Today we go back to the basics of depression. Borodin's Nocturne (right click to open in new tab).
I would say there are three main theories held by the general public about the causes of depression:
1) Bootstrap theory: you are a lazy good-for-nothing who just needs to snap out of it and get up and get yourself better.
2) Trauma theory: too much stress, death, trauma, etc.
3) The chemical imbalance: You have an SSRI deficiency and your serotonin needs to be regulated (see this memorable old zoloft commercial)
Of course, I don't subscribe to any of these theories entirely, though there are elements to each of them that hold a kernel of truth - my belief and one that is largely supported by the literature is that stress and genetic susceptibility leads to depressive symptoms, which are mediated by inflammatory means in the brain. And certainly if one is capable, getting up and getting out and exercising and eating right can be very helpful, but sometimes asking a depressed person to wake up early and exercise is like asking someone with a broken ankle to go for a run. The frontal lobe isn't firing on all cylinders. There's no motivation, no zazz.
The scientifically minded probably are most familiar with theory number three. In medical terms, the "chemical imbalance" theory is called the "monoamine hypothesis" of depression. The monoamine theory is (I would say) largely accepted by doctors of a certain age (even psychiatrists), but it holds about as much water as the carbohydrate-insulin theory of obesity. Back in the day there was a medication for blood pressure called reserpine. Among other things it depletes the brain of serotonin, and does indeed tend to cause depression (it is rarely used nowadays).
The first antidepressant, a drug used to treat tuberculosis, was found serendipitously. One of its actions was to change the concentrations of monoamines (such as serotonin and norepinephrine) in the synapse between nerves. And thus, the monoamine hypothesis of depression was born along with a billion dollar antidepressant industry. All the antidepressants affect the monoamines one way or another, and they work… if you are lucky, often with side effects, and maybe they protect your brain during one episode of depression, but they don't seem to protect you from the next episode if you go off the medicine when you feel better (talk therapy when compared to medicines seems to have more long term benefit, not surprisingly).
Along the way, the monoamine theory picked up a bunch of other diseases (called the affective spectrum disorders) including major depressive disorder's anxious twin, generalized anxiety disorder, migraines, irritable bowel syndrome, bipolar disorders, social phobia, PTSD, OCD fibromyalgia, and chronic fatigue syndrome among others (1). All of these diseases have been shown to respond (somewhat) to three or more different classes of antidepressant medication.
Problem is, when you measure serotonin in depressed people, the levels are often all over the map. In fact, low serotonin doesn't really correlate with depression very well at all, though low serotonin in the central nervous system does correlate with suicide, violence, and insomnia. Brain researchers quickly figured out that the monoamine hypothesis has some pretty big holes, and the mechanism of antidepressants is not about increasing serotonin and other monoamines in the synapse but rather changing the efficiency with which monoamine signals are transmitted.
Instead, the current literature-supported theory of the brain pathology of depression and the other affective spectrum disorders leads us to two things going awry - the immune system (inflammation) and mitochondrial dysfunction.
How messy is the study of depression? Consider these facts - if we look at the modern criteria, the classic unipolar major depression is a smallish subset of the whole. 31-62% of people with depression have symptoms of "atypical depression" (leaden feelings in the arms and legs, increased appetite, increased sleep, as opposed to the classic weight loss and insomnia). 64-72% of those with atypical depression meet criteria for bipolar spectrum disorders. Depressive disorders are often comorbid with ADHD, anxiety, and substance abuse disorders. You can see if we try to study a group of patients with "major depressive disorder" by criteria that represents the typical clinical outpatient, we will get a mix of people with various complicating neuropsych problems, and any studies of so-called "pure" major depressive disorders where other problems are excluded (which is typical for pharmaceutical studies) will not necessarily be generalizable to the actual population.
Add in frequent comorbid medical conditions, and you have a whole soup of pathology. 92% of depressed inpatients have pain, typically headaches or muscle aches. Irritable bowel and migraines are often found, along with metabolic syndrome, pre-diabetes and diabetes, and obesity.
However, rather than be taken aback by the complexities, theories of mitochondrial dysfunction and inflammation can scoop up the entire variable pathology (which makes these theories very pleasing to me).
So let's start with mitochondria. As we know, these are the energy factories of the cells, and their primary mission is to make the cellular equivalent of gasoline, ATP. Problems with the mitochondria tend to show up as symptoms with the most energetically hungry cells of the muscle and nerves. Nutritionally, CoQ10, carnitine, B-vitamin, and selenium deficiencies can also cause mitochondrial dysfunction directly. Mitochondria desperately need these micronutrients to do their work efficiently.
