Richard G. Petty, MD

Rhythms in the Brain

It is often a bit frustrating to read articles about the brain in which the writer says things like: “research has shown that the insula does this…” or “the amygdala does that…”

This idea that it is possible to reduce brain functions to regions of the brain is not correct. Some years ago I used the term “Neo-phrenology,” to describe this fallacy, though I am sure that I was not the first. (Phrenology was the old and discredited theory that you tell things about people by examining the bumps on their heads.)

So why is it a fallacy? The idea that certain functions can be “localized” to a bit of the brain is called “naïve localizationism.” The vast majority of the psychological functions of the brain are performed by distributed networks, not a single lump of tissue. One of the remarkable things about the human brain is that it can recruit new circuits as they are need. If we do not have enough brainpower to solve a problem, other systems are taken off line so that they do not distract and may be able to help. You have probably had the experience of working on something so intensely that you lose track of time, and fail to hear things going on around you.

Yes, there are regions that have jobs to do. For instance the auditory cortex is responsible for processing sound. But after that initial processing the rest of the brain becomes involved in deciding what to do with the information. The key to understanding the brain is how different regions of the brain communicate. As I recently mentioned in a different context, there are good reasons for believing that a number of problems, from the schizophrenias to the attention deficit disorders, may all be a result of poor communication between different regions of the brain.

Part of the problem is working out how regions communicate has been technical: we have not had the computers or hardware to do the measurements. But that is beginning to change.

Earl Miller, a professor of neuroscience at Massachusetts Institute of Technology's Picower Institute for Learning and Memory, recently said that today's faster computers and more advanced electronics might provide scientists with the tools they need to unlock the brain's mysteries.

"Multiple electrode recording techniques, offer a whole new level of brain interactions that can't be seen using the [current] piecemeal approach."

Two studies published recently in th journal Science support this idea.

In the first Thilo Womelsdorf and a group of neuroscientists at the F. C. Donders Center for Cognitive Neuroimaging at Radboud University Nijmegen in the Netherlands, looked at the electrical activities of groups of neurons in the brains of cats and monkeys wile they were engaged in an array of different tasks. They found that two groups of neurons could only communicate efficiently with each other when their rhythms are coordinated, or synchronized.  If the rhythms are not coordinated, then one group sends information while the other is not ready to take it on and vice versa.

The researchers found that when the rhythms of electrical activity are synchronized between neurons in distinct brain areas, memories are made and tasks are completed more efficiently.

The other study, by scientists at the University of Melbourne in Australia, also revealed communication between the cerebral cortex and the deep medial temporal region.

They flashed two images at a group of macaque monkeys for less than a second. The monkeys had to decide whether the spatial orientation of a stack of bars in two images were the same or different. While the animals worked, researchers monitored the electrical fields in the posterior parietal cortex, which is one part of the system involved in directing spatial attention. At the same time they looked at the medial temporal area, a region deep in the midbrain that handles movement perception. The researchers had hypothesized that these two areas need to communicate with one another to enable reasoning.

The researchers observed activity first in the parietal cortex, followed by synchronous action there and in the medial temporal area. The delay illustrates "a top-down" feedback from the cortex, which then signals the lower area.

One of the authors, Trichur Vidyasagar, said,

“The parietal neurons seem to code for what is salient or relevant in the world and allocate attentional resources accordingly. The medial temporal neurons are sensory ones that process the visual signals, but due to the influence of the parietal cortex the activity across the medial temporal area is varied."

The studies were accompanied by an editorial in which Robert Knight, a cognitive neuroscientist at the University of California, Berkeley, praised the findings - and their potential significance.

This research is important for two reasons:
First it confirms that the key to understanding the brain is the interaction of networks.

Second, there are a number of periodic disorders, such as depression, seasonal affective disorder, mania and even some rare types of episodic psychosis that are episodic and are not associated with any clearly defined neuroanatomical disruption. It may well be that some of the periodic symptoms are caused by intermittent network dysfunction, as a result of disturbed oscillatory dynamics.

“In all things there is a law of cycles.”
--Publius Cornelius Tacitus (Roman Historian, Writer, Orator and Public Official, A.D.56-c.120)

“Human beings, vegetables or cosmic dust, we all dance to the same mysterious tune, intoned in the distance by an invisible player.”
--Albert Einstein (German-born American Physicist and, in 1921, Winner of the Nobel Prize in Physics, 1879-1955)

“It has been said that a complete understanding of the Law of Cycles would bring man to a high degree of initiation. This Law of Periodicity underlies all the processes of nature and its study would lead a man out of the world of objective effects into that of subjective causes.”
--Alice A. Bailey (English Writer, Spiritual Teacher and Founder of the Arcane School, 1880-1949)

“At the heart of each of us, whatever our imperfections, there exists a silent pulse of perfect rhythm, a complex of wave forms and resonances, which is absolutely individual and unique, and yet connects us to everything in the universe. The act of getting in touch with this pulse can transform our personal experience and in some way alter the world around us.”
--George Leonard (American Aikidoist and Writer, 1923-)

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.

