psychiatric Association in San Diego. The researchers used Mindfulness-Based Cognitive Therapy (MBCT) in a group of 53 people with treatment resistant depression.

MBCT is based on the Mindfulness-based Stress Reduction (MBSR) eight-week program that was developed by Jon Kabat-Zinn in 1979 at the University of Massachusetts Medical Center. Research has show that MBSR can be enormously empowering for people with chronic pain, hypertension, heart disease, cancer, and gastrointestinal disorders, as well as for psychological problems such as anxiety and panic.

Mindfulness-based Cognitive Therapy grew from this work. Zindel Segal, Mark Williams and John Teasdale adapted the MBSR program so that it could be used for people who had suffered repeated episodes of depression.

The results of the study presented in San Diego showed that MBCT was effective in reducing depression when compared to treatment as usual: what we call “TAU.” What seems to happen is that MBCT gives people a set of skills for detaching from the stream of depressive thoughts and feelings. As a result the symptoms decrease. Though the study will need to be expanded and replicated, this is clearly a fertile area for research.

This work is also interesting in the light of recent research showing that mindfulness training may improve the activity of some of the subsystems of the brain dedicated to attention, as well as helping  some people with mental illness control their aggressive behavior. Mindfulness training may also help to reduce subjective reduces distress and improves positive mood states. It seems to be particularly good at reducing distracting and ruminative thoughts and behaviors.

And just for good measure, mindfulness may help some smokers quit.

“The purpose of meditation is not enlightenment, it is to pay attention even at extraordinary times, to be of the present, nothing-but-in-the-present, to bear this mindfulness of now into each event of ordinary life.”
--Peter Matthiessen (American Naturalist and Writer, 1927-)

“Meditation is not to escape from society, but to come 
back to ourselves and see what is going on. Once there is 
seeing, there must be acting. With mindfulness, we know 
what to do and what not to do to help.”
-- Thich Nhat Hanh Vietnamese Buddhist Monk, 1926-)

“Conscious means "having an awareness of one's inner and outer worlds; mentally perceptive, awake, mindful." So "conscious business" might mean, engaging in an occupation, work, or trade in a mindful, awake fashion. This implies, of course, that many people do not do so. In my experience, that is often the case. So I would definitely be in favor of conscious business; or conscious anything, for that matter.”
--Ken Wilber (American Philosopher, 1949-)

Spirituality, Depression and Suicide

It is an interesting sign of the times that a major medical publication - the Southern Medical Journal - has dedicated an entire section this month to a series of papers on the Spirituality/Medicine Interface Project that is being supported by the John Templeton Foundation.

Attention to our spirituality is an important part of fulfilling our potential and treating people in trouble. It is no accident that Integrated Medicine always includes all of the five major dimensions of an individual:

• Physical
• Psychological
• Social
• Subtle
• Spiritual

To get a bit technical, each of the five domains or dimensions contains something of each of the others. The body, mind and spirit and not separate but part of one whole. Mind, consciousness and spirit permeate the body.

We sometimes use the technical term “Five Interlinked Nested Domains” or “FINDS,” to reflect this reality.

An important principle of this interconnected health model is that it’s almost always a mistake to look for a single cause for a problem, imbalance or illness. Not only is it usually incorrect to think about “one illness, one cause,” but it is also usually not enough to use just one therapy or one health maintenance plan: Carefully coordinated combinations are key, for they generate a powerful synergy.

Because the domains are interlinked, physical and psychological health, to say nothing of our social health, and the health of our subtle systems are difficult to maintain without spiritual health. The road to spiritual health begins with understanding and following the natural laws of the Universe, finding your true Purpose and applying both to the service of others.

The articles in this issue of the Southern Medical Journal are excellent.

Here are some highlights:
Dan Blazer from Duke University provides an introduction that gives a fine overview of the growing field of spirituality in medicine in general and depression in particular
Harold Koenig, also from Duke has an article entitled, "Spirituality and Depression: A Look at the Evidence"
Bob Cloninger from Washington University in St. Louis writes about "Spirituality and the Science of Feeling Good."

Unfortunately the abstracts and papers are not yet available on line, except to members of the Southern Medical Association. Hopefully the Templeton Foundation will be able to arrange with the Journal to make at least the abstracts freely available.

If they do, I shall let you know.

Otherwise, if you have ready access to a library, and if you are interested in this important and rapidly growing field, I am sure that they will be able to help you.

Solar Cycles and Human Disease

We have all heard about the supposed association between full moon and mental illness, though most of the research has failed to find an association between phases of the moon and mood disorders or psychosis.

But something that we have not heard so much about is the possible association between solar activity and human problems.

Investigators from Chile presented some interesting data (NR308) at the 2007 Annual Meeting of the American Psychiatric Association in San Diego last month.

They used a measure of solar activity called the Wolf number that is based on the number of sunspots. The sunspot cycles are usually between 9.5 and 11 years. They examined the clinical records of 1862 individuals who had been seen at a psychiatric clinic in Santiago over a sixteen-year period, which corresponded to one and a half solar cycles. They found that there was a big rise in admission for severe depression during years with low solar activity and a slight increase in the number of admission for mania during years of high solar activity.

This is not the first time that a connection has been found between the sun and human affairs.

The same authors published a paper in Spanish two years ago in which they also found that depression is more common when there is less solar activity and mania increases when there is more activity. They cannot say whether it is just light that is causing this or some other form of radiation.

Two researchers used the Maine Medicaid database to look at the relationship between solar cycles and human disease, and found that that radiation peaks in solar cycles and particularly in chaotic solar cycles (CSCs) are associated with a higher incidence of mental disorders. The same researchers had previously used the same database to suggest that CSCs produce more ultraviolet radiation and it is this that limits human longevity by causing chromosomal damage.

Interestingly, in 1993 two researchers also suggested a relationship between solar activity and longevity. They looked at the mean longevity of birth cohorts from 1740 to 1900 for United States of America (U.S.) Congressional Representatives exhibited oscillations that coincided with the 9- to 12-year sunspot cycle. They found that the mean longevities of these cohorts were 2-3 years longer during times of low sunspot activity than at peak activity. This phenomenon was confirmed in data from members of the House of Commons of the United Kingdom Parliament and from University of Cambridge alumni.

Researchers in Slovakia have suggested that there may be an association between solar radiation and cerebral strokes, though their data is a little difficult to interpret.

It is clear that the Heavens have more of an impact upon us than many scientists realized, and need to be factored into studies of human mood and behavior.

Larks, Owls and Depression

It is well known that mood disorders are associated with the disruption of many of the circadian rhythms of the body including sleep, temperature and thyroid function. These links are so well known that many experts believe that depression may be a consequence of disturbances in circadian rhythms.

Although circadian rhythms tend to be fairly consistent across individuals, but there are significant differences in these rhythms in different people: we call this the "morningness-eveningness” dimension (MED).

As part of a larger project, researchers from Providence, Rhode Island last month presented a most interesting study (NR293) at the 2007 Annual Meeting of the American Psychiatric Association in San Diego.

People with psychiatric problems tend to be owls: evening types who don't like mornings, and this was particularly striking in people with depression.

This suggests that “eveningness” may be reflecting a risk factor or vulnerability to psychopathology, in particular depression. It may actually be that if you are a “morning person,” you may have some protection against developing depression.

I remember seeing a study from Stanford in April that suggested that people labeled a “night owls” report more pathological symptoms related to insomnia, despite many having the opportunity to compensate for their nocturnal sleeplessness by extending their time in bed and being able to gain more total sleep time. So this may be the link with depression.

Yoga and the Brain

Depression and anxiety are increasingly common throughout the world, and although each may be a consequence of psychological and environmental stresses, there is also a genetic predisposition and an increasing number of reproducible disturbances in the brain.

In recent years, there has been increasing interest in the role of brain gamma-aminobutyric acid (GABA) levels, which is the brain's primary inhibitory neurotransmitter, in both depression and anxiety, following the finding that each may be associated with low levels of GABA in different regions of the brain.

There have also been reports that yoga may help stress and anxiety as well as depression.

Now colleagues from Boston University School of Medicine (BUSM) and McLean Hospital have found that practicing hatha yoga may elevate brain GABA levels.

This new research is published in last month’s issue of Journal of Alternative and Complementary Medicine.

The researchers used magnetic resonance spectroscopic imaging to compare the GABA levels of eight subjects before and after one hour of yoga. The control group consisted of 11 people who read a book or magazine instead of doing yoga. They found a twenty-seven percent increase in GABA levels in the yoga practitioner group after their session, but no change in the comparison subject group after an hour spent reading.

It is too early to start recommending yoga for the treatment of depression or anxiety, but it is fascinating that it will produce changes in brain chemistry that are very similar to those that we hope to achieve with other forms of therapy.

Humor and the Treatment of Depression

There is a well-known story about the writer Norman Cousins who claimed to have beaten ankylosing spondylitis by watching Laurel and Hardy and Marx Brothers movies. In his book Anatomy of an Illness as Perceived by the Patient, he chronicles the way in which he laughed his way to health.

In recent years there has been a great deal of interest in the idea of using laughter to prevent and treat mood disorders. We have Laughter Clubs and even Laughter Yoga.

When you first hear about it, the whole idea sounds preposterous: if you are suffering from clinical depression, it is not very likely that you are going to feel like laughing. 

So it was very interesting to see some new research (NR46) from colleagues at Cedars-Sinai Medical Center that were presented yesterday at the 2007 Annual Meeting of the American Psychiatric Association in San Diego, California.

Some literature has suggested that humor may help reduce stress and anxiety, but the data has been inconclusive.

The researchers investigated the dispositions toward humor of a group of depressed patients in the outpatient psychiatric department at Cedars-Sinai. Patients were asked to complete a short questionnaire comprised of a regular depression scale as well as Svebak’s Sense-of-Humor Questionnaire.

The researchers had predicted that the level of depression and inherent sense of humor of an individual would determine whether or not they thought that humor would be a viable component of treatment.

In fact there was no correlation with either: depressed people were remarkably receptive to the idea of including humor in their treatment. The researchers are now planning some controlled studies of incorporating humor into the treatment of depressed patients.

Perhaps Patch Adams was right all along!

Non-pharmacological and Lifestyle Approaches to Attention-Deficit/Hyperactivity Disorder: 3. Herbal Remedies

Herbal medicines are crude drugs of vegetable or plant origin, which are used for the prevention or the treatment of disease states or to attain or maintain a condition of improved health. The use of herbs can be divided into four main categories:

1. Folk Herbalism: You may well have come into contact with this: we use the term folk herbalism to describe traditional healing methods based upon plants. Many of our ancestors brought folk remedies from Europe or learned of healing herbs from Native Americans
2. Western Medical Herbalism: This has been developing in Europe over the last century, and represents an attempt to classify and codify medically useful herbs
3. Ayurvedic Herbalism: This is the ancient traditional herbalism of the Indian Subcontinent. Some Ayurvedic herbs have found their way into conventional medicine. The best-known example is the drug reserpine, which was at one time used for treating high blood pressure and mania. It was extracted from the Himalayan bush Rauwolfia serpentina. Ayurvedic herbs are most readily available in cities with large Indian populations
4. Chinese Herbalism: One of the five branches of traditional Chinese medicine, there are many thousands of Chinese herbs, which are usually administered in complex combinations. Though most are prepared with close attention to detail, there have been many reports in the literature of adulteration of Chinese herbs with heavy metals.

Herbs are used directly as teas or extracts, or they may be used in the production of drugs. Around 25% of the prescription drugs sold in the United States are plant based. Two good examples are aspirin, which was originally extracted from the bark of the willow tree and digoxin, a purified form of digitalis, from the foxglove. Many more herbal ingredients are present in over-the-counter medicines, particularly in laxatives.

Herbal medicines are considered to be dietary supplements; therefore they are not required to meet the standard for drugs specified in Federal Food, Drug, and Cosmetic Acts. They are only required to meet the standards set forth in the 1994 Dietary Supplement and Health Education Act (DSHEA). Furthermore, they may be produced without complying with standards for good manufacturing practice. They also do not need the prior approval of safety and efficacy by the Food and Drug Administration (FDA). So long as the term “disease” is not on the label, the FDA has no regulatory powers.

Many herbal products have been used to treat Attention-Deficit/Hyperactivity Disorder (ADHD), and there are hundreds of websites claiming that their products are effective. However the research is often not quite what it seems. Some sites simply use loads of testimonials, but happily there are others who have products supported by empirical research. The use of herbal remedies in ADHD is popular in Europe, although the problem is less widely recognized in that part of the world. The most popular include sedative herbs, herbs used to enhance brain function, antioxidants and stimulants. The last category is herbs that are used to treat other symptoms, particularly mood disorders that are very common in adults with ADHD.

Medical reviews of herbal remedies do not always make the point that herbalists typically individualize the treatment for the individual. So two people with apparently similar symptoms may receive different treatments.

They are often used together with a whole-foods diet, high in protein and complex carbohydrates and low in simple sugars.

Sedative herbs
Sedative or calming herbs are amongst the most popular herbal options for treating ADHD. These include:
Chamomile
Hops
Lemon balm
Valerian
Kava kava

Sedative herbs may be helpful in promoting sleep in children who have trouble falling asleep. They are generally safe, but there is little scientific evidence that they can improve daytime behavior in children with ADHD, and it is important to be aware that they are medicines that do have side effects and may interact with each other and with prescription medicines. Here is a chart of some interactions between medicinal herbs and drugs.

Brain "enhancing" herbs
A small open study of 36 children with ADHD who were treated with a combination herbal combination of Panax quinquefolium (200 mg) + Ginkgo biloba (50 mg) twice daily for 4 weeks, reported an improvement in 74% at the end of the study. The combination was marketed as AD-FX, but it has recently become difficult to obtain it in the United States for commercial rather than legal reason. Gingko has become one of the most popular herbs given to children with ADHD, but more research is necessary: there is enormous variability in the quality of commercially available herbs. Gingko may also cause bleeding in people at risk of it. It was interesting that Panax was included: there are reorts of people becoming more hyperactive in overdose. 


Antioxidant herbs
Pycnogenol (pine bark extract) has been tested in a randomized, controlled trial involving 61 children who received either 1 mg/kg/day Pycnogenol or placebo for 4 weeks. In this study, Pycnogenol was associated with a significant reduction of hyperactivity, improved attention, eye-hand coordination, and concentration. When the herb was stopped, the symptoms returned within a month.  An earlier short study in adults had failed to find an effect, but it could have been because of the dose used.

Stimulant herbs
Coffee, tea, and cocoa all have stimulant effects that tend to be milder than medications. Caffeine helped spatial learning deficits in an animal model of ADHD, and there have been several small studies of caffeine, but most have failed to find much benefit. In a double-blind cross-over trial  of just 8 boys with ADHD modest doses of caffeine (160 mg, roughly equivalent to 1.5 cups of coffee) were less effective than large doses of methylphenidate (20 mg) in improving behavior. Although many adults self-medicate with coffee, few use it in children with ADHD. And it can, of course, cause insomnia and anxiety.