Symptoms of mitochondrial dysfunction can be non-specific, but the cognitive symptoms are very similar to those found in depression, including impairments in attention and executive function and memory. Tellingly, in families with known genetic problems with mitochondria, the symptoms worsen around times of stress - overwork, fasting, over-exercise, and environmental temperature extremes. Children with mitochondrial disorders are more likely to be depressed than control children, and among adults, folks with known mitochondrial disorders are more likely to have depression, chronic fatigue, major depressive disorders, bipolar disorder, and panic disorder than the general population.
But all of that is the typical chicken and egg clinical stuff. Maybe people with genetic mitochondrial problems have a lot of stress, and are thus more depressed. What's the biochemical evidence for mitochondrial dysfunction in major depressive disorders (and bipolar disorder)? Autopsies show all sorts of interesting problems with mitochondrial proteins, unusual mitochondrial DNA mutations, and poor mitochondrial complex activity (2). ATP production rates and respiratory chain enzyme ratios seem to be decreased in the muscle of biopsied patients with major depressive disorder and pain. In fact, several studies have shown that patients with a high degree of somatic complaints (typically muscle aches) have much lower ATP production than average in the muscle. In chronic fatigue patients, some similar abnormalities have been found.
And finally, in some mouse models of mitochondrial dysfunction, the mice have bipolar-like symptoms and altered levels and turnover of the monoamines. The researchers worked out that the mitochondrial dysfunction was the cause of the monoamine depletion, leading to the mouse mood disorders.
So mitochondrial problems (which can be brought about genetically, but also by micronutrient deficiencies) can cause oxidative stress, and eventually lead to nerve damage and psychiatric symptoms. More on the specifics of this pathology and the role of inflammation in the next post.
Monday, November 28, 2011
Thursday, November 24, 2011
Tales of the Metabolically Deranged
Happy Thanksgiving! I'm probably in too good of a mood to write this post properly, but I have a moment right now and must seize the opportunity, and I'm going to try to make this short but cogent. A few days ago I noted that I don't agree with Mercola and Rosedale about their characterization (paraphrased, as it wasn't quite as black and white) of glucose as toxic and human beings as on a linear path to diabetes. Whether or not anyone cares about my opinion as a psychiatrist is another question :-) Commenter js290 wrote the following:
I wrote that I read the articles a couple of times, and found them flabbergasting. Js290 wrote back:
I disagree with the characterization that the "derangements" are linear. My understanding of physiology is that those with healthy beta cell function can do very well with a wide variety of carbohydrate intake and it shouldn't matter that much for optimal health. We are obligated to use glucose for fuel - we have systems in place to deal with physiologic amounts of glucose. I also don't think that post-prandial glucose "spikes" are particularly abnormal or dangerous unless they are very high and last a long time. I don't think glucose or carbohydrates as a macronutrient class per se cause diabetes. Once you get past a tipping point and start taking out beta cells, hyperglycemia, insulin resistance, and increasing damage occurs, then you have fewer options, dietarily speaking. Even then, a hard core ketotic zero carber who never cheats may be in good stead, but those who cheat are now (physiologically) even more insulin resistant than they would have been if they ate enough carbs to keep them out of deep ketosis all the time… so glucose "spikes" and area under the curve for glucose and insulin would be even higher than if there were more carbs eaten on a regular basis.
In addition, since the liver will make a bunch of glucose via gluconeogenesis, I don't see much harm in eating moderate amounts of glucose so our liver doesn't need to make it, unless you are needing to stay in deep ketosis for medical reasons. Six of one, half a dozen the other.
And, of course, I think there are certain brain illnesses that could very well benefit from deep ketosis (for some of these conditions it is merely theoretical, for others there are case studies or even pilot data, for epilepsy there is a lot of data) - brain cancers, migraines, epilepsy, bipolar disorder, dementia, autism, and schizophrenia.
In general, I think it is reasonable that fasting and autophagy should be engaged in on an intermittent basis for all individuals, including heathy ones - I know that if on one particular day I personally eat high carb or low carb, I wake up the next morning in ketosis. That is a sign of metabolic flexibility, which is a positive sign of a healthy metabolism.
Well, that is my opinion. Starchy root vegetables and fruit are good sources of nutrients and in general less expensive than good quality meat, though perhaps not less expensive or easier to store than than good quality fat, calorie for calorie. The nutrients in starch tend to be somewhat different than the ones in fat. I find them pleasurable to eat, personally, and my kids certainly prefer the starch and fruit to just fat, green leafy vegetables, and meat. Perhaps they would truly want mountains of candy and chocolate and their preferences shouldn't guide our health speculations… well, that's my opinion. I simply don't think there is enough evidence to suggest that zero carb diets are optimal for everyone for longevity and health, either from an experimental perspective or from a common sense, physiologic perspective.
You should read more carefully what Dr. Rosedale wrote in the link you supplied. Your characterization of it is entirely [sic] accurate.
I wrote that I read the articles a couple of times, and found them flabbergasting. Js290 wrote back:
The way I read it, Dr. Rosedale offered the most generalized solution. The abstraction he makes is we simply define a gradient of metabolic derangement from 0% (healthy) to 100% deranged (diabetic). His argument seems to be simply, the diet that is therapeutic for fully metabolically deranged cannot be unhealthy for the metabolically healthy.