Negative Ions to Help Treat Mania

Last year I talked about some of the nasty problems that can be caused by the hot dry winds that blow in many parts of the planet.

I have just seen that a paper that I was asked to look at a few months ago has just appeared in print, though according to the journal it came out in February!

The investigators used a negative ionizer to augment the treatment of 20 acutely manic people. It was a standard double-blind crossover study with raters who did not know who had received what treatment.

The negative ions did indeed produce a significant improvement in manic symptoms. We already know that atmospheric ions can have an impact on serotonin levels in some parts of the brain, and that could be the mechanism of action.

It is surprising that there has been so little research into such a simple intervention, though it is important to note that the patients were also receiving medications. But it would be valuable to see if such a simple environmental change could modulate serious mood problems before they get to the level of needing hospitalization.

Brain-Derived Growth Factors and Bipolar Disorder

As we are learning more about the plasticity of the brain, and the way in which new neurons can continue to grow throughout life, there is a great deal of interest in factors that stimulate the growth or development of neurons. This is particularly important in condition like schizophrenia and bipolar in which cognitive decline may occur.

Researchers from Portugal presented some interesting new data (NR68) on Monday at the 2007 Annual Meeting of the American Psychiatric Association in San Diego, California. Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF), one of the most common neurotrophic factors in the brain, may be associated with the pathophysiology of bipolar disorder. The data has been a bit of a mixed bag: previous studies have suggested that BDNF may be associated with either a worse or better neurocognitive outcome in tests of frontal lobe function.

The researchers examined 28 people with bipolar disorder whose mood was currently normal: i.e. they were euthymic,  and they compared them with 25 healthy volunteers. They measured BDNF levels and performed a battery of neuropsychological tests.

The people with bipolar disorder had clear evidence of problems with attention and executive function even when their mood was normal. However it does not seem to have much to do with BDNF: the levels were the same in both patients and healthy volunteers. There was an association between BDNF levels and memory in people with bipolar disorder. This makes sense: BDNF has been implicated in the formation of memory traces in the brain.

What this means is that problems of attention and executive function are likely to be trait-markers of bipolar disorder, while BDNF levels may be a state-related biological marker.

It is interesting how the wheel keeps turning: the person who first differentiated dementia praecox (schizophrenia) from manic depression (bipolar disorder) was Emil Kraepelin. He originally said that people with dementia praecox became worse over time, because of progressive cognitive decline, while people with manic depression did not. When he passed away in 1926 he was working on a whole re-visioning of mental illness, saying that the two could not be so clearly differentiated, because cognitive decline could occur in either illness.

Many pharmaceutical companies are looking into the possibility of improving cognition in major mental illnesses, but there are also a great many non-pharmacological interventions  that can be done to help cognition in people with major mental illness.

Lithium and Brain Growth

There’s an interesting story about the way that lithium was found to be helpful to some people with bipolar disorder. It was thought that there was a link between bipolar disorder and gout, and gout is caused by an accumulation of uric acid in some joints. It just so happens that lithium is very good at getting guinea pigs to pass any excess uric acid in their urine. So in 1949 a medical scientist in Australia called John Cade tried lithium in bipolar disorder. It worked, but not because of any effect on uric acid: the lithium/uric acid connection only works in guinea pigs. But now, all these years later, it turns out that there may actually be a link between bipolar disorder and uric acid after all: uric acid levels often rise in people who are insulin resistant, and insulin resistance is a common feature of bipolar disorder.

The last few years have seen the growth of an impressive body of evidence about the effects of lithium on the brain.  Lithium modulates the way in which many neurotransmitters act in the brain. That raised interesting questions, because many of the chemical transmitters do not only send messages between neurons, they may also stimulate the growth of cell processes and perhaps neurons themselves. Then it was discovered that lithium protects neurons by increasing the levels of a neuroprotective protein called Bcl-2. Then it was found to help stimulate the production of new neurons (neurogenesis) in the hippocampus.

A major breakthrough came in 2000, with the demonstration that lithium increases the amount of gray matter in the human brain, probably by stimulating the production of a growth promoter called brain-derived neurotrophic factor. Gray matter is composed primarily of neurons, so this suggested that lithium was either stimulating the growth of new neurons, or causing the migration of neural stem cells, or alternatively somehow preventing the death of neurons.

Within less than two years it was confirmed that treatment with lithium increased the amount of gray matter in the brains of people with bipolar disorder.

The findings remained controversial for two reasons: first was the seeming impossibility of stimulating the production of new gray matter. That is no longer such a problem: there is more and more evidence that the adult brain can indeed produce new neurons. The second problem was technology: the measurements were open to different interpretations.