Chinese herbalists use multiple combinations and there have been some publications (1, 2, 3,) suggesting that further work on Chinese herbal medicines might be worthwhile. The methods of some Chinese medical research studies are rather different from those done in the West, so we need to be a little cautious.
   
There are some herbs and supplements that are linked to an increase in symptoms of hyperactivity including:
Yohimbine
Korean ginseng
Siberian ginseng
American ginseng
L-glutamine

Conclusions
Although there is some data, and a lot of practical experience, it is still not clear who is likely to benefit from which herbal remedy. The variable quality of herbal products and the risk that some may be contaminated has added to the uncertainty. It is also important to remember that herbs are drugs, and that they can interact with each other and with prescription medicines, and that just because they are natural, does not necessarily mean that they are safe.

After all, deadly nightshade, arsenic and hurricanes are natural as well.

An Important Change in the Warning on Antidepressant Medicines

If we could, we would only use natural medicines to treat depression.

Sadly it is not always possible to do that, and it doesn't help when people with a demonstrable biochemical disturbance are told that their depression is all about internalized anger or an unwillingness to face some issue in their lives.

The trouble with those theories is that they often don't take into account a tragic fact: depression can be fatal.

Not only because of the risk of suicide and other kinds of self-injury, but because depression is associated with many physical problems including chronic inflammation and carbohydrate intolerance.

Today the United States Food and Drug Administration (FDA) asked makers of all antidepressant drugs to change the existing "black box" labels on their products to warn about increased risk of suicidality (suicidal thinking and behavior) among young adults aged 18 to 24 in the first few weeks of treatment.

The FDA has also asked the pharmaceutical companies to revise the existing warning to show that there is no evidence that this risk exists for adults over 24, and furthermore, for those aged 65 and older the scientific data suggests the suicidality risk is decreased.

The American Psychiatric Association (APA) said this:

"The FDA's new labeling acknowledges, for the first time, that untreated depression puts people at risk for suicide."

They said that studies showed that the old label issued in 2004 was associated with a steep drop in use of antidepressants and was followed by an increase in the rate of suicide "reversing a decade-long decline in suicide deaths in the United States".

The FDA said the emphasis on the new labels should be that depression and other serious psychiatric illnesses are themselves the most important causes of suicide.

Director of FDA's Center for Drug Evaluation and Research, Dr Steven Galson said that:

"Today's actions represent FDA's commitment to a high level of post-marketing evaluation of drug products."

"Depression and other psychiatric disorders can have significant consequences if not appropriately treated. Antidepressant medications benefit many patients, but it is important that doctors and patients are aware of the risks."

The FDA recommends that people who are currently taking antidepressants should not stop taking them as a result of hearing this news.

The warning revision applies to all antidepressants and comes in the wake of controlled trials that showed a reasonably consistent risk of suicidality across most of the antidepressant drug categories. The FDA said that the evidence does not support excluding any antidepressant medication from this update request.

This update request follows the labeling changes made in 2005 to warn of increased suicidality in children and adolescents taking antidepressants.

Since then, the FDA undertook a comprehensive review of 295 drug trials examining the risk of suicidality among adults taking antidepressants.

The trials included over 77,000 adult patients with major depressive disorder (MDD) and other psychiatric conditions.

The results was that in December last year, the FDA's Psychopharmacologic Drugs Advisory Committee said labels should be changed to tell doctors about the increased risk of suicidality among younger adults taking antidepressants.

The Committee also said the labels should remind doctors that the disorders themselves present the greater risk, and that among older adults the antidepressants do not carry the suicidality risk and have an apparent beneficial effect.

The FDA is preparing drafts of patient guides and wording for the labels. The manufacturers have 30 days to submit their own versions for FDA review.

The drugs affected include:

-- Anafranil (clomipramine)
-- Asendin (amoxapine)
-- Aventyl (nortriptyline)
-- Celexa (citalopram hydrobromide)
-- Cymbalta (duloxetine)
-- Desyrel (trazodone hydrochloride)
-- Elavil (amitriptyline)
-- Effexor (venlafaxine hydrochloride)
-- Emsam (selegiline)
-- Etrafon (perphenazine/amitriptyline)
-- Lexapro (escitalopram hydrobromide)
-- Limbitrol (chlordiazepoxide/amitriptyline)
-- Ludiomil (maprotiline)
-- Luvox (fluvoxamine maleate)
-- Marplan (isocarboxazid)
-- Nardil (phenelzine sulfate)
-- Norpramin (desipramine hydrochloride)
-- Pamelor (nortriptyline)
-- Parnate (tranylcypromine sulfate)
-- Paxil (paroxetine hydrochloride)
-- Pexeva (paroxetine mesylate)
-- Prozac (fluoxetine hydrochloride)
-- Remeron (mirtazapine)
-- Sarafem (fluoxetine hydrochloride)
-- Seroquel (quetiapine)
-- Sinequan (doxepin)
-- Surmontil (trimipramine)
-- Symbyax (olanzapine/fluoxetine)
-- Tofranil (imipramine)
-- Tofranil-PM (imipramine pamoate)
-- Triavil (perphenazine/amitriptyline)
-- Vivactil (protriptyline)
-- Wellbutrin (bupropion hydrochloride)
-- Zoloft (sertraline hydrochloride)
-- Zyban (bupropion hydrochloride)

The APA said:

"We believe the new label, which still contains important warning information, reminds physicians and patients that antidepressants save lives. Physicians and patients need all the facts in order to make appropriate, informed decisions about any proposed course of treatment."

This change is not in any way an indictment of the medicines, it just acknowledges the reality that depression is dangerous.

Why is the risk apparently greater in younger people? It is thought that it has to do with the fact that the frontal lobes of the brain, that are involved in the control of emotions, have not yet fully formed.
 

Linking Depression, Diabetes and Alzheimer’s Disease

It has been known for many years that Alzheimer's disease and depression are associated with type 2 diabetes. Good control of blood glucose may reduce the risk of developing Alzheimer’s disease and depression, while treating depression may improve metabolic control.

Decreased levels of brain-derived neurotrophic factor (BDNF) have also been implicated in the pathogenesis of Alzheimer's disease and depression, and animal models have suggested that BDNF may play a role in insulin resistance.

So a group of scientists at The Centre of Inflammation and Metabolism, Department of Infectious Diseases at the University of Copenhagen in Denmark, decided to see whether BDNF plays a role in human glucose metabolism.

In the first study they looked at 233 people and found that BDNF was inversely associated with fasting plasma glucose, but not with insulin. In a second smaller study they did what are known as hyperglycemic and a hyperinsulinemic-euglycemic clamp studies, that allowed them to look at the relationships between BDNF, glucose and insulin. What they found was that output of BDNF from the brain was inhibited when blood glucose levels were elevated.

So it seems that low levels of BDNF accompany impaired glucose metabolism. Decreased BDNF may be a factor involved not only in dementia and depression, but also in type 2 diabetes, and it may be the missing link that explains the way in which the three conditions cluster together in epidemiological studies

This link between a chemical produced in the brain and diabetes is not altogether unexpected. The French physiologist Claude Bernard demonstrated that stimulation of the fourth ventricle of the brain caused glucose to rise, and it was later found that opiates put into this region of the brain could do the same thing.

This study reinforced the close links between metabolism and the brain, and gives us another reason for recommending that as we get older we must ensure that out glucose remains stable and that we do not become depressed.

Fats, Inflammation and Depression

We have talked before about the associations between inflammation and psychiatric illnesses.

There is yet more evidence in the shape of a study just published in the journal Psychosomatic Medicine. by Janice K. Kiecolt-Glaser and her colleagues from Ohio State University College of Medicine in Columbus.

The study involved 43 older adults with a mean age of 66.67 years, and the results suggests that the imbalance of omega-6 and omega-3 fatty acids in the typical American diet could be associated with the sharp increase in heart disease and depression seen over the past century. The more omega-6 fatty acids people had in their blood compared with omega-3 fatty acid levels, the higher their levels of the inflammatory mediators tumor necrosis factor-alpha and interleukin-6, and the greater the chance that they would suffer from depression. These are the same inflammatory mediators associated with insulin resistance, type 2 diabetes and coronary artery disease, all of which are more common in depression. And depression is more common in diabetes, arthritis and coronary artery disease than expected.

Our hunter-gatherer ancestors consumed two or three times as much omega-6 as omega-3, but today the average Western diet contains 15- to 17-times more omega-6 than omega-3. There were 6 individuals in the study who had been diagnosed with major depression, and they had nearly 18 times as much omega-6 as omega-3 in their blood, compared with about 13 times as much for subjects who didn't meet the criteria for major depression.

Depressed patients also had higher levels of tumor necrosis factor alpha, interleukin-6, and other inflammatory compounds. And as levels of depressive symptoms rose, so did the omega 6 and omega 3 ratio. So it seems as if the effects of diet and depression enhance each other. People who had few depressive symptoms and/or were on a well-balanced diet had low levels of inflammation in their blood. But when they became more depressed and their diets became worse – which is very common when people are depressed – then the inflammatory mediators in the blood surged.

Omega-3 fatty acids are found in foods such as fish, flax seed oil and walnuts, while omega-6 fatty acids are found in refined vegetable oils used to make everything from margarine to baked goods and snack foods. The amount of omega-6 fatty acids in the Western diet increased sharply once refined vegetable oils became part of the average diet in the early 20th century.

Depression alone is known to increase inflammation, the researchers note in their report, while a number of studies have found omega-3 supplements prevent depression.

So this more evidence for the value of eating fatty fish like salmon, mackerel or sardines two or three times a week, but be sure to avoid fish that may contain a lot of mercury. If you add more fruits and vegetables to your diet, you will also reduce your levels of omega-6 fatty acids.

I have just finished analyzing all the new literature on using fish oils for the prevention and treatment of psychological and psychiatric problems, and I am going to post my findings in the next couple of days.

Risky Advice About Bipolar Disorder

Sad to say, I see a lot of articles on medical topics that don’t make much sense. Most are well-meaning so I usually just let them go unless the suggestions are dangerous or unwise. I have just seen an unfortunate example of both.

The writer is talking about natural treatments for depression and bipolar disorder. He or she first divides depression into three groups: mild, major and severe.

I have not seen that done in many years and it betrays a real misunderstanding of the illness. People with genuine depression or bipolar disorder can get very ill very quickly, and these are illnesses in which as many as a quarter to a half of all sufferers attempt suicide. So it is risky to minimize the severity of the illness.

The writer then talks about “Bipolar Depression is a severe condition of depression that has manic undertones.”

This is simply not accurate. The “manic phase” of bipolar II disorder may be very mild, or present as intermittent anxiety or irritability. There is a great deal of discussion going on about the clinical features of all the different forms of bipolar disorder as we begin work on DSM-V. He or she appears here to be talking about “Mixed states,” about which, as it happens, I shall be lecturing tomorrow.

The author deserves kudos for saying that medications may be necessary, but the potentially dangerous thing was the advice to use St. John’s Wort in “Mild” cases of bipolar disorder. St. John’s Wort may have a role in the treatment of mild to moderate depression: the experts are still deliberating about that. But the problem of using it in bipolar disorder is that it may precipitate mania. One of several reasons for the changing clinical features of bipolar disorder in recent years is the over-prescription of antidepressants and self-medication. It is always difficult to prove causality, but here are a few papers on the dangers of using St. John’s Wort in people who may have bipolar disorder: 1, 2, 3, 4, 5, 6.

Integrated Medicine constantly uses conventional medicine together with natural approaches, and respects the psychological, subtle and spiritual aspects of any life challenge. But have to be very careful about how we combine different approaches so that we don't do more harm than good.

Be careful of advice that you read online!

Loss, Yearning and Acceptance

Like most doctors over the last forty years, I was raised on the works of Elisabeth Kübler-Ross.

She was a Swiss-born psychiatrist and the author of the influential book On Death and Dying, where she first discussed what is now known as the Kübler-Ross model.

She was born in Zürich, Switzerland, and interestingly was one of a set of identical triplets. She graduated from the University of Zürich medical school in 1957 and a year later moved to the United States to continue her studies.

As she began her practice, she later wrote that was appalled by the hospital treatment of patients who were dying. She began giving a series of lectures featuring terminally ill patients, forcing medical students to confront people who were dying. Her extensive work with the dying led to the publication of On Death and Dying in 1969. She wrote over 20 additional books on the subject of dying.

She also proposed the now famous Five Stages of Grief as a pattern of phases, most or all of which people tend to go through, in sequence, after being faced with the tragedy of their own impending death.

The five stages of grief are, in order:

1. Denial
2. Anger
3. Bargaining
4. Depression
5. Acceptance

The five stages have since also been adopted by many as applying to the survivors of a loved one's death. Some of us have also applied these stages to the understandng of people's psychological responses to chronic illness.

As influential as the theory has become, it has not, until now, been subjected to much research.

A study on the stages of grief was published in Journal of the American Medical Association at the end of February by researchers from Yale School of Medicine. The entire article is available for free download.

What they found was that in contrast to the Kübler-Ross model, yearning and acceptance are the two most salient emotions individuals experience after a significant loss.

The study was based on interviews with 233 bereaved individuals living in Connecticut between January 2000 and January 2003. The vast majority were spouses of the deceased and the remaining were adult children, parents, or siblings of the deceased.

The lead author Paul Maciejewski, assistant professor of psychiatry and director of the Statistical Modeling Core of Women's Health Research at Yale, had this to say:

"We found that disbelief was not the initial, dominant grief indicator. Acceptance is the norm in the case of natural deaths, even soon after the loss. And yearning, not depression, was the most common potentially adverse psychological response."

Yearning is one of the defining features of grief and is an emotion that most clearly reflects the absence of the deceased.

"Yearning is a longing for reunion with the deceased loved one, heartache about an inability to reconnect with this person. Individuals may cognitively accept the death of a loved one, but they may still pine for them and experience pangs of grief  (i.e. yearning)."

According to the study, disbelief, anger, and depression were not as prominent as yearning and acceptance. However, each grief indicator varied as a function of time  after the loss. In partial support of the stage theory, disbelief reached its peak immediately following the loss. Yearning, anger and depression reached their respective peaks at four, five and six months after the loss and acceptance reached its peak beyond six months after the loss.

These feelings peak and begin to decline by six months in the case of a natural death. Those who experienced the loss were more likely to be accepting of the death if it occurred within six months or longer after a diagnosis. The research confirmed what we see in clinical practice: deaths due to trauma or that occur within six months or less of diagnosis cause the most distress.

As Maciejewski said:

"The persistence of negative emotions beyond six months following the death reflect a more difficult than average adjustment and suggests a need for evaluation by a mental health professional and potential referral for treatment."

This is important research that gives all of us some practical guidance on how to understand, help and support people at a time of loss. It is also important to note that the study did not examine the mitigating effects of religious or spiritual beliefs, which we know can help people deal with loss.