Analogously, it's similar to most of the paleo stance on gluten grains: just because it's tolerable doesn't make it optimal.
Given that you have written about brains function on ketones, that for the same number of carbon atoms, fatty acids produce more ATP than glucose, that the body is capable of producing all the glucose it needs, Dr. Rosedale's view is by far the most generalized and better abstraction from a health perspective.
Why come up with many different models for different use cases when a single model will work? This is how evolution and natural selection does things: the best abstraction wins.I think js290 encompasses in a nutshell exactly why I find the theories so puzzling. I don't see why we should use sick people to tell us what is optimal for all people. Nor do I know the definition of "metabolically deranged" - do we mean pre-diabetic and type II diabetic? Obese? Metabolic syndrome?
I disagree with the characterization that the "derangements" are linear. My understanding of physiology is that those with healthy beta cell function can do very well with a wide variety of carbohydrate intake and it shouldn't matter that much for optimal health. We are obligated to use glucose for fuel - we have systems in place to deal with physiologic amounts of glucose. I also don't think that post-prandial glucose "spikes" are particularly abnormal or dangerous unless they are very high and last a long time. I don't think glucose or carbohydrates as a macronutrient class per se cause diabetes. Once you get past a tipping point and start taking out beta cells, hyperglycemia, insulin resistance, and increasing damage occurs, then you have fewer options, dietarily speaking. Even then, a hard core ketotic zero carber who never cheats may be in good stead, but those who cheat are now (physiologically) even more insulin resistant than they would have been if they ate enough carbs to keep them out of deep ketosis all the time… so glucose "spikes" and area under the curve for glucose and insulin would be even higher than if there were more carbs eaten on a regular basis.
In addition, since the liver will make a bunch of glucose via gluconeogenesis, I don't see much harm in eating moderate amounts of glucose so our liver doesn't need to make it, unless you are needing to stay in deep ketosis for medical reasons. Six of one, half a dozen the other.
And, of course, I think there are certain brain illnesses that could very well benefit from deep ketosis (for some of these conditions it is merely theoretical, for others there are case studies or even pilot data, for epilepsy there is a lot of data) - brain cancers, migraines, epilepsy, bipolar disorder, dementia, autism, and schizophrenia.
In general, I think it is reasonable that fasting and autophagy should be engaged in on an intermittent basis for all individuals, including heathy ones - I know that if on one particular day I personally eat high carb or low carb, I wake up the next morning in ketosis. That is a sign of metabolic flexibility, which is a positive sign of a healthy metabolism.
Well, that is my opinion. Starchy root vegetables and fruit are good sources of nutrients and in general less expensive than good quality meat, though perhaps not less expensive or easier to store than than good quality fat, calorie for calorie. The nutrients in starch tend to be somewhat different than the ones in fat. I find them pleasurable to eat, personally, and my kids certainly prefer the starch and fruit to just fat, green leafy vegetables, and meat. Perhaps they would truly want mountains of candy and chocolate and their preferences shouldn't guide our health speculations… well, that's my opinion. I simply don't think there is enough evidence to suggest that zero carb diets are optimal for everyone for longevity and health, either from an experimental perspective or from a common sense, physiologic perspective.
Tuesday, November 22, 2011
Soda Begets Zombies
Okay, not likely. But the sugary variety might well be causing depression in those vulnerable to fructose malabsorption. Have a look at my previous post on the subject.
Today I have a mere observational study that adds to a pile of evidence that soda ain't the best thing in the world to be drinking, behaviorally speaking. "The Twinkie Defense: the relationship between carbonated non-diet soft drinks and violence perpetration among Boston high school students."
Here's an appropriate song (right click in new tab to open): Kiss With a Fist
Some bad news about behavior and soda, associatively speaking: In Norwegian adolescents, soda consumption correlated with poor mental health. Among American college students, those who drank more soda were less likely to be social, less able to understand emotional cues, and more likely to favor individualism (is that bad?). There are several reasons soda might cause problems - the sugar could lead to a low blood sugar "crash" which is associated with violence (as I discussed in this post). In addition, soda is a pretty poor source of nutrition other than straight-up calories, so if it replaces more nutritious food in the diet, big soda-drinkers could end up with micronutrient deficiencies. And yeah, micronutrient deficiencies could lead to more violence. No one measured if anyone was a fructose malabsorber.
The experimental design of the Boston study was pretty simple - Boston public high school students were randomly selected and asked to answer a survey. Those who answered that they drank five or more cans of non-diet soda every week comprised 30% of the sample. They controlled for a bunch of covariates (but I can think of several million more). Alcohol, age, gender, race, sleep, smoking, family dinners.