Now neuroscientists at UCLA, using brain scans collected by collaborators at the University of Pittsburgh School of Medicine have shown that lithium does indeed increase the amount of gray matter in the brains of patients with bipolar disorder. But what is far more important is that the effects are seen in precise regions of the brain that are thought to be implicated in bipolar disorder.

The research is published in the July issue of the journal Biological Psychiatry.

Carrie Bearden, a clinical neuropsychologist and assistant professor of psychiatry at UCLA, and Paul Thompson, who is associate professor of neurology at the UCLA Laboratory of NeuroImaging, used a novel method of three-dimensional magnetic resonance imaging (MRI) to map the entire surface of the brain in people diagnosed with bipolar disorder. Everyone interested in the brain has been amazed by the quality of the images coming from the UCLA lab over the last six or seven years. (Graphics from the study, including the one above, are available online here.)

When the researchers compared the brains of bipolar patients on lithium with those of people without the disorder and those of bipolar patients not on lithium, they found that the volume of gray matter in the brains of those on lithium was as much as 15 percent higher in the cingulate and paralimbic regions of the brain, that are critical for attention, motivation and emotional control. There was no change in the amount of white matter, telling us that these effects are unlikely to be either artifacts or swelling of the brain.

These are extraordinary findings that may help explain how lithium works. If lithium increases the amount of gray matter in specific regions of the brain, this may suggest that existing gray matter in these regions may be underused or dysfunctional in people with bipolar disorder.

Conventional MRI studies in bipolar disorder measured the total volume of the brain, but these new imaging techniques employ high-resolution MRI and cortical pattern-matching methods to map gray matter differences that are so precise that they can pick up subtle differences in brain structure and this is the first time that researchers have been able to look at specific regions of the brain in people with bipolar disorder, and examine the effects of treatment.

The researchers at UCLA analyzed MRI scans of 28 adults with bipolar disorder, 20 of whom were lithium-treated, and 28 healthy control subjects collected by collaborators at the University of Pittsburgh. The analysis involved detailed spatial analyses of the distribution of gray matter by measuring local volumes of gray matter at thousands of locations in the brain.

This is superb research, and one of the signs of good research is that it raises yet more questions:

• We do not know whether these effects on gray matter persist once the medicine is stopped.
• Neither do we know whether the same effect might occur in other illnesses in which there is loss of gray matter. It may just be that lithium corrects an abnormality that is specific to bipolar disorder. That being said, there is recent evidence that lithium may be neuroprotective in a mouse model of Alzheimer’s disease.
• We also do not know if these brain changes correlate with clinical improvement.
• Lithium can have a lot of side effects, so we shall also need to factor that into the equation.
• We also need to know whether other medicines - or any other kind of therapy - might produce similar effects: there are already several medicines that have been shown to do something similar in some animals.

It's still a bit too early to suggest putting lithium in the water supply...

Schizophrenia, Psychosis and Psychopathy

Ever since the tragedy in Virginia earlier this week, everyone has been trying to second guess what happened. As I said, to the trained eye there is a lot to suggest that he had a psychotic condition, but whether it was schizophrenia, bipolar disorder or psychotic depression is guess work.

One of the things that has been worrying in all the media coverage has not only been the sensationalism that we have seen in some quarters, but the mistakes that reporters - and even some of the "experts" - have made in talking about mental illness. I have heard people constantly mixing up schizophrenia and psychopathy, which is more accurately called antisocial personality disorder. I have even heard an old mistake that I had thought died years ago: that schizophrenia is a "split personality." I think that mistake probably goes back to a misunderstanding of the roots of the term "schizophrenia," and it was perpetuated by Alfred Hitchcock's movie Psycho in 1960.

Let me just repeat: schizophrenia is NOT a split personality. Neither is it multiple personality disorder. There is even a lot of discussion whether multiple personality disorder, now known as "Dissociative identity disorder" really exists: a discussion for another day.

Because there has been so much confusion, I thought that it would be good to clarify what each of these disorders is.

You can get some of the information from Wikipedia. What has worried me a bit is that some websites have slightly questionable infrmation. Many people know that I do a great deal of advocacy work for the mentally ill, so these notes are from my own lectures.

For reliable back up information, I recommend using Healia.com to search, and you can check out at Wikipedia, Schizophrenia.com, the National Institute of Mental Health website, Medline Plus and the National Alliance for the  Mentally Ill.


Psychosis
Psychosis is simply a generic term for a mental illness in which people have a "loss of contact with reality." There are often other symptoms, such as hallucinations, delusional beliefs, disorganized thinking and a lack of insight into the unusual or bizarre nature of his or her behavior. Almost anything that stresses the nervous system enough may lead to psychosis. I have often told students that it is possible to induce psychosis in just about anyone. It is a symptom and not a disease. We sometimes call it the "fever of the nervous system."