After all, funerals are not held for the dead, but for the people left behind.

“Bereavement is a darkness, impenetrable to the imagination of the unbereaved."
--Iris Murdoch (Irish-born Writer and Philosopher, 1919-1999)

Teenage Mood Swings

How many of us have been perplexed by the violent mood swings of teenagers? One minute they are out skipping through the countryside and picking wild flowers. The next they seem intent on burning down the forest…

The mood swings and anxiety often make them seem as if they have some kind of "bipolar-lite."

An important new study has revealed that teenage mood swings may be explained by biological changes in the adolescent brain. The research is published in the journal Nature Neuroscience.

Sheryl Smith, a physiologist at the State University of New York, and her colleagues experimented on adolescent female mice and showed that their brains respond to stress in a different way from adults and pre-pubescent individuals.

Anxiety is highly complex and involves a cascade of chemical neurotransmitters and genes. One of its important regulators is the brain’s principal inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). GABA counteracts the effect of glutamate, an excitatory neurotransmitter in the limbic system of the brain. There is a kind of Yin/Yang relationship between GABA and glutamate.

The brain is full of what are known as “Neurosteroids:” steroid molecules that interact with  genes and receptors in nerve cells. Neurosteroids generally reduce anxiety, but this research shows that they promote anxiety in female mice around puberty via the selective desensitization of extrasynaptic GABA-A receptors.

Stress causes the release of a steroid known as 3α,5α-Tetrahydroprogesterone also known as Allopregnanolone or THP. In adult and pre-pubescent individuals THP increases the "calming" effect of GABA in the limbic system. However, Smith and her team found that THP had the opposite effect in adolescent mice. In other words the developing adolescent brain simply behaves differently

It would appear that THP has two roles, one in the limbic system where it helps to calm things down, and another in the hippocampus where in adolescents it heats things up. The hippocampus is important in memory and also in the regulation of emotion.

The underlying mechanism appears to be different levels of expression of a type of receptor known as the "alpha-4-beta-2-delta" GABA-A receptor in the hippocampal brain region known as CA1.

In adults and pre-adolescents there are few of these receptors and THP modulates and calms these regions of the brain.

However, in adolescents, the expression of these receptors is high, and the anxiety raising effect of THP in the hippocampus outweighs the calming effect it has in the limbic system.

Smith and her team were able to reverse the puberty effect in the mice by genetically altering the number of receptors.

The result of all this is that the teenage brain amplifies its reactions to stress. So whether the young person reacts by crying or being angry, the emotion will be much more pronounced than it would be in a pre-pubescent person or an adult. To adults it may seem like an overreaction, to the teenager it is his or her only response.

This study is thought to be the first to suggest an underlying physiological, as opposed to a psychological explanation for teenage mood swings.

Apart from raising understanding about what teenagers are going through, the finding raises the possibility of a new approach to more severe mood swings, such as bipolar disorder.

So It Goes

Like most young people, I did a load of menial jobs to pay my way through school. For one of them I spent a summer working as a hospital porter: I was the guy who pushed the wheelchairs around. There I met an interesting man who first introduced me to the works of Kurt Vonnegut, and by the end of the summer I had read all his books.

I just heard that Kurt passed away yesterday at the age of 84. He had an interesting life. He was captured by German troops in December 1944 during the Battle of the Bulge and he spent the rest of the war imprisoned in a Dresden slaughterhouse. On the night of 13 February 1945, Allied bombing raids flattened the city, creating a firestorm that killed an estimated 35,000 civilians in two hours. Vonnegut and his fellow prisoners survived because they were being kept in a cold meat locker three stories below the ground. When they emerged, there was nothing was left of the city. Vonnegut referred to his experiences of Dresden in several of his novels, most notably Slaughterhouse-Five that came out in 1967.

He often discussed his own mood disorder and a suicide attempt in the mid 1980s. His son, Mark Vonnegut is now a pediatrician, but his book Eden Express is an amazing account of his own descent into a mental illness that was described as schizophrenia, but from his description was far more likely to have been bipolar disorder.

They both survived, and for years now I have had all psychiatric trainees read Eden Express.

Here are a few of my favorite quotes from Kurt Vonnegut.

• “1492. As children we were taught to memorize this year with pride and joy as the year people began living full and imaginative lives on the continent of North America. Actually, people had been living full and imaginative lives on the continent of North America for hundreds of years before that. 1492 was simply the year sea pirates began to rob, cheat, and kill them.”
• “A purpose of human life, no matter who is controlling it, is to love whoever is around to be loved.”
• “All of us were stuck to the surface of a ball incidentally. The planet was ball-shaped. Nobody knew why we didn’t fall off, even though everybody pretended to kind of understand it.”
• “All time is all time. It does not change. It does not lend itself to warnings or explanations. It simply is. Take it moment by moment, and you will find that we are all, as I've said before, bugs in amber.”
• “Another flaw in the human character is that everybody wants to build and nobody wants to do maintenance.”
• “Any reviewer who expresses rage and loathing for a novel is preposterous. He or she is like a person who has put on full armor and attacked a hot fudge sundae.”
• “Beware of the man who works hard to learn something, learns it, and finds himself no wiser than before... He is full of murderous resentment of people who are ignorant without having come by their ignorance the hard way.”
• “Charm was a scheme for making strangers like and trust a person immediately, no matter what the charmer had in mind.”
• “During my three years in Vietnam, I certainly heard plenty of last words by dying American foot soldiers. Not one of them, however, had illusions that he had somehow accomplished something worthwhile in the process of making the Supreme Sacrifice.”
• “He adapted to what there was to adapt to.”
• “(He) told us about one of Plato’s dialogues, in which an old man is asked how it felt not to be excited by sex anymore. The old man replies that it was like being allowed to dismount from a wild horse.”
• “Here is a lesson in creative writing. First rule: Do not use semicolons. They are transvestite hermaphrodites representing absolutely nothing. All they do is show you've been to college.”
• “Here's what I think the truth is: We are all addicts of fossil fuels in a state of denial, about to face cold turkey.”
• “How nice--to feel nothing, and still get full credit for being alive.”
• “Humor is an almost physiological response to fear.”
• “I am eternally grateful.. for my knack of finding in great books, some of them very funny books, reason enough to feel honored to be alive, no matter what else might be going on.”
• “I can have oodles of charm when I want to.”
• “I say in speeches that a plausible mission of artists is to make people appreciate being alive at least a little bit. I am then asked if I know of any artists who pulled that off. I reply, 'The Beatles did'.”
• “I think that novels that leave out technology misrepresent life as badly as Victorians misrepresented life by leaving out sex.”
• “I want to stay as close to the edge as I can without going over. Out on the edge you see all kinds of things you can't see from the center.”
• “I'm suing a cigarette company because on the package they promised to kill me, and yet here I am.”
• “I’ve got at least one tiny corner of the universe I can make just the way I want it . . .”
• “If somebody says, 'I love you,' to me, I feel as though I had a pistol pointed at my head. What can anybody reply under such conditions but that
• which the pistol-holder requires? 'I love you, too.'”
• “If you can do a half-assed job of anything, you're a one-eyed man in a kingdom of the blind.”
• “It is harder to be unhappy when you are eating.”
• “Just because some of us can read and write and do a little math, that doesn't mean we deserve to conquer the Universe.”
• “Laughter and tears are both responses to frustration and exhaustion. I myself prefer to laugh, since there is less cleaning up to do afterward.”
• “Life happens too fast for you ever to think about it.  If you could just persuade people of this, but they insist on amassing information.”
• “. . . life, by definition, is never still.”
• “Like so many Americans, she was trying to construct a life that made sense from things she found in gift shops.”
• “Love is where you find it.”
• “Love may fail, but courtesy will prevail.”
• “Maturity is a bitter disappointment for which no remedy exists, unless laughter can be said to remedy anything.”
• “. . . most of the world’s ills can be traced to the fact that Man’s knowledge of himself has not kept pace with his knowledge of the physical world.”
• “Much of the conversation in the country consisted of lines from television shows, both present and past.”
• “New knowledge is the most valuable commodity on earth. The more truth we have to work with, the richer we become.”
• “One of the few good things about modern times: If you die horribly on television, you will not have died in vain. You will have entertained us.”
• “Say what you will about the sweet miracle of unquestioning faith, I consider a capacity for it terrifying and absolutely vile!”
• “Thanks to TV and for the convenience of TV, you can only be one of two kinds of human beings, either a liberal or a conservative.”
• “The chief weapon of sea pirates, however, was their capacity to astonish. Nobody else could believe, until it was too late, how heartless and greedy they were.”
• “The secret to success in any human endeavor is total concentration.”
• “There is a tragic flaw in our precious Constitution, and I don't know what can be done to fix it. This is it: Only nut cases want to be president.”
• “. . . there is this feeling that I have a destiny far away from the shallow and preposterous posing that is our life . . .”
• “Those who believe in telekinetics, raise my hand.”
• “. . . uncritical love is the only real treasure.”
• “We all missed a lot. We’d all do well to start again, preferably with kindergarten.”
• “We are what we pretend to be, so we must be careful about what we pretend to be.”
• “We could have saved the Earth but we were too damned cheap.”
• “Well, the telling of jokes is an art of its own, and it always rises from some emotional threat. The best jokes are dangerous, and dangerous because they are in some way truthful.”
• “What had made me move through so many dead and pointless years was curiosity.”

Psychological Problems, Stigma and Success

I do a lot of work to try and de-stigmatize mental illness, and to emphasize that all of my experience and all the scientific evidence makes it very clear that most psychological and psychiatric problems lie on a spectrum. We define something as an "illness" only if it is causing suffering or distress.

Because of my work I know about the physical and psychological problems of a great many people in the public eye, but I will obviously not talk about people unless they decide to say something themselves.

When I am speaking to politicians or the media I often show them a list of some of the people with psychological problems who have gone public.

I just found this long list of Deborah Serani's blog. There were a number of names of people whom I did not know had revealed that they had suffered from problems. I am pleased that Deborah offered some references. I have also added a few names from my own research.

If there are any mistakes, please let me know and I shall correct them.

I would like to make three points:

1. Psychological problems and psychiatric illnesses are common and usually treatable
2. Having been diagnosed with one of these problems does not preclude you from outstanding success
3. This list does not include people with substance abuse problems, though these problems are usually as physical as any other

I do hope that you will find it helpful to see just how many terrific people have had their downs as well as their ups!