Heavy soda drinkers had similar BMIs to less heavy soda drinkers, and were no more likely to have less than 6 hours sleep. White, Black, and Hispanic kids are all equally likely to be heavy soda drinkers, but Asians were significantly less likely to be quaffing 5 or more cans a week.
Heavy soda users were far more likely to smoke or drink alcohol, and were far more likely to carry around a knife, have been violent with a sibling, a date, or another young person. When the sample was split into 4 quartiles rather than two, the violence link remained linear, suggesting a dose response relationship.
And that's pretty much it. A rather limited self-report study with some statistical crunching, no causal relationship can be inferred; though there are some sensible physiologic explanations as to why soda could make you knife your sister, it isn't proven here. Brain-eating was not examined.
More posts this week! I need to answer js290 regarding the whole linear glucose thing, and I figured it would warrant a short post rather than a comment. Jamie has sent me a few papers, and I pulled some reviews on inflammation, atopy, and behavior.
Today I have a mere observational study that adds to a pile of evidence that soda ain't the best thing in the world to be drinking, behaviorally speaking. "The Twinkie Defense: the relationship between carbonated non-diet soft drinks and violence perpetration among Boston high school students."
Here's an appropriate song (right click in new tab to open): Kiss With a Fist
Some bad news about behavior and soda, associatively speaking: In Norwegian adolescents, soda consumption correlated with poor mental health. Among American college students, those who drank more soda were less likely to be social, less able to understand emotional cues, and more likely to favor individualism (is that bad?). There are several reasons soda might cause problems - the sugar could lead to a low blood sugar "crash" which is associated with violence (as I discussed in this post). In addition, soda is a pretty poor source of nutrition other than straight-up calories, so if it replaces more nutritious food in the diet, big soda-drinkers could end up with micronutrient deficiencies. And yeah, micronutrient deficiencies could lead to more violence. No one measured if anyone was a fructose malabsorber.
The experimental design of the Boston study was pretty simple - Boston public high school students were randomly selected and asked to answer a survey. Those who answered that they drank five or more cans of non-diet soda every week comprised 30% of the sample. They controlled for a bunch of covariates (but I can think of several million more). Alcohol, age, gender, race, sleep, smoking, family dinners.
Heavy soda drinkers had similar BMIs to less heavy soda drinkers, and were no more likely to have less than 6 hours sleep. White, Black, and Hispanic kids are all equally likely to be heavy soda drinkers, but Asians were significantly less likely to be quaffing 5 or more cans a week.
Heavy soda users were far more likely to smoke or drink alcohol, and were far more likely to carry around a knife, have been violent with a sibling, a date, or another young person. When the sample was split into 4 quartiles rather than two, the violence link remained linear, suggesting a dose response relationship.
And that's pretty much it. A rather limited self-report study with some statistical crunching, no causal relationship can be inferred; though there are some sensible physiologic explanations as to why soda could make you knife your sister, it isn't proven here. Brain-eating was not examined.
More posts this week! I need to answer js290 regarding the whole linear glucose thing, and I figured it would warrant a short post rather than a comment. Jamie has sent me a few papers, and I pulled some reviews on inflammation, atopy, and behavior.
Saturday, November 19, 2011
Handel and the Biology of Allergy, Atopy, and Suicide
With respect to classical music, I'm a much bigger fan of the classical and romantic composers (Mozart, Beethoven and all those Russian guys like Rimsky-Korsakoff) than the earlier baroque composers (such as Bach and Handel). Baroque is beautiful and often awe-inspiring, but too structured for my taste -- like a doily or a stained glass window in a church. Back then gardens were arranged into strict geometric designs. We caged nature. Then pastoralism came into vogue, and we get landscape architecture that was meant to be natural and pleasing rather than quite so civilized, and the music of the time reflects this aesthetic as well. The structure and expectations of the preceding baroque era seemed to squeeze the lyricism out of baroque music, though not the beauty.
But a baroque giant, Handel, wrote the Largo from Xerxes, a selection of music that seems to wrest poetry from rigidity. It's an amazing piece, before its time. A game-changer - who knew Handel could be passionate? According to Wikipedia, Mozart said of Handel, "[He] understands affect better than any of us. When he chooses, he strikes like a thunderbolt." Right click to open in new tab.
We have our biology, our natures. And yet we dare impose the structure of agriculture and pharmacology upon it… with an incomplete understanding, at best, particularly in the brain. Such incomplete understanding will lead seemingly learned folks to suggest that we are all diabetic. (We are not). And that glucose is not a toxin but foods that raise blood sugar levels are toxic (er, what?). I probably should not stick my foot into this one, as I am not a metabolism blogger, but for heaven's sake. Without glucose in the bloodstream we are dead. With too much glucose we are poisoned.
