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.

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