John Quincy Adams (US President)
Alvin Ailey (Choreographer)
Lionel Aldridge (Football Star)
Buzz Aldrin (Astronaut)
Adam Ant  A.K.A. Stuart Goddard (Singer)
Ann-Margaret (Actor)
Louie Anderson (Comedian Actor)
Gillian Anderson (Actress)
Fiona Apple (Musician)
Diane Arbus (Photographer)
Isaac Asimov (Author)
Drew Barrymore (Actor/Producer)
Daniel Boorstin (Former Us Presidential Adviser)
Zach Braff (Actor)
Art Buchwald (Columnist)
Oksana Baiul (Skating Star)
Kim Basinger (Actress)
Ned Beatty (Actor)
Syd Barrett (Musician)
Ludwig Van Beethoven (Composer)
Maurice Bernard (Actor)
Irving Berlin (Composer)
Danny Bonaduce (Actor/Radio DJ)
Halle Berry (Actor)
Kjell Magne Bondevik (Prime Minister of Norway)
Steve Blass (Baseball Star)
Charles “Buddy” Bolden (Musician)
Robert Borrstin (Political Advisor)
David Bowie (Singer)
Marlon Brando (Actor)
Jeremy Brett (Actor)
Charlotte Bronte (Author)
Robert Burns (Poet)
Willie Burton (Athlete)
Barbara Bush (Former First Lady - U.S.)
Delta Burke (Actor)
Carol Burnett (Actress/Comedian)
Lord Byron (Poet)
Cher (Singer/Actress)
Dick Clark (Producer/Music Magnate)
John Candy (Comedian)
Ray Charles (Musician)
Deanna Carter (Singer)
Helen Caldicott (Activist/Writer)
Dean Cain (Actor)
Drew Carey (Actor/ Comedian)
Earl Campbell (Football Star)
Eric Clapton (Musician)
Jim Carrey (Actor/Comedian)
Melanie Chisholm (Singer)
Naomi Campbell (Model)
Rosemary Clooney(Singer)
Jose Canseco (Baseball Star)
Shawn Colvin (Musician)
Mary Jo Codey (First Lady Of New Jersey)
Judy Collins (Musician)
Dick Cavett (TV Host/Writer)
Courtney Cox (Actor)
Margaret Cho (Actor/Comedian)
Natalie Cole (Singer)
Michael Crichton (Writer)
Francis Ford Coppola (Director)
Sheryl Crow (Musician)
Winston Churchill (English Prime Minister)
Nicolas Cage (Actor)
Sandra Cisneros (Writer)
Patricia Cornwell (Writer)
John Cleese (Comedian/Actor)
Leonard Cohen (Musician)
Paula Cole (Actor)
Shayne Corson (Hockey Star)
Judy Collins (Musician)
Shawn Colvin (Musician)
Jeff Conaway (Actor)
Ty Cobb (Baseball Star)
Pat Conroy (Writer)
Billy Corgan (Musician)
Calvin Coolidge (US President)
Bill Dana (Comedian)
John Daly (Golf Star)
Rodney Dangerfield (Comedian/ Actor)
Charles Darwin (Scientist)
Jefferson Davis (President Of The Confederate States Of America)
Jonathan Davis (Musician)
Sandra Dee (Actor)
Gaetano Donizetti (Opera Singer)
Mike Douglas (TV Host)
Walt Disney (Entrepreneur)
John Denver (Musician)
Dame Edna Everage a.k.a. Barry Humphries (Comedian)
Ellen Degeneres (Comedian/Actor)
Richard Dreyfuss (Actor)
Johnny Depp (Actor)
Paolo Dicanio (Soccer Star)
Eric Douglas (Actor)
Charles Dickens (Author)
Patty Duke (Actress)
Scott Donie (Olympic Star)
Kitty Dukakis (Former First Lady Of Massachusetts)
Michael English (Singer)
Jim Eisenreich (Baseball Star)
Thomas Edison (Inventor)
Ralph Waldo Emerson (Writer)
Robert Evans (Film Producer)
Jules Feiffer (Cartoonist)
James Farmer (Civil Rights Leader)
Edie Falco (Actress)
Betty Ford (Former US First Lady)
Carrie Fisher (Actress)
James Forrestal (Undersecretary Of US)
Eddie Fisher (Singer)
Aretha Franklin (Singer)
Harrison Ford (Actor)
Albert French (Writer)
Sally Field (Actress)
Connie Francis (Singer)
Sarah Ferguson (Duchess Of York)
Sigmund Freud (Psychoanalyst)
Stephen Fry (Actor)
Shecky Greene (Comedian)
Barbara Gordon (Filmmaker)
Phil Graham (Washington Post)
James Gandolfini (Actor)
James Garner (Actor)
Peter Gabriel (Musician)
Kendall Gill (Basketball Star)
Ruth Graham (Writer)
John Gibson (Pianist)
Danny Glover (Actor)
Dwight Gooden (Baseball Star)
Tipper Gore (Former US First Lady)
Galileo (Scientist)
Carey Grant (Actor)
Mariette Hartley (Actor/Activist)
Tim Howard (Soccer Star)
Juliana Hatfield (Musician)
Ernest Hemingway (Writer/ Nobel Laureate)
Margaux Hemingway (Actor)
Audrey Hepburn (Actor/Activist)
Olivia Hussey (Actress)
Pete Harnisch (Baseball Star)
Linda Hamilton (Actor)
Stephen Hawking (Physicist)
Sir Anthony Hopkins (Actor)
Marty Ingels (Comedian)
Janet Jackson (Musician)
Kay Redfield Jamison (Psychologist/Author)
Richard Jeni (Comedian)
Jim Jenson (Newscaster)
Billy Joel (Musician)
Beverly Johnson (Supermodel)
Elton John (Musician)
Angelina Jolie (Actor/Activist)
Daniel Johns (Musician)
Ashley Judd (Actor)
Naomi Judd (Singer)
Al Kasha (Songwriter)
Danny Kaye (Actor)
Leila Kenzle (Actress)
John Keats (Poet)
Franz Kafka (Writer)
Gelsey Kirkland (Dancer)
Margot Kidder (Actress)
Nicole Kidman (Actress)
Joey Kramer (Musician)
Julie Krone (Star Athlete)
Pat Lafontaine (Hockey Star)
Jessica Lange (Actor)
Robert E. Lee (US General)
Jacob Lawrence (Artist)
Vivien Leigh (Actress)
Peter Nolan Lawrence (Writer)
Primo Levi (Writer)
John Lennon (Musician)
Meriwether Lewis (Explorer)
Courtney Love (Singer)
Allie Light (Director)
Abraham Lincoln (American President)
Rick London (Cartoonist)
Mary Todd Lincoln (Former US First Lady)
Salvador Luria (Scientist/Nobel Laureate)
John Madden (Football Star)
Meat Loaf (Musician/Actor)
Camryn Manheim (Actor)
Martha Manning (Psychologist)
Gustav Mahler (Composer)
Alanis Morisette (Singer)
Howie Mandel (Comic)
Bette Midler (Singer/Actress)
Dave Matthews (Musician)
Gary Mcdonald (Actor)
A.J. Mclean (Musician)
Burgess Meredith (Actor)
Sir Paul Mccartney (Musician)
Robert Mcfarlane (Security Advisor)
Sarah Mclachlan (Musician)
Rod Mckuen (Writer)
Gary Mcdonald (Actor)
Les Murray (Poet)
John Stuart Mill (Philosopher)
J.P. Morgan (Industrialist)
Edvard Munch (Artist)
John Mellencamp (Musician)
Paul Merton (Comedian)
Kate Millet (Writer/Feminist)
Carmen Miranda (Dancer)
Claude Monet (Artist)
Many Moore (Singer)
Michelangelo (Artist)
V.S. Naipaul (Writer/Nobel Laureate)
John Nash (Mathematician /Nobel Prize)
Ralph Nader (Consumer Rights Advocate)
Stevie Nicks (Musician)
Vaclav Nijinsky (Dancer)
Sir Isaac Newton (Scientist)
Deborah Norville (Journalist)
Marie Osmond (Entertainer)
Sir Laurence Olivier (Actor)
Rosie O’Donnell (Comedian/Actress)
Georgia O’Keefe (Artist)
Donny Osmond (Entertainer)
Lani O'Grady (Actress)
Eugene O'Neill (Playwright)
Dolly Parton (Musician)
Meera Popkin (Broadway Star)
Charley Pell (Football Coach)
George Patton (US General)
Jane Pauley (Journalist)
Teddy Pendergrass (Musician)
Edgar Allan Poe (Writer)
Elvis Presley (Entertainer)
Ezra Pound (Poet)
Jason Pollock (Artist)
Cole Porter (Composer)
Jimmy Piersall (Baseball Star)
Alma Powell (Wife Of General Colin Powell)
Susan Powter (Motivational Speaker)
Freddie Prinze Jr. (Actor)
Roseanne (Comedian/Actress)
Bonnie Raitt (Musician)
Burt Reynolds (Actor)
Lou Reed (Musician)
Norman Rockwell (Artist)
Theodore Roosevelt ( President Of The United States)
Joan Rivers (Comedian Actress)
Mac Rebennack A.K.A. Dr. John (Musician)
Alex Rodriguez (Baseball Star)
Alys Robi (Vocalist)
Axel Rose (Singer)
Winona Ryder (Actress)
Yves Saint Laurent (Fashion Designer)
Sam Shepard (Playwright)
Tom Snyder (TV Host)
Monica Seles (Tennis Star)
Linda Sexton (Writer)
Neil Simon (Playwright)
William T. Sherman (US General)
Marc Summers (TV Host)
Diana Spencer (Princess Of Wales)
John Steinbeck (Author)
Paul Simon (Musician)
Lauren Slater (Writer)
Willard Scott (Star Weatherman)
William Shakespeare (Writer)
Carly Simon (Singer)
Jose Solano (Actor)
Rick Springfield (Musician/Actor)
Brooke Shields (Model/Actress)
Rod Steiger (Actor)
George Stephanopoulos (Political Advisor)
Barbra Streisand (Singer/Actress)
William Styron (Writer)
Charles Schulz (Cartoonist)
Teresa Stratas (Opera Singer)
Sissy Spacek (Actress),
Dave Stewart (Singer)
Darryl Strawberry (Baseball Star)
Lori Schiller (Writer)
Francis Sherwood (Writer)
Scott Simmie (Journalist)
Earl Simmons A.K.A. DMX (Musician/Actor)
Alonzo Spellman (Football Star)
Nikola Tesla (Inventor)
Spencer Tracy (Actor)
Hunter Tylo (Actor)
Leo Tolstoy (Author)
Ted Turner (Entrepreneur)
Henri De Toulouse-Lautrec (Artist)
Mark Twain (Author)
Peter Illyich Tchaikovsky (Composer)
Anne Tyler (Author)
Tracy Ullman (Actor)
Dimitrius Underwood (Football Star)
Vivian Vance (Actor)
Kurt Vonnegut (Writer)
Tom Waits (Musician)
Mike Wallace (Journalist)
Michael Warren (Editor Canada Post)
George Washington (US President)
Evelyn Waugh (Novelist)
Damon Wayans (Comedian/Actor)
Tennessee Williams (Writer)
Dar Williams (Musician)
Robin Williams (Comedian/Actor)

Ann Wilson (Singer)
Bill Wilson (Founder Of Alcoholics Anonymous)
Brian Wilson (Musician)
Oprah Winfrey (TV Host)
Jonathan Winters (Comedian)
Ed Wood (Director)
Tom Wolfe (Writer)
Lewis Wolpert (Scientist)
Hugo Wolf (Composer)
Virginia Woolf (Novelist)
Luther Wright (Basketball Star)
W.B. Yeats (Poet)
Robert Young (Actor)
Bert Yancey (Golf Star)
William Zeckendorf (Industrialist)
Renee Zellweger (Actor)


References
Buchwald, A. (1999). Famous, important people who have suffered depression. Psychology Today.

Fonda, J. (2005). My life, so far. New York: Random House.

Jamison, K.R. (1993). Touched with fire. Manic depressive illness and artistic temperment. New York: Free Press.

Shepard, S. (1999). Mrs. gore breaks the ice on mental illness. Wahsington Bureau: The Palm Beach Post.

Shields, B. (2005). Down came the rain: My journey through post partum depression.
New York: Hyperion Books.

______(2005). Health: Celebrities who have admitted suffering from depression. England: Burmingham Post.

People with Mental Illness Enrich Our Lives
http://www.nami.org/helpline/peoplew.htm

Celebrity with Anxiety Disorders
http://www.anxietysecrets.com/celebrities.htm

Famous People Who Have Battled Depression
http://www.funkstop.com/ed/depression

Hormones, Addictions and Mood

People working with mental illness have been for years now been puzzled by two observations. The first is that mood disorders and schizophrenia follow quite different trajectories in men and women. Women tend to be more vulnerable to mood disorders and if they get schizophrenia it tends to be less severe and to have fewer "negative" symptoms, such as flat, blunted or constricted affect and emotion, poverty of speech and lack of motivation until after menopause. We have looked at some of the reasons for the different rates of mood disorder, in terms of relationships and social pressures, but there must also be a biological component. The second puzzle is that women are more vulnerable to addictive drugs in the days before they ovulate.

New research published in the  Proceedings of the National Academy of Sciences may provide part of the answer to both puzzles.

Colleagues at the National Institute of Mental Health (NIMH), a component of the National Institutes of Health (NIH), have conducted a fascinating imaging study that has shown that fluctuations in levels of sex hormones during women's menstrual cycles affect the responsiveness of the reward systems in the brain.

The reward system circuits include the:

• Prefrontal cortex, which has key roles in thinking, planning and in the control of our emotions and impulses
• Amygdala, which is involved in rapid and intense emotional reactions and the formation of emotional memories
• Hippocampus, which is involved in learning, memory and navigation
• Striatum that relays signals from these areas to the cerebral cortex

It has been known for some time that neurons in the reward circuits are rich in estrogen and progesterone receptors. However, how these hormones influence reward circuit activity in humans has remained unclear.

The researchers used functional magnetic resonance (fMRI) imaging to examine brain activity of 13 women and 13 men while they performed a task that involved simulated slot machines. The women were scanned while they did the task, both before and after ovulation.

When anticipating a reward, in the pre-ovulation phase of their menstrual cycles the women showed more activity in the amygdala and frontal cortex. When women were actually winning prizes, their reward systems were more active if they were in the phase of their menstrual cycle preceding ovulation. This phase of the cycle is dominated by estrogen, compared to postovulatory phase when estrogen and progesterone are both present. When winning, the main systems that became active were in the parts of the brain involved in pleasure and reward.

The researchers also demonstrated that the reward-related brain activity was directly linked to levels of sex hormones. Activity in the amygdala and hippocampus was in directly linked to estrogen levels, regardless of where a woman was in her cycle. When women won prizes during the post-ovulatory phase of the cycle, progesterone modulated the effect of estrogen on the reward circuit.

Men showed a different activation profile from women during both anticipation and delivery of rewards. Men had more activity in the striatum during anticipation compared with women. On the other hand, women had more activity in a frontal cortex when they won prizes.

This research could have a number of important implications. The most obvious is that it confirms what many women know already: they are more likely to take addictive substances or to engage in pleasurable - but perhaps impulsive or risky - behaviors just before they ovulate.

It is not difficult to imagine why this might have developed during evolution.

“Coming to terms with the rhythms of women's lives means coming to terms with life itself, accepting the imperatives of the body rather than the imperatives of an artificial, man-made, perhaps transcendentally beautiful civilization. Emphasis on the male work-rhythm is an emphasis on infinite possibilities; emphasis on the female rhythms is an emphasis on a defined pattern, on limitation.”
--Margaret Mead (American Anthropologist and Writer, 1901-1978)

Toxoplasmosis and Behavior

Last August I wrote an article about some extraordinary new evidence implicating Toxoplasma gondii in some psychological and psychiatric illnesses. Latent infection with Toxoplasma gondii is amongst the most prevalent of human infections and it had been generally assumed that it is asymptomatic unless there is congenital transmission or reactivation because a person has an immune system that has become depressed or compromised. That assumption is being completely re-evaluated. 

The article generated some extremely interesting correspondence and some spirited discussions.

Here is a very insightful letter from a physician:

Dear Dr. Petty,

I thought about the concept of psychological illness caused by a virus or other organism. I was wondering what would be the mode of dispersion of such a virus. Upper respiratory tract infections, skin and gastrointestinal infections spread by cough, by touch and hand to mouth respectively. How would such a brain virus or protozoal organism promote itself? Of course it could be by the above methods but it seems that there should some way that the specific disease process is connected to a behavior that helps it to spread itself. 

Then I got to thinking; diseases have learned physical ways to disseminate themselves, I wonder if a disease could change behavior to promote it's own dissemination and survival? I imagine that if that were true, people with the flu would be sociable, people with infectious diarrhea would be sociable and hungry, people with AIDS would have increased libido. I haven't yet seen any data for this. Although I've always felt that there was one disease that did alter behavior in a way that is conducive to disseminating itself, and that is rabies. The host goes from being docile, to seeing all others as the enemy. He then attacks them, bites them and thus passes on the organism. A true mind altering virus, although it's psychology works better with animals than with people. Do you think that there are other diseases that spread purely by behavior, that cause the host to seek out the next host and not just pass the disease from one to another just due to proximity?

This was my response:

What great questions!

And believe it or not, there's quite a lot of empirical research on these very topics.

There is a whole textbook on the behavioral effects of parasites edited by Janice Moore entitled  Parasites and the Behavior of Animals. Here's an interesting one: rats and mice are hard wired to avoid cats. Millions of years of programming have ensured that Tom's very presence would send Jerry packing. Cats carry Toxoplasma gondii and if mice or rats become infected with it, usually by eating cat poop, they lose their fear of felines. So now Tom can have lunch at his leisure.

I've also talked about the way in which people with creativity and schizotypal personality disorder (i.e. carriers of genetic risk) tend to be promiscuous, while people with schizophrenia have fewer children. Both groups tend to get more sexually transmitted diseases than the general population. It would be tempting to think that toxoplasmosis can be spread that way, however there's a 32-year old study in German that showed that Toxoplasma was not transmitted by intercourse. However, cytomegalovirus, a common partner to Toxoplasma may be. And both modulate dopamine activity in the regions of the brain involved in salience.

I have done a very detailed literature search encompassing papers written in all the languages that I can read, and have not been able to find any clear evidence of behavior change induced by HIV, influenza or infectious diarrhea: what interesting and important questions to research.

We do have some more data confirming the effects of Toxoplasma infections on the behavior of rats: they become less anxious and therefore do not respond to environmental threats as quickly as uninfected rodents. An antipsychotic medication (haloperidol), a mood stabilizer (valproic acid) and two chemotherapeutic agents - pyrimethamine or Dapsone – have all been shown to prevent the development of Toxoplasma-induced behavioral change.

Another recent study from the Departments of Parasitology, Microbiology and Zoology, Charles University, the Centre of Reproductive Medicine and GynCentrum, in the Czech Republic also speaks to the significance of latent Toxoplasma infections: the presence of the parasite in the blood of pregnant women increases their chance of giving birth to boys. The increased survival of male embryos in infected women may be explained by Toxoplasmosis infections modulating and suppressing the immune system.

If Toxoplasma plays a part in the development of some psychiatric illnesses, yet a high proportion of the population carries it without any problems, one obvious question is what activates it? Environmental stress might, perhaps, cause the Toxoplasma to become reactivated and play a part in the development of specific psychiatric symptoms.