Physiology is all about Goldilocks, the right amounts, and the case that all starches are toxic for the vast majority of people is a very, very poor one. And if fasting glucose and overall levels of circulating glucose are important, the strict low-carber who cheats every once in a while might be in more trouble than the healthy starchy-carb eater who will be more exquisitely insulin-sensitive. As Kurt Harris and Melissa McEwen have noted, there is no evolutionary precedent for lifelong very low carb diets, and plenty of examples of healthy cultures who eat starchy carbs. So with our incomplete understanding of physiology, I feel it is a safer bet to use reasonable precedent rather than a zero-carb theory of an optimal longevity diet as a prescription for most people. Certainly there are likely exceptions - seizures, dementia, the first stage of weight loss, in many folks with diabetes. Personally I think calling starch a poison for the majority of people makes about as much sense as demonizing saturated fat.
So. Back to allergies and suicide. This part of the post is for me, really. I need a spot to look back and see the nitty gritty stuff organized in a way that makes sense to me. Actually, this is the point of the entire blog. My self-taught fellowship in Evolutionary Psychiatry.
In the beginning, there were Th1 and Th2 helper cells. These are soldiers of our immune system, called lymphocytes, with different capabilities and called into action in different circumstances. The call to war comes in the form of the release of inflammatory cytokines. There are a whole soup of these chemosignals, released also primarily by T lymphocytes, mostly named interleukins, which are shortened to IL-1, IL-2, IL-3, etc. etc.
In general - the release of inflammatory cytokines can lead to reduced activities and social interaction, and it can activate the HPA axis which can lead to supernormal responses to stress, which can further ramp up the inflammatory response. Elevated pro-inflammatory cytokines can activate the IDO enzyme, reducing serotonin production (this may explain the link between allergy and suicide). Certain types of Th2 related cytokines also increase insomnia. Allergy, then, does not increase the risk of suicide by making people feel sick, but directly through inflammatory means, leading to people withdrawing from social activities and over-react to stressful situations.
What are some more specific features? Well, proinflammatory cytokines released at the time of the allergic reaction activate the HPA axis - the glucocorticoids and catecholamines cause a suppression of Th1 and a shift to Th2 activity by inhibiting IL-12 and promoting IL-10. The pro-inflammatory cytokines also cause dysfunction of corticosteroid receptors. The Th2 lymphocyte produces IL-4, which can effect serotonin metabolism as well - and IL-4 is known to have more effect in people with some genes than others.
En anglais, we are talking here a direct mechanism by which a certain kind of stress, allergy, can affect the neurochemicals in the brain and therefore behavior, and it seems that some people are genetically more vulnerable to this stress than others. That said, other researchers have postulated that the Th1 cytokines impair the serotonin machinery even more than the Th2 ones… we're back to not too hot, not too cold, not too soft, not too hard. It all has to be just right. And what is just right? Depends on your genes and your epigenetics. Superimposing an emulation of the evolutionary milieu is only a first approximation and a good guess.
But a baroque giant, Handel, wrote the Largo from Xerxes, a selection of music that seems to wrest poetry from rigidity. It's an amazing piece, before its time. A game-changer - who knew Handel could be passionate? According to Wikipedia, Mozart said of Handel, "[He] understands affect better than any of us. When he chooses, he strikes like a thunderbolt." Right click to open in new tab.
We have our biology, our natures. And yet we dare impose the structure of agriculture and pharmacology upon it… with an incomplete understanding, at best, particularly in the brain. Such incomplete understanding will lead seemingly learned folks to suggest that we are all diabetic. (We are not). And that glucose is not a toxin but foods that raise blood sugar levels are toxic (er, what?). I probably should not stick my foot into this one, as I am not a metabolism blogger, but for heaven's sake. Without glucose in the bloodstream we are dead. With too much glucose we are poisoned.
Physiology is all about Goldilocks, the right amounts, and the case that all starches are toxic for the vast majority of people is a very, very poor one. And if fasting glucose and overall levels of circulating glucose are important, the strict low-carber who cheats every once in a while might be in more trouble than the healthy starchy-carb eater who will be more exquisitely insulin-sensitive. As Kurt Harris and Melissa McEwen have noted, there is no evolutionary precedent for lifelong very low carb diets, and plenty of examples of healthy cultures who eat starchy carbs. So with our incomplete understanding of physiology, I feel it is a safer bet to use reasonable precedent rather than a zero-carb theory of an optimal longevity diet as a prescription for most people. Certainly there are likely exceptions - seizures, dementia, the first stage of weight loss, in many folks with diabetes. Personally I think calling starch a poison for the majority of people makes about as much sense as demonizing saturated fat.
So. Back to allergies and suicide. This part of the post is for me, really. I need a spot to look back and see the nitty gritty stuff organized in a way that makes sense to me. Actually, this is the point of the entire blog. My self-taught fellowship in Evolutionary Psychiatry.