Schizophrenia
This is a group of illnesses that describe a mental disorder characterized by impairments in people's perception or expression of reality and by significant social or occupational dysfunction. The point is that other people don't share their view of reality and it is causing suffering. There is always some smart Alec student who says, "But isn't religion a delusion?" The answer is no, of course it isn't. Millions of people share the same beliefs. The second piece is also important: is it causing suffering, distress or disability? Many people have ideas that are "different." That does not mean that they are mentally ill. Professionals should not get involved unless the beliefs are causing a problem.

A person experiencing schizophrenia typically has disorganized thinking, and may experience delusions or hallucinations. In Western cultures these are most commonly auditory hallucinations. Simply having hallucinations does NOT mean that someone is mentally ill. I seem to be one of the few psychiatrists that supports the aims of the Hearing Voices Network. The Network tries to help people who are experiencing hallucinations and to educate the public and professionals that there are many possible reasons for hearing voices and many have nothing to do with mental illness.

One of the most disabling things about the schizophrenic group of illnesses is that they primarily affect  cognition, and that is one of the things that can lead to chronic problems with behavior and emotion. For a long time there was a worry that the cognitive problems were a result of being on some of the older medications. But these cognitive problems were identified decades before the introduction of these medicines. Hence the old name of schizophreia: dementia praecox.

The diagnosis is based on self-report and observation. We do not have a laboratory test for these illnesses, but we are finding reproducible changes in the brain and in many genes. The main evidence for the illnesses is still based on their response to treatment.

There has been a lot of discussion about whether we should abandon the term "schizophrenias," since the current diagnostic approach is flawed: many people have psychotic experiences without becoming dsitressed or disabled. Neither can they - or should they - be diagnosed. This gets back to the categorical and dimensional argument that I have talked about before. The second point is that the label "schizophrenia" can be so stigmatizing.


Antisocial Personality Disorder
Antisocial personaity disorder is also referred to as psychopathy, sociopathy or dyssocial personality disorder. It is a condition characterized by lack of empathy or conscience, and poor impulse control or manipulative behaviors. The term originally came from the Greek psyche (meaning soul, breath or mind) and pathos (to suffer). At one time the term was used to describe all mental illness, and that is why there is confusion. It is quite different from psychosis. Psychosis is a chronic or intermittent symptom that comes on at some time in life. Antisocial personality disorder should have been present all the time, even though we cannot formally diagnose it until the age of eighteen. The term "psychopath" is not a good one: it has no precise equivalent in either the DSM-IV-TR or the ICD-10.

Only a minority of diagnosable psychopaths are violent offenders . There has been a lot of discussion about whether the manipulative skills of some of the non-violent psychopaths are valuable in corporate America, the military and academia, because they may bold and often charismatic leaders. The has even been a suggestion that becoming a "psychopath" may be an adaptation to working in a highly competitive environment: it gets results for both the individual and for their corporations or countries.

There is a recent book - Snakes in Suits - that does a good job of exploring these ideas.

In summary:
Psychosis = A symptom
Schizophrenia = A group of acute or chronic illnesses in which psychosis is a central feature
Antisocial Personality Disorder = a.k.a. "Psychopathy:" life long personality trait

   

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!

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.”

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.

Psychiatry Below the Neck

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

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

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

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

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

A New Understanding of Mood Medicines and Cells

We are in the midst of a revolution in our understanding of how many medicines work. Most students are still taught that the key to their actions is simply a matter of binding to a receptor, and then some magic occurs in the cell. But over the last few years there has been a sea change in how we see the actions of many medicines. In many ways the focus on receptor pharmacology is so 1990s.

Several years ago our group and others began to speculate that one of the ways of modulating the interaction of insulin with cells was to modify the characteristics of the cell membrane in which the insulin receptors sit. If we could change the fluidity of the cell membrane, then we could change the sensitivity of the insulin receptor. We also went a bit further and wondered whether high cholesterol levels might be associated with coronary artery disease because it changed the way in which growth factors interacted with cells in the vessel walls.

One of the reasons that fish oils may yet turn out to be helpful in some mood disorders is because they may change the behavior of cell membranes and therefore the behavior of receptors.

I have admired the work that has bee done by Husseini Manji and his group that is now at the National Institute of Mental Health in Bethesda, Maryland. Their interest is in bipolar disorder and there is a very nice update on the group’s work in the journal Biological Psychiatry.

The group is unraveling the ways in which effective medicines work at the cellular level and what actually goes wrong in bipolar disorder. We know that people with severe mood disorders may experience regional impairments of what we call structural plasticity and cellular resilience. This means that the cells find it more difficult to learn and respond to environmental changes. We think that this is why some people with severe mood problems fail to benefit from many medicines and also have so many long-term cognitive problems. So the search is on for strategies that may enhance and maintain the normal connections between neurons. The good news is that there are several new strategies on the horizon.

This notion of impairment in the normal plasticity and resilience of the brain is also why psychosocial approaches are an essential component of successful treatment. When they are coupled to the right medicine as well as the strategies that we employ in Integrated Medicine, the effects can often be very gratifying.