This story is continuing to develop and I am going to watch it closely. If it is confirmed, it could open up some brand new avenues for helping treat and perhaps even prevent some types of psychiatric illness.

Genetic Testing in the Treatment of Depression

By a remarkable “coincidence,” less than a week after the appearance of two items (1. 2.) questioning the value of using genetic testing to help predict response to treatment in people suffering from depression, an important report has been released today.

The report is supported by a collaboration of the Agency for Healthcare Research and Quality and the Centers for Disease Control (CDC) and Prevention’s National Office of Public Health Genomics, and it was the CDC that funded it.

It is gratifying to see that the findings of the report are identical to those published in the two articles last week. The main conclusion of the report is that there is insufficient evidence to determine if current gene-based tests intended to personalize the dose of medications in a class of drugs called selective serotonin reuptake inhibitors (SSRIs) improve patient outcomes or aid in treatment decisions in the clinical setting.

The investigators reviewed 1,200 abstracts that led to the final inclusion of 37 articles. As we learned last week, the evidence indicates the existence of tests with high sensitivity and specificity for detecting only a few of the more common known polymorphisms of the cytochromes 2D6, 2C19, 2C8, 2C9, and 1A1.

They found mixed evidence regarding the association between CYP450 genotypes and SSRI metabolism, efficacy, and tolerability in the treatment of depression, mainly from a series of heterogeneous studies in small samples.
There were no data regarding:

1. If testing for CYP450 polymorphisms in adults starting SSRI treatment for non-psychotic depression leads to improvement in outcomes versus not testing, or if testing results are useful in medical, personal, or public health decision making.
2. If CYP450 testing influences depression management decisions by patients and providers in ways that could improve or worsen outcomes.
3. If there are direct or indirect harms associated with testing for CYP450 polymorphisms or with subsequent management options.

This report confirms that there is little point in doing these genetic tests.

It also raises another point. It is now some years since some of these tests became available commercially. If they were really of value then we have to ask why there hasn’t been an avalanche of research on the topic – especially by the people marketing the tests – and why none of major psychopharmacology groups in the United States, Europe, Japan or Australia picked up on the tests. I probably know most of the people in these hospitals, universities and research centers and none has been much interested in this work.

So when someone suggests that you undergo some new test or investigation, remember to use your common sense. If there is only one person doing it - whether it’s a genetic test, a brain scan, some non-standard type of thyroid or adrenal test, or a Vega test - ask why nobody else is using it and why nobody has published any decent research on the method.

When it comes to your health use your common sense, your intuition and impartial information to be your guide and your support.

Growing Evidence for the Efficacy of Homeopathic Medicine

When you first hear about homeopathy it sounds like utter nonsense: "like curing like"; vital forces; miasms and super-dilute remedies that no longer contain a single molecule of the original substance.

The trouble is that - apart from two centuries of clinical experience - there is a respectable and growing body of evidence that there is indeed something to homeopathy. David Reilly from the Center for Integrative Care in Glasgow, Scotland, has written a very useful paper that is available for free download.

Over in the "Resources" section on the left hand side of the blog I have a link to a reading list that I put together for Amazon.com.

There are many good introductory books on homeopathy, and I have mentioned some of the best. There are also a few books that delve into some of the science that could well provide a mechanism by which homeopathy may work.

In the coming weeks I shall be putting together some more reading list as well as summaries of the research into this fascinating field.

There is a final point. Homeopathic medicines, Flower essences and many forms of "Energy medicine" seem to have been becoming more effective over the last few decades, and this observation was one of the reasons for believing that New Laws of Healing are emerging.

Let me give you a simple example. Two weeks ago, I heard about a woman in the first trimester of pregnancy was being seen because of a quite severe mood problem. She had such severe morning sickness that she asked to have a trash can positioned next to her chair. Many experts believe that morning sickness begins as a reflex to expel food toxins that might harm the baby, but then develops into a neurologically-mediated cycle.

The patient had never heard of homeopathy and probably did not understand why she was asked some apparently irrelevant questions. She answered that she would feel better in the evening, if she applied pressure or a wash cloth to her stomach. She also reported that the sudden cold spell had made her much worse, and that stress and spicy foods made her much worse.

She was given the remedy Nux vomica in a very low potency. The nausea and vomiting stopped immediately, never to return. And her mood - which had been bad for many months before she became pregnant - also improved.

This is another one of those "N of one" reports, and the plural of anecdote is not data. But I was trained by homeopaths, some of whom had been in practice since the 1930s, and all had sat at the feet of some of the greatest homeopaths on the last century. Yet they all said that problems like morning sickness normally need repeated treatments over several days. Not a single treatment and it's gone.

If you keep you eyes open you will be amazed to see how the efficacy of some forms of treatment appear to be getting better, while some others are becoming less effective with time.

Predicting Response to Medicines

Much as we would all like to rely upon natural and non-invasive approaches to treatment, there are times when pharmaceuticals also have their place.

A common question is whether there are any good ways to predict who will respond to what treatment and whether we can predict the risk of side effects. Unfortunately the answer is that although we are getting better, and the research base if growing rapidly, there is still a lot of trial and error in prescribing.

An exciting and relatively new area is called pharmacogenetics: using our genetic make-up to allow us to tailor treatments to each of us individually. Over the last few months there have been a lot of media reports about being able to use simple blood tests to predict who will respond to antidepressants. (As an example, see this report from the Washington Post).

Unfortunately these reports, though undoubtedly well meaning, have not told the whole story. You might be interested to see a brief article about this interesting topic that helps put things in perspective.

Though there are some highly reputable institutions that are trying to help provide genetic testing not only for drug responses but also to predict the risk of developing certain illness, unfortunately there are also plenty of rogues who prey upon the worried and unwary. I was recently shown pages and pages of all kinds of tests on an individual: genetic tests; biochemical tests; allergy tests and all kinds of unorthodox tests using every imaginable type of gizmo, from magnets to devices claimed to measure the aura.

Not surpringly, the individual was thoroughly confused by this vast morass of information. The best thing to do was to tear it all up and to start again with the simple question: "What do you think is wrong?" Deep down inside, she knew the answer.

I have spent years working in and running laboratories, so I am not shy about using science and technology.

Science and technology must be our servants and not our masters.

“During my eighty-seven years, I have witnessed a whole succession of technological revolutions. But none of them has done away with the need for character in the individual or the ability to think.”
--Bernard Mannes Baruch (American Financier and Government Official, 1870-1965)

“We must learn to balance the material wonders of technology with the spiritual demands of our human race."
--John Naisbitt (American Futurist and Author, 1929-)

“Humanity has passed through a long history of one-sidedness and of a social condition that has always contained the potential of destruction, despite its creative achievements in technology. The great project of our time must be to open the other eye: to see all-sidedly and wholly, to heal and transcend the cleavage between humanity and nature that came with early wisdom.”
--Murray Bookchin (American Ecologist, 1941-)

How We Plan the Future

One of our most remarkable abilities is our capacity for creating a mental picture of events that have not yet happened. It certainly appears that many animals can do something similar, but the human ability to wait and to plan seems to be almost unique. Though with all the recent advances in our understanding about the emotional and cognitive skills of many animal species, I am wary about making too many claims about human specialness.

There is some fascinating research in today’s issue of the Proceedings of the National Academies of Sciences.

Investigators from Washington University in St. Louis, have performed a set of experiments that will not only help us better understand what goes wrong in some diseases, but may ultimately help all of us to become better at visualizing.

They compared the functional MRI scans of 21 healthy volunteers when they were asked either to vividly imagine future events or to recollect past memories.

The images showed clear differences between imagining a birthday already experienced and a birthday yet to come.

In particular, when looking ahead, there were three particular areas of the brain that became activated - the left lateral premotor cortex, the left precuneus and the right posterior cerebellum. These areas of the brain are already known to be involved when we imagine executing body movements, suggesting that when the brain is thinking about the future, it does so in terms of distinct movements and actions that will happen at that point.

The research provides powerful support for the idea that memory and thought about the future are highly interrelated and may help explain why future thought may be impossible without memories.

Other research has shown that when volunteers are asked to think about playing baseball they activate the part of the brain involved in swinging the arm. You will now see the link with the item that I posted yesterday about learning to tango!

These findings are consistent with observations on people who have sustained damage to these regions of the brain: they lose the ability to think ahead. There is a small amout of data to suggest that some of these same regions do not function properly in some people diagnosed with antisocial personality disorder, most of whom have a reckless disregard for the consequences of their actions.

People with depressive disorders often find it very difficult to generate a positive image of the future, in part  because their memory is impaired by the depression.

In classes we have also found that if people maintain complete stillness while visualizing it is quite different from moving and doing the physical actions as you visualize.

Try it for yourself and see what I mean.

“Man can only become what he is able to consciously imagine or to “image forth.”
--Dane Rudhyar (a.k.a. Daniel Chenneviere, French-born American Composer, Theosophist and Astrologer, 1895-1985)

“I am thought. I can see what the eyes cannot see. I can hear what the ears cannot hear. I can feel what the heart does not feel.”
-- Peter Nivio Zarlenga

Acupuncture and Depression

I have been using acupuncture for over 25 years and one of the reasons for doing my advanced training in China was to examine its use in neurological and psychiatric disorders.

It was interesting to discover that even in hospitals specializing in traditional Chinese medicine, the doctors usually used conventional antidepressants and antipsychotics rather than acupuncture, although I had seen many Western acupuncturists claim that they could treat depression.

My own experience with treating acupuncture has been disappointing. By contrast, it is often very good indeed for anxiety, and I have shown many people how to follow up with simple acupressure if they experience anxiety or panic.

There is new research that seems to endorse my lack of success in treating depression and why the Chinese doctors used Western medicine. There had been a number of small studies (e.g. 1. 2. 3. 4. 5. 6.) of acupuncture in depression that had shown promise, as well as some huge Chinese studies that had claimed good results.

One of the problems with much of the Chinese research is that it is normally done without control groups and with very broad criteria. Many only rate whether someone is “cured,” “much better” or “no better.”

Despite the promise of the early studies, three recent reviews (1. 2. 3.) suggested that the evidence for acupuncture in depression was inconclusive.

This new study was published in the Journal of Clinical Psychiatry in November of this year and involved 151 patients with Major Depressive Disorder. The study ran for four years. This was a well-conducted clinical trial by researchers who had originally found some promising results in a pilot study (Allen JBJ, Schnyer RN, Hitt SK. The efficacy of acupuncture in the treatment of major depression in women. Psychological Science 1998; 9: 397-401). Although well tolerated, the research failed to support the use of acupuncture as a single therapy for depression.

This is important: depression carries an appreciable mortality and morbidity and there are real ethical problems about withholding treatments that have been shown to work.

It also does not mean that acupuncture has no place in the treatment of depression: it may be a useful adjunctive treatment - particularly if the individual has comorbid anxiety - and it may help with treating the side effects of conventional medicines. There is also another important point: we need to be sure that we are measuring the right thing when doing studies on acupuncture: the Western doctor may want to see if depression gets better. The acupuncturist may be more interested in improving the overall well being of the individual as well as helping an individual’s search for meaning. 

Regular readers will remember that last month I commented on some promising research on the use of qigong in depression. Why the different results from the different studies? There are many schools of acupuncture, t’ai chi ch’uan and qigong, as there are many different medicines for depression. One of the difficulties in the critical evaluation of these forms of treatment is that we have to assess the effectiveness not just of acupuncture, but of different schools of acupuncture and sometimes of different practitioners: a daunting but not impossible task. Not only are there many school in China, there are also Japanese, Korean and Vietnamese variants of traditional acupuncture, Western acupuncture and electro- and laser acupuncture. We use clinical observations to guide us to research the most promising types of intervention, whether they are forms of acupuncture, herbal remedies, homeopathy or anything else.

My "job" is to bring you the best and most rigorous research so that you can make decisions about what is most likely to help you.

Blue Light at Night Morning Delight

                                 

Do you ever see that episode of the original Star Trek in which Spock is accidentally – and temporarily – blinded when he is exposed to ultra-bright light to drive out a parasite? For people who like to know such things, it was episode 29, entitled Operation: Annihilate!

In the end it turns out that he only needed to have been exposed to one invisible wavelength of light. Naturally enough, being Star Trek it all comes out all right in the end.

I was reminded of this as I examined some extraordinarily important recent research from Thomas Jefferson University in Philadelphia. We have known for a long time that light is an effective treatment for seasonal affective disorder (SAD). However, until now, nobody has been able to determine the best wavelength to use. This new research found that the most effective wavelength was blue. It is thought that blue light therapy may help a great many more things than SAD.

SAD is one of a group of disorders involving our circadian rhythms. Many experts are currently trying to establish the relationship between SAD and another major disturbance of circadian rhythms: bipolar disorder. They are certainly not the same thing, but they are closely related to each other. Some other circadian rhythm disturbances that may respond to blue light are sleep disturbances, jet lag, sleepiness during shift work and spaceflight.

It has always been assumed that the brain’s major pacemaker – the suprachiasmatic nucleus (SCN) – only responded to bright light at a certain time of day. The SCN regulates the production of melatonin by the pineal gland. The fact that lower-intensity blue light is more effective than the most visible kinds of light is part of a body of evidence that there is a separate photoreceptor system within the human eye. The system that resets the body clock to the 24-hour day is different from the rods and cones used in regular vision.

In linked research by the same investigators, as well as a team from and Brigham and Women’s Hospital and Harvard Medical School in Boston, blue light was shown to directly reduce sleepiness. People exposed to blue light were able to sustain a high level of alertness during the night when people usually feel most sleepy. The results suggest that light may be a powerful countermeasure for the negative effects of fatigue for people who work at night.

There is more to this research: breast cancer is linked to fluctuations in human circadian rhythms, with higher rates in industrialized countries where there is a great deal of exposure to artificial light at night. It has been suggested that melatonin may be a link between artificial light and breast cancer. Blue light may perhaps mitigate some of the effects of light on suppressing melatonin.

There is another point to be made here. Many people teach techniques of being able to see the human aura. Many of the techniques of the “See the aura in 30 seconds” type, are no more than visual illusions. But there is another group of techniques that involves the use of peripheral vision to gradually become aware of the fields around people, animals and plants. By a strange "conincidence" the ancients identified the pineal gland with the "third eye." Have the researchers inadvertently found a biological mechanism for seeing auras?

“Sleeplessness is a desert without vegetation or inhabitants.”
--Jessamyn West (American Writer, 1902-1984)

Exercise and Mood

Most people who exercise on a regular basis soon begin to notice that if they miss a day or two, it will quickly have an effect on their mood and motivation. There’s recently even been some research to confirm it. Many years ago it was shown that one of the mechanisms for the “Runner’s high,” was the production of endorphins and we now have a great deal of research that is revealing the fundamental mechanisms linking exercise and mood.