In the beginning, there were Th1 and Th2 helper cells. These are soldiers of our immune system, called lymphocytes, with different capabilities and called into action in different circumstances. The call to war comes in the form of the release of inflammatory cytokines. There are a whole soup of these chemosignals, released also primarily by T lymphocytes, mostly named interleukins, which are shortened to IL-1, IL-2, IL-3, etc. etc.
In general - the release of inflammatory cytokines can lead to reduced activities and social interaction, and it can activate the HPA axis which can lead to supernormal responses to stress, which can further ramp up the inflammatory response. Elevated pro-inflammatory cytokines can activate the IDO enzyme, reducing serotonin production (this may explain the link between allergy and suicide). Certain types of Th2 related cytokines also increase insomnia. Allergy, then, does not increase the risk of suicide by making people feel sick, but directly through inflammatory means, leading to people withdrawing from social activities and over-react to stressful situations.
What are some more specific features? Well, proinflammatory cytokines released at the time of the allergic reaction activate the HPA axis - the glucocorticoids and catecholamines cause a suppression of Th1 and a shift to Th2 activity by inhibiting IL-12 and promoting IL-10. The pro-inflammatory cytokines also cause dysfunction of corticosteroid receptors. The Th2 lymphocyte produces IL-4, which can effect serotonin metabolism as well - and IL-4 is known to have more effect in people with some genes than others.
En anglais, we are talking here a direct mechanism by which a certain kind of stress, allergy, can affect the neurochemicals in the brain and therefore behavior, and it seems that some people are genetically more vulnerable to this stress than others. That said, other researchers have postulated that the Th1 cytokines impair the serotonin machinery even more than the Th2 ones… we're back to not too hot, not too cold, not too soft, not too hard. It all has to be just right. And what is just right? Depends on your genes and your epigenetics. Superimposing an emulation of the evolutionary milieu is only a first approximation and a good guess.
Thursday, November 17, 2011
Sniffles and Suicide
Let's revisit the basic premise, my hypothesis we are searching to disprove. Humans are not broken, but we are not optimized for our current environment, whether it be modern stress, modern social structure, modern diet, modern sleep, or modern activity. Perturbations from the homo sapiens "norm" of paleolithic life (minus the few adaptations we have accumulated in the recent years) lead to modern human disease, mental and physical.
In a broad stroke, pathology in the human body is mediated via abnormal immune response - thus autoimmunity and inflammation. This piece of the theory has mounting evidence both for physical and mental health diseases. Inflammation in the brain can lead to disturbances of human behavior - to anxiety, extreme depression, and even suicide.
In a broad stroke, pathology in the human body is mediated via abnormal immune response - thus autoimmunity and inflammation. This piece of the theory has mounting evidence both for physical and mental health diseases. Inflammation in the brain can lead to disturbances of human behavior - to anxiety, extreme depression, and even suicide.
Today an interesting paper newly out in the Journal of Clinical Psychiatry, Suicide and Prescription Rates of Antiallergy Medications: An Ecological Study.
I know. That sort of a title will make any Evolutionary Psychiatrist's ears prick up.
First, though, suicide. With any human condition, sometimes the best place to look for clarity and understanding is Steinbeck, who won the Nobel and Pulitzer prizes for literature. And, like many men of the 20th century, John Steinbeck died of heart disease in his 60s.
He wrote a sympathetic portrayal of a suicidal man in what I consider to be his best work, East of Eden:
On another sheet he wrote, "Dear Will, No matter what you youself may think -- please help me now. For Mother's sake -- please. I was killed by a horse -- thrown and kicked in the head -- Please! Your brother, Tom."
...In his bedroom he broke open a new box of shells and put one of them in the cylinder of his well-called Smith and Wessen .38 and he set the loaded chamber one space to the left of the firing pin. His horse standing sleepily near the fence came to his whistle and stood drowsing while he saddled up.
It was three o’clock in the morning when he dropped the letters in the post-office at King City and mounted and turned his horse south toward the unproductive hills of the old Hamilton place.
He was a gallant gentlemen.
Certainly many suicides are planned -- often if family members get letters or phone calls ahead of time, it can be prevented. Sometimes though, suicidal urges come on in an unbearable wave, and if someone has access to lethal means (typically firearms, hanging, or jumping), the urge becomes deadly. A very interesting examination of people who survived jumping from the Golden Gate Bridge showed that only 10% of people who survived went on to complete suicide later. Most of the time, the urge to kill oneself is impulsive. Often there are biological markers - increased inflammation and low serotonin, among others.
Allergies, of course, are very common. And if suicide is in part an inflammatory issue, then one would suspect that people inflamed with allergies are more likely to commit suicide. There are, indeed, correlations between allergy and suicide. And while I tend to think of spring and fall as suicide seasons (spring in particular) due to rapid change of sunlight during those times, spring and fall are also allergy seasons, with spring being the peak of hospitalizations for those with severe allergy problems. It turns out that the link between suicide and seasons (particularly the springtime) is stronger in those with allergies.