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.

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.

The Epigenetic Code

In Healing, Meaning and Purpose I reveal some of the extraordinary changes that are occurring in our understanding of genetics and inheritance. Even if you are currently learning genetics in college, it is quite likely that some of what your professors are teaching may already be out of date. I say that with the greatest possible respect: I find that in some of my fields of expertise, I am often having to update my teaching materials every week.

One of the remarkable discoveries that is generating huge amounts of new information is what we call epigenetics. This is the study of a form of inheritance that can occur without fundamental changes in gene sequences. This has to do with the idea that there is a second layer of programming on top of our DNA. A code that can change over our lifetimes in response to environmental change. Diet, hormones, chemicals in the environment, stress and even thought, emotion and behavior, can all change the ways in which our genes are expressed. Some of these epigenetic changes can be passed on to other generations. In other words, there can be an inheritance of acquired characteristics. Something that has been denied for over a century.

Let me give you a simple example. Studies of a particular species of mouse have shown that maternal diet has an effect on the coat color of the offspring. This was the result of what is known as methylation that altered gene expression. These changes in coat color were carried on to the next generation: the grandchildren of the mouse given the special diet. This created quite a stir, because it had been thought that epigenetic changes in cells are erased each time that a cell divides. Obviously that was not happening. We now have many examples of epigenetic changes being passed on to the next generation and the next. There are literally hundreds of scientific papers on the subject.

As I have written before in my last book and CDs, in articles and in reviews at Amazon and elsewhere, the traditional view of genetics has been one of genetic determinism. That we are all little robots whose entire lives are dedicated to nothing more than passing our DNA from one generation to the next. And the genes even dictated how we did that. I still know many gene jockeys who are convinced that the whole of human behavior will ultimately be explained by our genes, and that free will is therefore a myth.

I’m just as sure that they are wrong.

Let me give you an example. Identical twins have identical DNA, yet we have known for fifty years that one twin may get a genetic illness that the other does not. And the brains of identical twins, though they start out identical, quickly become quite different from each other because of the impact of the environment. Twin studies of mental illness have been going on at the Institute of Psychiatry in London since 1960. Every patient coming to the hospital is asked by the clerical staff if he or she is a twin. And there has been groundbreaking research on mentally ill twins at the National Institute of Mental Health for decades. And what have we learned? Though there may be a genetic component in schizophrenia, when we look at people with schizophrenia who have identical twins, only half of the twins have the illness, despite having the same DNA. The key difference is at the epigenetic level.

Marcus Pembrey from the Clinical and Molecular Genetics Unit at the Institute of Child Health, part of University College, London, has been at the forefront of the work on epigenetics. Marcus has had the opportunity to study the unusually detailed historical medical records of the isolated northern Swedish city of Overkalix. He and his colleagues found something astonishing. The grandsons of men who experienced famine during mid-childhood went through puberty earlier and had longer life spans, while the grandsons of men who were well fed in early childhood had an increased likelihood of diabetes. For females, the effect was similar but it was tied to the grandmother, rather than the grandfather. Presumably these responses are designed to adjust our early growth and reproduction to be ready for unpredictable changes adverse events in the environment. I would call this epigenetic resilience.

In a separate study done in Bristol in England, Marcus studied two generations of families, and found that fathers who had started smoking before age 11 had sons who were significantly heavier than average. There was no similar effect on daughters.

There is already some evidence that epigenetic factors may play a role in the development of bipolar disorder and schizophrenia.  Many of us are becoming excited about the potential benefit that may flow from a better understanding of genetic and epigenetic mechanisms in major psychiatric disorders.

There is a new journal called, appropriately, Epigenetics that contains a treasure trove of important information. The editor is Moshe Szyf, form McGill University in Canada, and he recently pointed out that one single gene could have as many as 700 epigenetic programs associated with it.

His own research has linked epigenetic change to social interactions: the way in which we behave toward one another can lead to a change in how our genes operate.

Rats whose mothers groom and lick them when they are young grow up to be much calmer than rats whose mothers neglected them. There is, of course, nothing surprising about that. We all understand the importance of good child rearing. But what was surprising was the finding that epigenetic changes are the cause. By nurturing their young, the rat mothers activated a gene that suppressed the creation of cortisol, one of the stress hormones.

Pups who were neglected did not have that gene activated, so they produced more cortisol and were therefore more stressed out.

Knowing this, the researchers were able to increase the well-nurtured rats' stress by injecting them with methionine, an amino acid commonly found in food supplements.

Here we have proof that the link between food and mood is not just due to transient chemical changes in the neurotransmitters of the brain, but that a chemical in our diet could cause fundamental changes in the way in which our genes work. In this case a rat’s emotions and state of mind. The implications for all of us are extraordinary.