Though the link between exercise and mood has been recognized for decades, in the last few years we have seen an increasing body of evidence that exercise can have a useful effect on people with mood disorders. The evidence is extensive (For example: 1. 2. 3.) and is now so strong that many clinicians – and certainly all practitioners of Integrated Medicine – routinely recommend physical exercise as part of a package of health care. There is particularly good evidence that exercise will help with some of the less common types of depression. An exercise program may particularly benefit  women with progesterone-related premenstrual mood disturbances.

We now have some good evidence  about the mechanisms by which exercise can improve mood. Researchers in China did some experimental work in rats with what they called “Chronic unpredictable stress.” It is just what it sounds like. If the little critters keep getting stressed, they develop many of the signs of depression: they show loss of appetite, social withdrawal and a reduction in exploratory behavior. We could say that the repeated stress reduces their resilience. Chronic stress causes dysfunction in the hormonal system that links the hypothalamus and pituitary glands at the base of the brain, with the adrenal glands that are perched atop the kidneys.

The researchers then gave some of the rats the opportunity to exercise on a wheel. The exercising rats had an increase in the amount of a growth factor called brain-derived neurotrophic factor (BDNF) in a key region of the brain called the hippocampus. In the non-exercisers, the levels of the growth factor went down as they experienced more and more stress. Exercise also smoothed out stress-induced rises in the hormone cortisol.

This is particularly interesting because previous research had shown us that exercise can increase BDNF levels in the brains of stressed and unstressed animals. We also know that if an antidepressant is going to work, it has to be able to stimulate the production of BDNF in the hippocampus of the brain.

One thing that has not been much studied is the impact of exercise on sleep architecture. Most exercisers know that a good workout, run or hike can make you sleep like a log. And there is increasing evidence that correcting sleep disturbances can be a most effective way of improving mood. So much so that many of us now believe the sleep disturbances underlie many mood disorders, rather than sleep disturbances being symptoms of sleep disorder.

My conclusion from reading the literature and working with countless individuals is that unless there is a medical contraindication, a combination or weight training and aerobic exercise should be part of the treatment program for anyone with depression. The biggest problem is motivating someone with depression t do something like exercise. Sometimes it is necessary to wait until the primary treatment has taken hold. Though we have often had a great deal of success by using some of the motivational systems that I’ve described in Healing, Meaning and Purpose.

Qigong in the Treatment of Depression

I first started teaching T’ai Chi Ch’uan and qigong over 20 years ago, and I was always impressed by the apparent benefits for people with chronic low mood. Not so much in people with severe depression, but in people who were just chronically miserable.

During a visit to Hong Kong in 2004, I heard about some interesting research that’s just been published. Researchers from the Department of Rehabilitation Sciences at the Hong Kong Polytechnic University and Kwai Chung Hospital, examined the effects of regular qigong in 82 older people with a diagnosis of depression. After just eight weeks of regular daily practice, there was an overall improvement in mood, self-efficacy and personal well-being. By week sixteen there were really quite marked improvements not just in mood, but also in activities of daily living and how people felt about themselves.

We know that there are close links between mood and the immune system, so this research fits in with a study from Tokyo in which a breathing method said to enhance Qi was shown to reduce stress and modulate the function of the immune system.

There are many studies of qigong, but they are of variable quality. Another one which supports both of these two studies comes from Korea, where something slightly different - qigong therapy - was shown to help both pain and mood in older people with chronic pain form a variety of causes.

I do not think that we have enough evidence to try using qigong alone in the treatment of depression, which is, after all, a potentially fatal condition. But I do think that Qigong is an important part of an Integrated Medicine program, and I am creating more resources for people to do the first stages of qigong on their own.

Breathing

“Without mastering breathing, nothing can be mastered.”
--George Gurdjieff (Armenian-born Adept, Teacher and Writer, c.1873-1949)

I strongly recommend breathing. It’s actually one of my favorite pastimes….

Of course breathing is all-important, but it is just as important to ensure that you are breathing in good quality air. Scattered throughout the world are weather fronts accompanied by hot dry winds of ill repute:

• The Santa Ana Winds of Southern California,
• The Mistral of France
• The Khamsin of North Africa
• The Foehn of Switzerland
• The Sharav in Israel
• The Chinook of Canada
• The Sirocco in parts of the Mediterranean
• The Xlokk of Malta
• The Zonda in Argentina
• The Halny of the Carpathian Mountains

These are just some of these winds, that have been known for centuries to precipitate a variety of symptoms in the exposed population, including depression, irritability, insomnia and headaches. The explanation of these effects is an increase in the number of positive ions in the atmosphere, which alter the amount of serotonin in some parts of the brain. I was consulted about an epidemic of headaches amongst people working in an electrically insulated room. It soon became clear that the setup had allowed an enormous concentration of positive ions, and once they installed a negative ionizer virtually all the headaches stopped. We believe that many of the beneficial effects of high altitudes or of being near waterfalls of fountains spring from the way in which they generate large numbers of negative ions.

Poor oxygenation of the lungs has been known for many years to be associated with disease. Pulmonary tuberculosis classically affects the upper lobes of the lung, where there is the poorest oxygenation, and it has been known for a century that people suffering from a blockage of the mitral valve of the heart, which leads to high blood pressure in the lungs, do not get tuberculosis in that part of the lungs.

Conscious control of the breath enables us to modulate the activity of the autonomic nervous system. Specific types of breathing can induce specific psychological and physical effects.

We usually breathe through one nostril at a time. Either the right or left nostril is dominant for anywhere from 45 minutes to two hours. You then switch sides. This is known as the nasal cycle, and is one of the faster circadian rhythms. The popular yogic practice of single nostril breathing is thought to feedback directly into the hypothalamus of the brain. You can learn to use this to your advantage. If you are right handed, if you direct your focus onto opening the right nostril, you may well find an increase in salivation, which is an aid to good digestion. A useful trick that we have used for many years is at bedtime to start by lying on your left side, which has the effect of opening the right nostril, and after ten minutes roll onto your right side for sleep. Again you reverse this if you are left hand dominant. It seems that this simple trick lowers your core temperature, which is one of the main determinants of sleep. There is some research that opening the right nostril increases body temperature, while opening the left has a calming effect. These techniques are often very helpful. Apart from these physical effects, using the breath is one of the quickest ways to learn to sense the subtle forces of the body.

You may already have some breathing practice that you like, and by all means continue using it. If you need a new one, the simplest that I have ever been taught, and that I have used with countless students and patients is this:
Count your breaths. Breathe deeply using your abdominal muscles, so that you are drawing more air into your lungs. Stop immediately if you feel faint or dizzy. As thoughts come up, keep concentrating on the incoming and outgoing breath. Gradually slow the breath, by extending the pause between the inhalation and exhalation.

I always make myself unpopular when I insist that people check with a healthcare provider before stating any exercise plan, including breathing. But I'm going to say it anyway. It just makes good sense!

“Controlled deep breathing helps the body to transform the air we breathe into energy. The stream of energized air produced by properly executed and controlled deep breathing produces a current of inner energy which radiates throughout the entire body and can be channeled to the body areas that need it the most, on demand. It can be used to fuel a specific physical effort, such as tennis or jogging. Or you can use this current of inner energy to relieve muscular tension throughout the body, revitalize a tired mind, or soothe localized aches and pains.”
--Nancy Zi (American-born Chinese Opera Singer, Voice Teacher and Qigong Expert)

DHEA: Hype, Hope and Disappointment

Dehydroepiandrosterone (DHEA) is a hormone that has attracted a lot of attention. It’s launched hundreds of websites, product lines and a few books and magazine articles. So what’s all the fuss about, and should we all be chomping down on DHEA tablets?

DHEA is manufactured at several sites in the body, but by far the most important is in one of the outer layers of the adrenal gland. Like all the steroid hormones it is made from cholesterol. It has various protective effects in the body, regulates some enzyme systems, can be converted to estrogen and under certain circumstances to testosterone. It has very weak androgen (male hormone) activity.

In cell culture it has a lot of other actions too, but it is always difficult to jump from effects seen using large doses in isolated cells, to giving advice on what supplements people should be taking.

There has been a lot of talk about the possibility that some people may, as a result of stress or toxins, suffer from exhaustion of the adrenal glands. There is a great long list of symptoms that may be caused by this so-called adrenal fatigue, deficiency or insufficiency: the terms are often – and incorrectly – used interchangeably. And therein lies the problem. It is such a long list that it is non-specific. It’s always a bit of a worry when someone tells me that dozens of different symptoms are all caused by one single biochemical problem. That just isn’t the way that the human body works.

I have seen and treated countless people with a condition known as Addison’s disease: true chronic adrenal insufficiency. It can be a very serious illness and it is quite different from the “adrenal fatigue” that people talk about in some popular books. People with chronic fatigue syndrome do have lower levels of activity in what is known as the hypothalamic-pituitary-adrenal axis, but it is not because the adrenal glands are not working properly, but because the hypothalamus in the brain is not doing it’s job properly. There’s also no proven link between “burnout” and adrenal function.

During my years as an endocrinologist and holistic physician, I’ve spent a great deal of time looking for adrenal fatigue in sick people and I’ve never found it. I’ve done all the tests recommended by proponents of adrenal fatigue and adrenal insufficiency and when we’ve done the tests properly, we’ve drawn a blank. There are a great many parallels between the adrenal insufficiency story, and the old - and discredited - myth about people becoming unwell because of a thyroid deficiency that cannot be picked up on standard thyroid function tests.

So can DHEA do you any good? Or can it be harmful? What exactly is the evidence?

1. There is a comprehensive study, called The Dehydroepiandrosterone And WellNess (DAWN) study that should give us some solid answers as to the risks and benefits of DHEA. I shall post details of the findings as they become available. But some things we know already:
2. DHEA has been touted as an anti-aging supplement. But in a two-year prospective study done in older people attending the Mayo Clinic in Rochester, Minnesota, neither DHEA nor low-dose testosterone replacement had physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. Perhaps the people in the study didn’t get enough DHEA, but it doesn’t look that way. Instead it seems that just giving the supplement doesn’t seem to do very much. But there is increasing evidence that 50-100mg of DHEA each day will improve muscle strength and muscle mass in older people who are doing strength training. Once again, it does nothing in people who are not exercising. Sorry!
3. According to the results of a small placebo-controlled, randomized trial published in the Archives of General Psychiatry, DHEA can be effective for midlife-onset minor and major depression. The study was conducted the National Institute of Mental Health Midlife Outpatient Clinic. In the trial, 23 men and 23 women aged 45 to 65 years with midlife-onset major or minor depression were randomized to six weeks of DHEA therapy, 90 mg/day, for three weeks and 450 mg/day for three weeks or to six weeks of placebo followed by six weeks of the other treatment. The subjects did not receive any other antidepressant medications during the study. Both of the doses of DHEA helped improve depression: there was no advantage in going to a higher dose, and there was no difference in the treatment response of men and women. The trouble with this study was not just the small size and the short duration, but the DHEA was not compared against a standard antidepressant. So we are still in the dark as to how effective it really is. It’s nice that it’s better than placebo, but this is just the first step in a larger research program.
4. A study from Taiwan indicated that people with higher levels of DHEA sulfate had a lower overall mortality over a three-year period. That is interesting, but absolutely does NOT mean that artificially increasing our levels of DHEA with supplements will make us live forever: we don’t yet have that kind of magic bullet.
5. In mice, quite large amounts of DHEA have the effect of slightly reducing the normal increase in stiffness of the left ventricle that can happen as animals get older. We have no idea whether something similar might help in humans, and the amounts of DHEA involved may rule it out as a viable treatment in people.
6. 50mg/day improves subjective wellness in people who have no active pituitary gland. A rare condition, and we cannot use this evidence to advise healthy people about what to take.
7. Because DHEA is converted into estrogen and/or testosterone, it may have the potential to exacerbate or initiate hormone-responsive tumors. The evidence is not strong one way or the other, but it remains a worry. I don’t think that anyone recommends DHEA to people who have a personal or family history of breast or prostate cancer.

There is a BIG literature on DHEA. But my current conclusions from all this?

1. 50-100mg of DHEA is probably worth trying if you are over 50 years of age and doing regular exercise.
2. It may help a bit with mild depression.
3. It should not be used in people with a personal or family history of breast, prostate or any other type of hormone-sensitive cancer.

Pramipexole

Pramipexole is a remarkably interesting medicine about which you are likely to hear a lot in the near future. It is an agonist, which means that it has a positive effect, on D2 dopamine receptors and also on a little-known group of dopamine receptors, known as the D3 group. If you want to get really clever the dopamine receptor D3 group is abbreviated to DRD3. Pramipexole has been in use for almost a decade in the treatment of Parkinson's disease, and approximately 9.1 million prescriptions for pramipexole have been written in the U.S. since its launch in 1997. It is not without its problems. In Parkinson’s disease it may cause dizziness, involuntary movement, hallucinations, headache, difficulty falling asleep, sleepiness, and nausea. Some people have also had behavioral dyscontrol while taking it.

At a meeting in Athens in February of 2006, we saw confirmation of something that had been shown in previous research: pramipexole seems to be a very effective treatment for restless legs syndrome (RLS). A study published in the journal Neurology has given us a more detailed understanding of the risks and benefits of pramipexole.

The investigators report a 12-week, multicenter, double-blind, randomized, placebo-controlled study of fixed daily doses of pramipexole (0.25 mg, 0.50 mg, and 0.75 mg) involving 344 patients with moderate to severe RLS. Data from 339 patients were analyzed to evaluate the effect of pramipexole treatment on efficacy and safety. The mean age of patients was 51.4 years and the mean duration of RLS symptoms was 5.1 years. The results were very promising, even though half of the patients on placebo also showed an improvement. The most commonly reported side effect included nausea (19.0%), headache (17.8%), insomnia (10.5%) and somnolence (10.1%).

In Europe pramipexole it has been approved for use in this indication. It is marketed as Sifrol® / Mirapexin® In the United States we currently only have one approved medical treatment for RLS, and that is the GlaxoSmithKline medicine ropinirole (Requip), that works at the same D3 receptors in the brain and spinal cord. Ropinirole is effective in a proportion of people with RLS, but it has also been linked to sleepiness, drops in blood pressure and fainting, so those are included in its label.

RLS may be associated with some other illnesses so I was very interested to see two reports of the use of pramipexole in bipolar depression as well as a report of its possible use in REM Behavior Sleep Disorder.

One of the most exciting potential uses for pramipexole may be in some people with fibromyalgia. I’ve mentioned that fibromyalgia, bipolar disorder and some other psychiatric illnesses may be connected. The idea that we might be able to use just one medicine to support our Integrated Medicine approach is very attractive, and also helps point us toward a deeper understanding of what exactly goes wrong at the physical level in RLS, depression and fibromyalgia.

I’ll keep you posted.

Retinoic Acid and Suicide

Retinoic acid is an organic compound derived from Vitamin A, that is involved in the development of the brain and in normal visual function. It is because of the involvement in the formation of the brain that medicine containing retinoic acid like compounds must not be given to women who could become pregnant.