The authors of the allergy medicine and suicide paper had an interesting premise. They looked at the theory between the connectedness of allergy and suicide in a very biological way. They looked a data showing increased gene expression of cytokines that mediate the activity of a of a certain type of immune cell, Th2 (T-helper cells type 2) in the prefrontal cortex of postmortem suicide victims. Then they looked at the main treatments for allergies/asthma - antihistamines (like claritin) and intranasal steroids (like rhinocort). An antihistamine won't change Th2 helper cell activity. A steroid will decrease it via direct means. The authors went county by county in the US comparing non-sedating antihistamine prescription data and inhaled corticosteroid data with reported suicides, antidepressant prescription data, availability of psychiatrists, urban vs. rural, demographics, within-country vs. intra-county and crunched numbers. And man, they crunched numbers to a degree that is way beyond my ken. They used logarithms and differential equations and basically took the huge amount of data and crunched the heck out of it. I can't speak to the veracity of the crunchedness as I am no statistician. It sounds reasonable but any mathematical skeptic who wants to look at the paper and pull it apart, feel free to get in touch.
They found that antihistamine prescriptions (and they excluded sedating antihistamines such benadryl or vistaril which are often prescribed for sleep, not allergies) were positively correlated with suicide rates (p=.0001) and that intranasal corticosteroids prescription rates were inversely associated with suicide rates (p=.0004). So if prescriptions for inhaled corticosteroids were to increase by 1%, the suicide rate should decrease by 0.16% (0.04 suicides per 100,000 people). The use of decongestants was neutral with respect to suicide risk.
The discussion in the paper is complex, noting that systemic steroids are known to cause problematic psychiatric side effects (which is certainly true) but that intranasal steroids (for the most part) seem to bypass this problem and have minimal systemic effects, merely decreasing inflammation in the nose, where it counts. Some data suggesting that intranasal steroids do cause jitteriness, anxiety, agitation, insomnia, and depression in certain people makes the findings of this study even more interesting. Could Th2 suppression in certain cases more than compensate for the negative psychological effects of nasal corticosteroids, at least with respect to suicide?
In East of Eden, Tom knew what his mother felt about suicide:
[She] had a strong distaste for suicide feeling that it combined three things of which she strongly disapproved -- bad manners, cowardice, and sin.
Inflammation is, indeed, unmannerly, but I think we go too far to call it cowardice or sin. We should look closer, look further, and truly delineate this pathology. Suicide is the 10th leading cause of death in the world, and the 11th in the United States. Inflammation is the number one cause of death in the modern world.
Sunday, November 13, 2011
Is Postpartum Psychosis an Autoimmune Disease?
Here's an article for the "everything is connected" file. Also for "yes, psychiatric disease has biologic underpinnings and is medical illness" file. Also the "inflammation in the wrong place at the wrong time is super-bad" file. And it may be of interest to anyone who has had symptoms of autoimmune disease helped by an anti-inflammatory (paleo-type) diet.
Postpartum psychosis is rare and scary. About 1 in 1000 women become psychotic in the first months after having a baby (though anything up to 12 months after is considered "postpartum" the greatest risk is in the first month). The most typical presentation is one of manic psychosis, with prominent insomnia, irritability, and delusions of grandeur. However, some women will also be depressed and be delusional and suicidal, or even with delusions that lead a women to kill her baby.
Not surprisingly, a prior diagnosis of bipolar disorder is the greatest risk factor for developing postpartum psychosis. However, most women with postpartum psychosis have no history of psychiatric illness at all (1). Often the illness requires hospitalization, and though there are no "consensus treatment guidelines," in almost all cases benzodiazepines (sedative, anti-anxiety meds, such as lorazepam) are used to help stabilize sleep-wake cycles, and in most cases antipsychotics are also used, typically with good effect. If those aren't helping, lithium is added.
Here's another bit of info about pregnancy. The fetus is obviously genetically different than mom, so women develop a depressed immune system during pregnancy, in order to protect the growing beastie from mom's antibodies and killer cells. This is why I was told to studiously avoid unpasturized cheese and raw eggs and deli meat during pregnancy, and why healthy women in the third trimester are much more likely to develop severe complications and die from the flu than women who are not pregnant.
It is well known that in women with a dysfunctional immune system (the autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and autoimmune thyroiditis), the autoimmune symptoms are generally greatly ameliorated during pregnancy. However, this time of relatively low autoimmune symptoms is followed in the post-partum period by a "rebound" with greatly increased symptoms and greater autoantibody titers measured in the serum.
So is post-partum psychosis a symptom of autoimmune disease? Specifically autoimmune thyroid disease, as thyroid disease (both hyper- and hypothyroidism) is well known to cause psychiatric symptoms, even psychosis?