Since 2003, a consortium of public and private firms in Europe has been working on the first Human Epigenome Project (HEP), and it hopes to have completed 10% of the map by the end of this year. As you can see, it is a lot more complicated than mapping the human genome, and epigenetic codes are constantly moving targets. The first reports from HEP have indicated that at least 20% of the genes studied so far can have their behavior modified by the environment. The food that we eat, the chemicals that we ingest and the attitude of our parents and peers can all change the way in which our genes function. As Marcus Pembrey has said, “Child care has a whole new meaning.”

This is all crucially important, because one of our most important discoveries has been that human beings have been undergoing extremely rapid physical as well as psychological and social change, and that is one of the reasons why the Laws of Healing have been changing over the last century.

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.

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!

Gall Bladder Disease and Insulin Resistance

When I was a young student, everyone learned that gallstones were more common in people who were “Fat, female, fair and forty.” As you can see we lived in different times and nobody would say anything quite like that today. Not least because it’s now only partially correct. Gallstones are occurring at ever-earlier ages, because they are a recognized complication of obesity. And we all know that we are in the midst of a pandemic of overweight and obesity.

We have also been remarking on the number of people with bipolar disorder who have a history of gallstones.

For many years now, the explanation for the link has been to do with an increasing levels of cholesterol, which are a major precipitant of gallstones. There’s also evidence that high carbohydrate diets increase the risk of gallstones. Weight loss reduced the risk of developing them, though suddenly losing a lot of weight with an unbalanced diet may increase the risk of gallstones.

Now a paper from colleagues at three medical schools has just been published this month, and it helps clarify the connection. The conclusion of the scientists is important: insulin resistance itself seems to cause problems with the normal emptying of the gallbladder, and that would predispose people to the development of gallstones.

Insulin resistance is a feature of increasing weight. Several studies that have found increased rates of insulin resistance in people with bipolar disorder implying an increased risk of gallstones. Though gallbladder disease didn’t show up in a recent study from some friends in Toronto, I could not find any systematic studies of gallstones and bipolar disorder. And it is a study that needs to be done.

So there’s a tip for a researcher who can’t think of a project!

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.

Infomania

Here’s a study that came I under the radar, but is an important contribution to our on-going discussions about the perils of multi-tasking.

Glenn Wilson, a psychologist at my alma mater in London did a most interesting study funded by, of all people, Hewlett Packard.

It was a postal study carried out at the Institute of Psychiatry in London, and the main finding was that excessive use of technology reduced workers' intelligence.

Those distracted by incoming email and phone calls were fond to have a 10-point fall in their IQ. That would be more than twice that found in studies of the impact of smoking marijuana. People who are constantly breaking away from tasks to react to email or text messages suffer similar effects on the mind and the brain as losing a night's sleep

More than half of the 1,100 respondents said they always responded to an email "immediately" or as soon as possible, with 21% admitting they would interrupt a meeting to do so.

Do we really need any more evidence to confirm the dangers of multitasking and constant partial attention?

I don’t think so.

Therefore I’m going to continue to publish tips and techniques for dealing with the barrage of information that threatens to drown us.

Even before the oceans begin to rise….

Bipolar Disorder, Insomnia and Suicide

For many years now, I have advised on the treatment of many well-known people with all sorts of problems and illnesses. I always admire people who reveal that they have suffered from a problem in the hope of helping other sufferers.

The actor Stephen Fry has recently described his struggles with bipolar disorder and why he suddenly abandoned a play in London after developing stage fright. You may have seen him playing Jeeves to Hugh Laurie’s Wooster, or in the Blackadder shows.

Stephen was once described as a man with a “Brain the size of Kent.” He said that he became so knowledgeable because of terrible insomnia, which kept him up nights: he used the time to read enormous numbers of books. He also described a suicide attempt and a very serious plan to kill himself.

Though I've not examined Stephen, I can now explain several things to you:
1.    Bipolar disorder is not uncommon, and is rather more common in highly creative people. That being said, we must not romanticize an illness that carries a substantial mortality. The illness is frequently misdiagnosed, and when it is, there is an ever-present risk of suicide, as well as a host of other medical problems.
2.    Anxiety disorders occur in 80-90% of people struggling with bipolar disorder, and stage fright is one of these anxiety states
3.    Stephen may not have had insomnia as much as a reduced need for sleep, which is a classic symptom of one type of bipolar disorder. People with insomnia cannot sleep and usually go through the day feeling un-rested. People with a reduced need for sleep not only stay awake, but don’t get tired until they have been up for days at a time. Doing something like reading lots of books at night is another classic symptom.

Stephen Fry has just made a documentary for the BBC in which he talks about bipolar disorder with Carrie Fisher, Richard Dreyfuss and Robbie Williams.

They all deserve our gratitude for speaking out, telling their stories, and hopefully helping alleviate some of the stigma of mental illness, and helping more people get the diagnosis and treatment that they need.

Thank you Stephen!