In recent years it has become clear that it is also involved in the function of the mature nervous system, and there have been suggestions that it may have a role in illnesses life Alzheimer's disease and schizophrenia.

One of the big breakthroughs in skin care was the introduction, in 1982, of a form of retinoic acid - isoretinoin - for the treatment of severe acne. It is marketed as Accutane in the USA and Roaccutane in the United Kingdom. Since its introduction there have been claims that it has caused depression and suicide in some patients taking it. The package insert specifically mentions this possible association. The trouble has been trying to sort out whether people taking it for acne became depressed because of the acne, whether it was the drug, or whether it was a chance association. 13 million patients have taken it world-wide, so sadly some depression might occur by chance.

That it was the drug causing the problem was supported by reports of people developing depression within days of starting the medicine. But it's always difficult to go from association to causality. After all, it has not been possible to prove that smoking causes lung cancer, though nobody doubts it, becuase the association between the two is so strong.

The Medicines and Healthcare products Regulatory Agency had received 1,588 reports of suspected adverse events experienced by people taking the drug up to this month. This included 25 people who died from suicide.

Now a paper in the journal Neuropsychopharmacology has added substantial support the the notion that the medicine may cause depression. The researchers gave a form of retinoic acid to adolescent mice. They found that while there was no change in the physical abilities of the mice, the rodents spent significantly more time immobile in a range of laboratory assessments designed to test their response to stress.

This was interpreted as a sign that the animals were exhibiting signs of depression.

It's difficult to extrapolate from mice to humans, and this certainly does not nail down the problem. It also does not mean that people should stop their treatment: this medicine works. But it emphasizes the importance of doing what the package insert says: watching young people with acne who are on treatment for any signs of depression.

Psychiatric Illnesses and Fibromyalgia

There’s an interesting and important article in last month’s issue of the Journal of Clinical Psychiatry, by a group of investigators from the University of Cincinnati.

They have shed important new light on fibromyalgia. We’ve recently learned how it is linked to disturbances of the serotonin transporter, as well as anti-inflammatory proteins, and that is may respond best to the kind of comprehensive multi-leveled approaches that we use in Integrated Medicine.

The new research compared people with fibromyalgia with people with rheumatoid arthritis, and it found that fibromyalgia, but not rheumatoid, may be associated with a range of psychiatric illnesses:

1. Major depressive disorder
2. Bipolar disorder
3. Comorbid anxiety disorders including panic disorder, social phobia, posttraumatic stress disorder and obsessive-compulsive disorder
4. Eating disorders and
5. Substance abuse

What was particularly important in this study was that the psychiatric problems usually preceded the onset of fibromyalgia. So it wasn’t that people were developing psychological problems because they were in chronic pain.

It’s beginning to look as if fibromyalgia is part of a larger group of disorders that all share common etiologies or causes. Family studies have indicated that fibromyalgia and mood disorders share some of the same - perhaps genetic - determinants.

The study also confirms what we have said before: fibromyalgia is not only associated with some psychiatric problems, but also with other medical disorders, several of which may also co-exist with the same psychiatric problems. They include:

1. Chronic fatigue syndrome
2. Irritable bowel syndrome
3. Interstitial cystitis
4. Multiple chemical sensitivities and
5. Migraine

Not only does this research highlight the need to check people with fibromyalgia to see if they might also be struggling with a psychiatric problem, but it is helping us home in on some of the mechanisms linking these apparently separate problems.

This particular study was done mainly in white women, and the investigators knew who had fibromyalgia, so there’s more work to be done.

But if you or a loved one is struggling with fibromyalgia, it is good news to know that we are making rapid progress in unraveling this horrible illness.

Artificial Light and the Biological Clock

Many of the things that we do to babies and young children have been called into question in recent years.

The debate about doing an excessive number of fetal ultrasounds and high tone deafness seems to have gone away for now. Though not disappeared: there is a paper in the week's Proceedings of the National Academy of Sciences that revisits this important issue. Then there was the realization that doctors were not good at recognizing and dealing with pain in very young children.

And now there is another one that has worried me for years: what happens to babies who are exposed to constant high levels of light? Doesn't it damage the development of normal circadian rhythms?

I have just seen a study that seems to confirm some of those fears.

Investigators from Vanderbilt University in Nashville examined the impact of exposing babt mice to constant light. The main biological clock is in the brain, and is located in a region called  the suprachiasmatic nuclei (SCN). It is responsible for orchestrating an orderly internal physiological and behavioral cycle. It influences the activity of virtually all our organs, including the brain, heart, liver and lungs. It egulates the daily activity cycles that we call circadian rhythms.

When the mice are exposed to normal variations in light the cells of the SCN quickly become synchronized, and a normal circadian rhythm is established. Constant exposure to light disrupted the development of the SCN and prevented the animals from developing normal circadian rhythms.

This is far from being an academic exercise: each year around 14 million premature babies are born worldwide, and many are exposed to artificial lighting in hospitals. If their biological clocks are not allowed to develop normally, we would anticipate that they would, in later life, have less psychological resilience, and to be prediposed to sleep and mood disorders.

I could conceive of a way to test that experimentally by looking at records of people wth those problems. Secondly, we need to see if reducing unnecessary light exposure would have a real benefit for babies, and for the children and audlts that they will become. I would be astonished if exposing babies to a natural spectrum of light and a natural light cycle did  not have enormous benefits for them as they grow up.

Friendship and Psychological Distress

“To lose a friend is the greatest of all losses.”
Publilius Syrus (Syrian-born Latin Writer, 1st Century B.C.E.)

Severe and persistent mental illnesses are one thing, but there are many, many more people who are miserable and unhappy, without that unhappiness necessarily getting to the level of an “illness.” The offices of primary care physicians and therapists are full of people in genuine distress for all kinds of reasons.

I first began to think about this many years ago when a woman came to see me and promptly announced, “I’ve come for psychotherapy. I’ve been in therapy for seventeen years, and I want some more.” I wasn’t being in the slightest bit flippant when I responded by asking her if, after seventeen years, she really felt that it had offered her anything? She looked at me blankly, and it soon became very clear that what she needed was not more therapy, but a friend to talk to.

There has been another puzzle: why is it that women are more likely to develop depression than men? The most profound gender difference in mood disorders begins to emerge after puberty, so it would be easy to attribute it all to hormones. But that would be a mistake.

I recently pointed out that there are some fundamental differences in the ways in which men and women interact: women tending to be more relational and men tending to be more transactional. The female sense of self tends to be more entangled with her relationships, while a man’s self-worth and sense of self is more often associated with his achievements. Most of these differences begin to emerge in early puberty: when girls talk to their friends, their conversation tends to be more emotional and to be concerned primarily with relationships, while boys tend to be more reserved and to discuss facts, statistics and achievements. There is some evidence from research in different cultures that these different styles seem to be the norm throughout the world. Yes, there are of course plenty of people of both genders who behave differently, and so it is more accurate to relate these differences to the male and female factor or essence, rather than getting it confused with anatomical differences.

Emotional language tends to put more strain on a relationship, and it is well-recognized that girls’ relationships turn over much more rapidly than boys’ ones. An interesting hypothesis proposed some years ago by Professor Sir David Goldberg, is that this high turnover in relationships may lead girls to experience more disappointing experiences in their social networks, and it is this string of disappointments that predisposes young women to depression.

A happy, healthy, dynamic network of friends is a cornerstone of developing and maintaining psychological resilience. Without them you become progressively more vulnerable to the reversals that affect all of us from time to time.

“A friend might well be reckoned the masterpiece of nature.”
--Ralph Waldo Emerson (American Poet and Essayist, 1803-1882)

“To know how to live in a brotherly way with those around us is to be rich, for each of us, with our face, eyes, voice and thoughts, contributes something alive, something warm, which nourishes everyone.”
Omraam Mikhaël Aïvanhov (Bulgarian Spiritual Master, 1900-1986)

Irritable Bowel Syndrome, Mood Disorders, the Serotonin Transporter and Integrated Medicine

Whenever we run into two common conditions, it’s easy to imagine links where none really exists. Three years ago some colleagues from Oxford reported on a person with bipolar disorder and irritable bowel syndrome, and commented that the association was uncommon.

However there may after all be a genuine link between mood disorders and irritable bowel syndrome, that is a disturbance in the “third arm” of the autonomic nervous system. The first arm is the sympathetic nervous system, the second the parasympathetic and the third is the enteric or gut nervous system that is closely linked with key regions of the brain.

Not long ago there was an interesting report of a woman who had multiple problems including environmental allergies, atypical bipolar disorder, irritable bowel syndrome and Raynaud’s phenomenon. Such odd constellations of problems are quite familiar to anyone working in the major referral centers around the world, and some can be exceedingly hard to treat. Tough cases like this often stimulate further research. I once tried and failed to treat a woman with a chronic illness. When she came back a year later to see if I had any new ideas, I told her that I now had a shelf of books and over a thousand reprint of papers about her condition: I don’t like failing someone. And I’m not unique in that.

A new study from the Karolinska Institute in Stockholm, has found that chronic widespread pain, which, as I explained recently, is the cardinal symptom of fibromyalgia, is prevalent and co-occurs with other symptom-based conditions such as chronic fatigue syndrome, joint pain, headache, irritable bowel syndrome, and psychiatric disorders. There is more and more evidence of a link between fibromyalgia, irritable bowel syndrome and depression. It is not just that people are sick and get depressed: as we shall see in a moment, the link is more subtle than that. Another illness seemingly linked to these three is interstitial cystitis.

Now some colleagues at the National Institutes of Health have been looking at a serotonin transporter (SERT) that regulates the entire serotoninergic system and its receptors. This transporter is found throughout the animal kingdom, telling us that it must be important.

In humans the gene is located on chromosome 17, and disturbances in it have been found in people with autism, ADHD, Tourette’s syndrome and bipolar disorder. Experiments using genetic engineering suggest that SERT may be a candidate gene for several human disorders, from obesity to irritable bowel syndrome. People who have disturbances in SERT tend not to respond so well to the serotonin reuptake inhibitors (SSRI’s) antidepressant medicines.

SERT is not the whole story. Some geneticists from Los Angeles have found evidence linking irritable bowel syndrome, depression, migraine and inheritance of mitochondrial DNA.

Many approaches have been tried to help people with these groups of problems. I always find it remarkable that psychological treatments can be so effective in conditions with a genetic component, for this once again proves that biology is not destiny.

The best approaches to conditions like irritable bowel syndrome and coexisting mood disorders is to use medications and psychological approaches. Many of us have also found that the addition of nutritional, environmental and subtle energetic approaches have been of great help, together with some work to uncover the meaning and transpersonal value of a chronic illness. That last piece is not the first priority, which is to help the person gain control of his or her life. But if we don’t do something to work with the meaning and purpose of an illness, it will usually come back in some form or other. This comprehensive approach differentiates Integrated Medicine from many other types of therapy.

Social Supports, Sense of Coherence and Recovering from Depression

After writing about the importance of trying to establish a personal sense of coherence, I was just able to look at an important piece of research.

The authors are from Sweden, a country in which, from my experience, there is still a great deal of social cohesion, despite all the experiments that have been going on there in recent years.

So unlike countries in which there are terrible social supports for everyone, they had the opportunity to study the good and the bad.

Though only a small study, the conclusions are unsurprising but important. They were looking at people with a first episode of major depression, and 71% of the patients had recovered at follow up.

The sense of coherence scores were low at baseline, although the patients who recovered significantly increased their sense of coherence. Another factor of importance for recovery was a significant increase in social support.

It is intuitively obvious that social support is an important part of the restoration of a person's sense of coherence. It can be used in interventions that include the patient's family or close social network in combination with support to assist the patient to view his/her situation as comprehensible, manageable, and meaningful, thereby promoting or improving health.

The bottom line: professionals need to identify people's strengths and weaknesses so that the support and interventions provided can be tailored to meet the needs of each individual.

And one of the best ways of staying healthy is to maintain your social supports, to provide them for other people, and to work on increasing your own sense of coherence.

Toxoplasmosis, Behavior and Mental Illness

This title may seem odd, but this item may actually turn out to have enormous implications for all of us.

A couple of years ago I read a fascinating book: Parasites and the Behavior of Animals, in which the author – Janice Moore from Colorado State University – cataloged some of the extraordinary ways in which parasites can impact the behaviors of a vast array of animals. As difficult as it is to interpret studies of parasites in humans, I kept coming back to some odd observations about an illness with which I’ve been involved for more than 30 years: schizophrenia. I kept wondering if some of the odd observations made over the years could be explained by the parasites?

What kind of odd observations?

1. Reports of mental illness have been found throughout history, yet this strange illness that we now call schizophrenia seems to have been very rare until about 1750, when it increased dramatically throughout Western Europe. I have had the privilege of working at the Bethlem Royal Hospital from which got the word “bedlam.” I know of the incredible records kept there. Something began to change in some of the types of patients being admitted at that time. I have also had the opportunity to look at some of the records at the Philip’s Hospital in Southern Germany, which has been in existence since 1533. Again the records show the sudden appearance of many cases of something that had been quite rare until then. 1750 marked the early years of the industrial revolution in Europe and the mass migration of people from the countryside to the new and very crowded cities
2. There has been recent evidence that being born and raised in a city increases your chance of developing schizophrenia.
3. There is increasing evidence that acute episodes of psychosis, mania and depression are associated with increases in circulating inflammatory mediators. There is also intriguing new data that both psychosis and depression can be improved by giving people COX2 inhibitors.
4. There has also been the strange observation that bipolar disorder may have been becoming more common in recent years, over and above our greater ability to recognize the illness.

Several years ago the well-known psychiatrist E. Fuller Torrey first suggested that a small protozoal parasite called Toxoplasma gondii might be responsible for all of these observations. Cats can carry it, which is why pregnant mothers are advised not to pet their cats during pregnancy.

The idea that such a complex disease as schizophrenia might sometimes be caused by a parasite caught the media’s attention, but in recent years the story – but not the ongoing research – died down a bit.

There was an excellent and provocative blog item by Carl Zimmer about this almost three weeks ago, but I wanted to check everything out before responding. He gave a brief review of a new paper published in the Proceedings of the Royal Society, by Kevin Lafferty from the University of California in Santa Barbara. Lafferty has attempted to correlate the varying rates of Toxoplasma in different countries with predominant personality traits and therefore – since our societies are aggregates of all our personalities, cultural characteristics.

That may all sound far-fetched, but I don’t think that it is. And I don’t think that the Proceedings would have taken a completely half-baked proposition.

I have also found a report published in the journal the Proceedings of the Biological Society. Four eminent authors, including Torrey, revisited the while issue of Toxoplasmosis and mental illness. When the parasite gets into the nervous system it can alter behavior: Rats are normally programmed to avoid cats, but once infected they are attracted to cats. Over the last few days I’ve been plowing the world literature, and I’ve learned some very interesting things that support the idea that Toxoplasma may be playing a role in several different types of psychiatric illness.

There is strong evidence that schizophrenia, bipolar disorder and major depressive disorder lie on a spectrum. The illnesses are not the same, but people often switch from one type of clinical presentation to another. The precise type if illness would be determined by the interaction of genes, physical and Intrapsychic environment. Nobody would be sufficiently naïve to try and reduce the whole of psychiatric illness to a single bug. Mental illness is a great deal more than just a physical problem, and apart from anything else, the rates of Toxoplasma infections show remarkable variations around the globe, while the rates of major mental illness are much the same everywhere.

So what have I learned?

1. There are a remarkable numbers of studies showing that many people with schizophrenia have antibodies to Toxoplasma, including people having their first attack of the illness
2. Blood donors infected with Toxoplasma have decreased levels of novelty-seeking
3. In women who become infected, there are some marked changes in personality.
4. Toxoplasma affects the dopamine systems of the brain that we know are intimately involved in mood, cognition, movement and motivation.
5. Some drugs used to treat psychosis (haloperidol) and mood disorder (valproic acid) inhibit the replication of Toxoplasma gondii. The valproic acid already does it at concentrations lower than we normally aim for when treating humans.
6. There is some intriguing work going on into the use of antibiotics to kill Toxoplasma and reverse its behavioral effects.

In the last few years, so many illnesses have turned out to have infectious origins, from peptic ulcers to arteriosclerosis and some cancers. Perhaps some mental illnesses will be next.

Last year Barry Marshall and Robin Warren were awarded the Nobel Prize in Physiology or Medicine for their pioneering work on Helicobacter. I have a strong sense that there are more prizes to come on the interaction between infectious agents, inflammation, genes, the psyche and the environment.

Perhaps the reason that some antipsychotics and mood stablizers can reverse some of the neurological damage associated with schizophrenia and bipolar disorder is becuase they are killing off the causative agents and allowing the brain to repair itself.

I shall keep you posted!

There's More to Weight Than Meets the Eye

There's an interesting article about the associations between obesity and mental illness.

We've all become so used to people telling us about the physical consequences of carrying extra weight, so it is interesting to learn that obesity may also be associated with higher rates of mental illness. We have here a typical chicken and egg problem.

Do people become depressed because they are overweight, or does depression and its treatments cause obesity? The answer is probably "Yes." It is both.

Depression may cause insulin resistance and hypercortisolemia, which may result in weight gain. But insulin resistance alters the kinetics of some of the amino acids that are the building blocks of key neurotransmitters in the brain.

And this study re-emphasizes the importance of treating the physical, psychological, social, subtle and spiritual aspects of a problem simultaneously. If we address only one of these dimensions, people will continue to suffer needlessly.

When our clinicians see overweight people with depression or bipolar disorder, they start by treating the mood disorder, but then immediately get to work on the weight problem. And all of it is part of the five vector, or five dimensional approach to treatment: physical, psychological, social, subtle and spiritual.

If we fail to respect and work with every aspect of a person, each problem will return to make us respond appropriately.

After all, illnesses are like any other problem: sent to educate us. Not just you, but also the person to whom you went for help.

Temperament, Depression, Class and Resilience

Within the first few weeks of life, infants show marked individual differences in their level of activity, their responsiveness to change in the environment and their irritability. Some clearly enjoy being touched and mold their bodies to the person holding them, while other stiffen and squirm and do less to adjust their bodies to another person. These mood-related personality characteristics are called temperaments. There is some evidence that temperament is one of the basic building blocks of the personality. Temperament appears to consist of inborn traits, but they can be modified by parental contact: there is actually a reciprocal relationship between child and parent. The child modifies the behavior and attitude of the parent.

It is commonly said that a child’s temperament is as fixed as handedness or eye color, but this is inaccurate: we have overwhelming evidence that temperament can be changed by environmental influences. This makes sense. In Healing, Meaning and Purpose, we discuss the implications of the new findings about genes in the brain: they do not so much determine behavior as predispose you to the way that you will handle the environment. An important questions is just how plastic is human temperament? To what extent can you overcome your genetic programming and early rearing? Some recent research has indicated that the environment of the first three years of life is not as critical to later development as we used to believe. But I think that it’s dangerous to read too much into this research. Early emotional deprivation may leave the deepest scars and also be associated with physical deprivation. If a developing brain is deprived of key nutrients, it is difficult to catch up later.

More and more research is finding key genes that contribute to temperament. There is important evidence from animal research that the temperament of infant female rats can predict life span in those who develop spontaneous tumors. It is difficult to extrapolate from that to humans, but it is a further demonstration of the incredibly subtle interactions between genes, the environment, behavior and physical illness.

Some important recent research has examined the impact of temperament on the clinical features of bipolar disorder and of ADHD and autistic spectrum disorders. As expected, people with ADHD reported high levels of novelty seeking and high levels of harm avoidance. Patients with autism spectrum disorders were low on measures of novelty seeking, they had little dependence on rewards and high harm avoidance. Cluster B personality disorders, the dramatic, emotional, or erratic disorders ones (antisocial, borderline, narcissistic and histrionic), were more common in people with ADHD and the other clusters A and C were more common in autistic spectrum disorders. This tells us that these tow clinical conditions can have some specific effects on the structure of temperament, and on the risk of developing specific personality disorders.

In a new study in next month’s issue of the Journal of Personality, Kati Heinonen and colleagues from the Department of Psychology at University of Helsinki, have found a correlation between adult pessimism and childhood temperament in low socioeconomic status (SES) families. It is no surprise to learn that children raised in higher socioeconomic groups have a more optimistic outlook on life. But this is what is interesting, and the thing that will launch a great many more studies. It was discovered that the effect of childhood socioeconomic status on pessimism tended to remain the same despite opportunities for socioeconomic fluidity. A person from a low SES childhood who moved upwards in status was less likely to be optimistic as an adult than someone from a high SES childhood who remained in a high SES environment. The inverse also held true, as people from a high SES childhood who moved downwards in socioeconomic status were more optimistic than those who remained in low SES. This indicates that children who had the chance to develop coping strategies during childhood and subsequently developed a sense of mastery and control that protected them in adulthood from the adverse effects of lower SES. By contrast children from lower SES backgrounds who are subsequently upwardly mobile may not have had the opportunities to develop those psychological resources. They are thus unable to benefit as much as possible from later experiences of success.

We already know that pessimism is related to physical and mental health, so this new study provides a critical link between socioeconomic status and long-term outcome. This is essential information for policy makers and for parents interested in helping children develop more effective coping strategies.

This research really proves that some of the excessive optimism of the self-help movement can sometimes be misplaced: just wanting something to be different does not make it so. If you had a lousy up-bringing in impoverished surroundings, it will make it more difficult to bounce back and learn essential coping skills.

More difficult, but not impossible.

Research on resilience has provided us with a great deal of information about developing mastery and coping skills in the face of being in a low SES, and we shall return to some of that work in the near future.

Technorati tags: Temperament Socioeconomic status Resilience Depression Attention deficit hyperactivity disorder Autistic spectrum disorders Personality disorders

Stress, Depression and Resilience

“Patience in calamity, mercy in greatness, fortitude in adversity; these are the self-attained perfections of great saints.”
--The Hitopodesa (Sanskrit fable from the Panchatantra, the “Five Chapters,” Translated as the “Good Advice” c.1100 A.D.)

We are all different in the way that we respond to emotional and physical stress. It is not enough to focus on one single reason why one person handles it and another does not. I have often made the point that we need to consider the physical, psychological, social, subtle and spiritual contributions to any illness or challenge.

New research is shedding light on the interaction between two of these: genes and environment. A multinational research effort assessed the impact of stressor on mood in 275 pairs of female twins. 170 sets of twins were identical: they have exactly the same genetic makeup.

The research indicates that only 12% of individual differences in reactions to stress can be attributed to genetic influences. This is stunning, and should have been reported far more widely: 88% of the differences in the way a person reacts to stress are not genetic, but personal and environmental. This is of great importance in problems such as depression. If genetic factors play such a small role, then paying attention to the development of personal resilience - as well as dealing with social factors – is more likely to be effective than anything else. And, as has been discussed elsewhere one of the ways in which some medicines help people with depression, bipolar disorder and schizophrenia is probably by increasing their resilience.

I have already started showing you some of the techniques for improving psychological resilience and in a future publication we are also going to start work on physical, subtle and spiritual resilience and how to develop more resilient and dynamic relationships.

"Never allow anyone to rain on your parade and thus cast a pall of gloom and defeat on the entire day. Remember that no talent, no self-denial, no brains, no character, are required to set up in the faultfinding business. Nothing external can have any power over you unless you permit it. Your time is too precious to be sacrificed in wasted days combating the menial forces of hate, jealously, and envy. Guard your fragile life carefully. Only God can shape a flower, but any foolish child can pull it to pieces."
--Og Mandino (American Motivational Speaker and Author, 1923-1996)

Technorati tags: Resilience Depression Stress Environment Genetics

Revisiting Resilience

“I don't measure a man's success by how high he climbs, but how high he bounces when he hits bottom.”
--General George S. Patton (American General, 1885-1945)

Resilience is the process of being able to adapt and to thrive in the face of adversity, stress, trauma, tragedy or threats. A resilient person is les likely to succumb to any of these life events and is less likely to develop mental illness. But resilience is more than a passive strength or resistance to the slings and arrows of outrageous fortune: it is a dynamic capacity that not only protects us, but enables us to turn adversity into strength and an opportunity for growth.

Despite our extraordinary health care system and a multi-billion dollar antidepressant industry, the rates of depression are increasing throughout the Western world. A recent book has suggested that boredom was unknown before about 1760: the beginning of the Industrial Revolution. All this tells us that something is seriously wrong with our resilience.

“The measure of a man is the way he bears up under misfortune.”
--Plutarch (Greek Biographer and Priest to the Oracle at Delphi, A.D. 46-c.120)

In Healing, Meaning and Purpose, I pointed out some of the incredible changes that have taken place over the last one hundred years, and their impact on health. To try and apply the principles of the past to the problems of the present and future is unlikely to be crowned with success. We need to adapt. Buddhists do not normally eat meat. Except for Tibetan Buddhists, who need to eat some meat in order to survive at the high altitudes of the Himalayas. I have a good friend who created the finest integrated medicine clinic in the world, the Hale Clinic in London. Normally an abstemious vegetarian, when she was embroiled in business meetings, she would often take some meat to remain grounded. I have done the same thing myself for years. I prefer not to eat meat. I have not had a steak in more than thirty years. But if I am to do a lot of traveling and need to work with politicians and business people, a bit of chopped up fish or poultry can be essential.

The changes in our lifestyles over the past century have dramatically reduced the level of physical activity necessary to provide life's basic resources: our effort-based rewards that are intimately involved in the regulation of mood. If you think about it for a moment, if your great-grandparents wanted to eat, there was probably a lot of effort involved. Our brains still contain a huge number of circuits that evolved to play roles in sustaining the kind of continuous effort that would be critical for the acquisition of resources such as food, water and shelter. So what happens when we suddenly on longer need much physical activity to obtain those resources? What happens to those parts of the brain that have millions of years evolving? There will be reduced activation of those brain regions essential for reward, pleasure, salience, motivation, problem-solving, and effective coping strategies. The practical consequence of that is that these systems will not sit there idling: if under-stimulated, since these systems are so heavily involved with our emotions, we would expect to see people becoming depressed. And we know that depression has been increasing throughout the Western world. Of course, many people need to stimulate these regions of the brain artificially, as with drugs, pornography or extreme sports.

Effort-based rewards are an essential component of resilience to life's stressful challenges. Purposeful physical activity is important in the maintenance of mental health. It therefore makes sense to put more emphasis on preventative behavioral and cognitive life strategies, rather than relying solely on psychopharmacological strategies. Our strategy is geared toward protecting people from developing depression, and compensatory behaviors. One of the very interesting new ideas in pharmacology is that antidepressants and antipsychotics may act to enhance resilience at both the cellular level and in the whole person. This is a very different concept from thinking of medicines as chemicals that simply block symptoms.

Our aim is to improve resilience and gradually to increase activation of all those under-used systems of the brain to treat and then to prevent problems. All the things that mother always said were good for you: healthy exercise, meditation, a balanced diet, charity and kindness, and actions aimed at fulfilling your personal and Higher Purpose have already been shown to treat and to protect.

Here are some proven methods for improving resilience:
1.    Learn to be adaptable: the heart of resilience is the ability to take things in your stride and to be able to surf the ocean of change, rather than trying to hold the hold it back.

2.    Be aware of the blockages in your mind or in the subtle systems of your body that are preventing you from bouncing back form adversity

3.    Attitude: avoid seeing a challenge as an insurmountable problem

4.    Accept that change is part of life: you can do little about it, but you can do a great deal about how you react to change

5.    Ensure that you have meaningful goals that are consistent with your core desires and beliefs, and that you are moving toward them

6.    Do all that you can to work on establishing your own Purpose in life. You can create a purpose for your life, but also be aware that there is a Higher Purpose in you life

7.    Take decisive actions: even if the first action may not be the best one. Any action is usually better than denying that problems exist, and hoping that they will evaporate while you are asleep or watching television

8.    Develop and maintain close relationships. Even if you are not a sociable person, relationships are one of the most potent way of protecting yourself from life’s ups and downs

9.    Look for opportunities to learn more about yourself, and how you react to situations. This doesn’t mean becoming an introvert or a rampant narcissist, but it does mean taking a moment each day to review where you are and what you can learn form things that are or have happened in your life. This is a big subject, but there are many good ways to answer the question, “Why is this happening to me  again?” and from preventing habitual problems and routine self-sabotage. (I shall be publishing an eBook and CD about this crucial topic in the very near future)

10.  Work on developing a positive self-image. I have had some harsh things to say about the excesses of the self-esteem movement, but it has now been replaced by something far more valuable: the science of positive psychology. We have a great deal of empirical data on how to improve a person’s happiness and resilience. Again, we can speak about that some more if you are interested.

11.  Maintain hope for the future. We have done research that has shown that one of the best ways of predicting a positive outcome with major mental illness, or of reducing the risk of recurrent substance abuse is to instill hope. Again, there are techniques for doing this, even when the whole world seems to be against you.

12.  Maintain perspective: do not blow things out of proportion, and remember that this too shall pass.

13.  Take care of yourself, physical, emotionally and spiritually. Listen to yourself: what does your body need? What do you need emotionally? What do you need from a relationship? What do you need spiritually?

14.  Are you giving others what they need from you? If you have a nagging sense that you are not giving a child or a spouse that they need and deserve, it can dramatically reduce you resilience.

15.  Rather than just thinking about and worrying over your problems, or problems that may turn up in the future, get into the habit of thinking of yourself not just as an individual who is going through problems, but as a boundless spiritual being who is learning a lesson.

16.  Never forget to think about the legacy that you are going to leave. Not just to your family, but to the world at large. If you can’t think of one, this is a good time to begin to create one. That is an enormously  powerful perspective on the world and on your problems.

“I am an old man and have had m