P.S. There has recently been a rumor going round that your humble reporter was the model for Hugh Laurie's Golden Globe award-winning portrayal of Dr. Gregory House. I don't know where it started, but there's absolutely no truth in this vile calumny. I'm never irritable or curmudgeonly...

Technorati tags: Stephen Fry Bipolar disorder Stigma Hugh Laurie Blackadder Gregory House

Migraine and Bipolar Disorder

Back when the world was new, I cut my teeth in migraine research, and migraine and other headaches were the topic of my first book. So I’ve always kept an eye out for new developments.

There’s an interesting case report from India, about a nineteen year old who developed mild mania as part of the aura or warning of his attacks. This sort of case is interesting for what it might be able to teach us about each illness. It is also good for us to know that bipolar disorder is highly co-morbid: it is associated with many other illnesses apart from migraine:
1.    Anxiety disorders
2.    Substance abuse disorders
3.    Attention deficit disorders
4.    Personality disorders
5.    Impulse control disorders
6.    Eating disorders
7.    Insulin resistance
8.    Obesity
9.    Diabetes mellitus
10.  Cardiovascular diseases
11.  Pain disorders

This is why diligent clinicians are always on the lookout for bipolar disorder: if it is missed and remains untreated, it can cause havoc: suicide attempts, damaged relationships, substance abuse and general misery.

Migraine is one of the vascular headaches that is occasionally associated with an array of other vascular problems, like Raynaud’s phenomenon, ischemic heart disease and stroke. But the aura is something else altogether. For many years it was thought that the migrainous aura was a result of a reduction in blood flow to regions of the cerebral cortex. Almost 25 years ago that was shown to be inaccurate. It is due to a release of witches’ brew of excitatory and inhibitory amino acids in the cortex. It is highly likely that the release of excitatory amino acids is the explanation for the manic symptoms.

Migrainous mania is evidently rare, but apart from visual disturbances, I’ve seen all sorts of strange auras: sudden food cravings; intense sweating; extreme irritability and many other things besides.

The treatment of migraine still revolves around avoidance or modulation of triggers, pain relief and prophylaxis. The big change in recent years has been the increasing amount of experience and small amount of evidence indicating the value of non-pharmacological approaches like spinal manipulation, temporomandibular joint adjustment, acupuncture, the tapping therapies and homeopathy.

To an integrated practitioner, the key is to understand the problem as more than just headache: we can guide a person to see the problem in its broader context, as a challenge designed to find a path toward inner wellness. We also see it as a process that has meaning and purpose and is a Divinely inspired invitation to grow spiritually and as an individual.

That may sound a lot for a headache, but it is the best possible way to triumph over the problem!

“The cure of the part should not be attempted without treatment of the whole.”
--Plato (Athenian Philosopher, 428-348 B.C.E.)

Technorati tags: Migraine Bipolar disorder Insulin resistance Attention deficit disorder AnxietyIntegrated medicine

Systemic Psychiatry

“Once a disease has entered the body, all parts which are healthy must fight it: not one alone, but all. Because a disease might mean their common death. Nature knows this; and Nature attacks the disease with whatever help she can muster.”
--Paracelsus (a.k.a. Theophrastus Phillippus Aureolus Bombastus von Hohenheim, Swiss Physician and Alchemist, 1493-1541)

It is usually a mistake to try and look at an illness in isolation.

We are all human beings, and physical challenges affect the whole organism, as well as our mind, our relationships and our spiritual connections.

There is currently a very hot area of research that is still unknown to most people: even to most people working in psychology and psychiatry. This hot new area proposes that schizophrenia, bipolar disorder, major depressive disorder and autistic spectrum disorders, are disturbances affecting the whole body, but with prominent effects in the brain and on emotion and behavior. This may help provide one part of the explanation for why people struggling with chronic mental illness - and their relatives - suffer from an array of physical illnesses that cannot be explained by stress or poor lifestyle choices alone.

You can find a brief review with a stack of references here.

This idea of psychiatric problems being generalized systemic disturbances that have their primary effects on the brain and on behavior is important to the general themes of this blog. We are always interested in looking beyond the obvious causes, to a dynamic integrated vision of a person that includes every part and every dimension of his or her being. If we want to help people recover from illness, to triumph over adversity, and to use challenges as springboards to transcend themselves and the limits placed upon them, it is only possible if we take account of the whole person.

Perhaps we can reduce mental illnesses to disturbances in cell membranes or a few chemicals in the brain. But I do not think so. It is more accurate for us to be thinking about a perturbation or disturbance in the Informational Matrix that underlies the subtle systems of the body, that in turn support the biochemical reactions that provide the structure for the external expression of life itself.

We live in very interesting times.

“Good timber does not grow with ease. The stronger the wind the stronger the trees.”
--Willard J. Marriott (American Businessman and Founder of Marriott Hotels, 1900-1985)

Technorati tags: Schizophrenia Bipolar disorder Diabetes mellitus Phospholipid Cell membrane Systemic illness Informational matrix 

Helping to Prevent Suicide

Unless you work in psychology or psychiatry, you may not know that in the United States, there are considerably more suicides each year than there are murders.

Though there is sometimes little warning that someone might be about to harm themselves, in the majority there have been some warning signs.

The American Association of Suicidology expert consensus panel has just published a mnemonic to help professionals and the general public recognize some of the major risk factors. You can find a brief article with a link here.

Here is the whole mnemonic:
I    Ideation
S    Substance abuse

P    Purposelessness
A    Anxiety
T    Trapped
H    Hopelessness

W    Withdrawal
A    Anger
R    Recklessness
M    Mood changes

This is only a first attempt at an evidence-based summary of some of the major risk factors, and the sensitivty and specificity of the list is still quite low. But If awareness of some of these warning signs and risk factors saves even a single life, this post will have been worthwhile.

Technorati tags: Suicide Depression Self-harm

Diagnosing Illnesses

I am pleased to say that my recent item about Categorical and Dimensional ways of looking at illnesses has provoked some spirited correspondence and questions. Far from indicating that the art of diagnosis is arbitrary and vague, it reflects clinical reality. I get a great many magazines and articles from supporters of alternative medicine, and some have so misunderstood the principles of diagnosis that they think that illnesses don't exist! One of the reasons for this flawed thinking is that we all have a bad case of physics envy. The success of Newtonian physics and Humean philosophy has seduced us into thinking that everything has a single cause, and that every item and every event has clearly defined boundaries.

We are complex and ever-evolving individuals and we are also members of of constantly changing groups, so we have to be seen not only as "objects" wth diagnostic labels, but also as people with a time and developmental dimension: you and your life challenges will change over time as you continue to develop and evolve. As the great Scottish poet Robert Burns said: “Nature's mighty law is change.”

I think that is important to let you know how this field is developing, and why it is that we cannot always come up with a cut and dried answer to the question "Well, what has he got then?"

On May 24th, I wrote a short article about the inter-relationships between schizophrenia and bipolar disorder that you may find interesting. It develops some of the points that I made in my previous article.

Technorati tags: Diagnosis Category Bipolar disorder Schizophrenia

Creativity and Promiscuity

What do Lord Byron, Dylan Thomas and Pablo Picasso have in common? Not only were they all creative, they also had lively and probably exhausting sex lives. British researchers have recently found evidence that this connection may be no coincidence.

Daniel Nettle from the University of Newcastle upon Tyne and Helen Clegg of the Open University have spent some years examining the puzzle of schizophrenia. This is without doubt one of the most savage and distressing illness to afflict humanity. There is a heritable component, yet sufferers themselves often find it very hard to maintain relationships, have many physical illnesses and tend to have fewer children themselves. Yet the illness persists, and indeed appears to have become far more common in the middle of the 18th century, roughly coinciding with the beginning of the Industrial Revolution. The question then is whether some mild forms of the illness may have survival advantage. Theses investigators have been looking at some of the personality traits that may be predictive of schizophrenia. They found high rates of what is known as “Schizotypy” amongst the artists and poets.

The typical features of schizotypal personality disorder are:

1. Unusual experiences, including odd perceptions, magical thinking and sometimes hallucinations

2. Cognitive disorganization

3. Impulsivity

4. Non-conformity with regard to rules and social conventions

5. Often introverted, though some become overly sociable

People with schizotypal personality may develop schizophrenia symptoms if stressed, and they are found more commonly in the families of people with full-blown schizophrenia.

Psychologists have previously found that the creativity of professional artists and poets acts almost like a sexual magnetic, and it has long been thought that creative people are more likely to engage in increased sexual activity, but this research is the first to prove it. The average number of sexual partners for artists and poets was between four and ten, compared with three for non-creative types. Statistics also showed that the average number of sexual partners for both men and women rose in line with an increase in the amount of creative activity.

Links have been made before between bipolar disorder and creativity and also between creativity and schizotypy. An essential feature of creativity is the ability to put together unusual associations and ideas. In the schizotypal person who is creative, this is kept in balance, but in schizophrenia these association can become bizarre. Schizotypy tends to be associated with cognitive activation and sometimes greater sociability.

Apart from art and poetry, it is an open secret in the psychiatric community that several Nobel Prize-winning scientists have schizotypy, at least two have been diagnosed with schizophrenia, including John Nash of Beautiful Mind fame, and several famous Nobel Laureates have first-degree relatives with schizophrenia. The numbers are much higher than in the general population.

Some commentators have suggested that if you want to be lucky in love, perhaps you need to be more creative. We cannot all be a Byron or a Picasso, but I would suggest that injecting a little more creativity into your current relationships and if you are looking for new ones, being more open and creative about how and whom you meet, will likely make encounters more congenial for both of you.

Technorati tags: creativity, schizotypy, Picasso,