Well, those societies with socialized medicine were able to gather data in such a way as to start to give us an answer to that question. In the Netherlands, all the women in a certain area of the country who developed post-partum psychosis and ended up in the hospital were checked for autoimmune thyroid antibodies and thyroid function upon admission to the hospital. A larger control group of other post-partum women were also checked. Critically, women who were medicated at admission (particularly with lithium) were excluded from the study, as lithium is known to depress thyroid function. All women with a previous history of thyroid disease, bipolar disorder, schizophrenia, or psychosis were excluded. That left a group of 29 women with new-onset post-partum psychosis and 117 controls.
Here is what the researchers found. 5% of post-partum women in the control group had measurable autoimmune thyroid autoantibodies at 4 weeks after delivery, a sign of autoimmune thyroid disease. This is comparable to surveys of a general population of women in the Netherlands. None of them had measurable abnormalities in thyroid function or any symptoms. In contrast, 19% of the post-partum psychosis patients had measurable thyroid autoantibodies at admission (again, prior to receiving any lithium or antipsychotic medication treatment), and half of those women also had measurable thyroid abnormalities. In the following 9 months, 67% of the postpartum psychosis women with autoimmune thyroid antibodies went on to develop measurable thyroid problems (abnormal TSH or free thyroxine). None of the control women did. The odds ratios for these findings were all >2, some as large as 9, which is quite significant, especially considering the size of the sample).
Even though patients with previous bipolar disorder were excluded from this study, the researchers note that the 19% prevalence of autoimmune thyroid antibodies in these psychotic women is similar to the prevalence in women with bipolar disorder (2). And, to really get your noggins going, twin studies of bipolar disorder show that the presence of autoimmune thyroid antibodies are correlated not only to the illness itself, but to the genetic vulnerability to the illness (3).
The researchers in this study strongly recommended that all women with postpartum psychosis be monitored for thyroperoxidase antibodies and thyroid function abnormalities, and furthermore that all women at high risk for postpartum psychosis be monitored before and throughout pregnancy and the postpartum period. Though this was a small observational study, the advice seems very reasonable.
And, as always, we find that "post-partum psychosis" like many psychiatric symptoms is the equivalent of a fever - signaling underlying abnormalities, but not always caused by the flu. Sometimes fevers are caused by different bugs, or cancer, or autoimmune disease. Differentiating the underlying pathology will go a long way to informing our treatments (and helping in prevention) in the future.
Psychiatrists and other doctors reading this article will be interested in one directed more to healthcare professionals about the same study at the MGH Center for Women's Mental Health blog by Ruta Nonacs, MD PhD. Thanks to Dr. Trevisan for the link to the blog post!
Postpartum psychosis is rare and scary. About 1 in 1000 women become psychotic in the first months after having a baby (though anything up to 12 months after is considered "postpartum" the greatest risk is in the first month). The most typical presentation is one of manic psychosis, with prominent insomnia, irritability, and delusions of grandeur. However, some women will also be depressed and be delusional and suicidal, or even with delusions that lead a women to kill her baby.
Not surprisingly, a prior diagnosis of bipolar disorder is the greatest risk factor for developing postpartum psychosis. However, most women with postpartum psychosis have no history of psychiatric illness at all (1). Often the illness requires hospitalization, and though there are no "consensus treatment guidelines," in almost all cases benzodiazepines (sedative, anti-anxiety meds, such as lorazepam) are used to help stabilize sleep-wake cycles, and in most cases antipsychotics are also used, typically with good effect. If those aren't helping, lithium is added.
Here's another bit of info about pregnancy. The fetus is obviously genetically different than mom, so women develop a depressed immune system during pregnancy, in order to protect the growing beastie from mom's antibodies and killer cells. This is why I was told to studiously avoid unpasturized cheese and raw eggs and deli meat during pregnancy, and why healthy women in the third trimester are much more likely to develop severe complications and die from the flu than women who are not pregnant.
It is well known that in women with a dysfunctional immune system (the autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and autoimmune thyroiditis), the autoimmune symptoms are generally greatly ameliorated during pregnancy. However, this time of relatively low autoimmune symptoms is followed in the post-partum period by a "rebound" with greatly increased symptoms and greater autoantibody titers measured in the serum.
So is post-partum psychosis a symptom of autoimmune disease? Specifically autoimmune thyroid disease, as thyroid disease (both hyper- and hypothyroidism) is well known to cause psychiatric symptoms, even psychosis?
Well, those societies with socialized medicine were able to gather data in such a way as to start to give us an answer to that question. In the Netherlands, all the women in a certain area of the country who developed post-partum psychosis and ended up in the hospital were checked for autoimmune thyroid antibodies and thyroid function upon admission to the hospital. A larger control group of other post-partum women were also checked. Critically, women who were medicated at admission (particularly with lithium) were excluded from the study, as lithium is known to depress thyroid function. All women with a previous history of thyroid disease, bipolar disorder, schizophrenia, or psychosis were excluded. That left a group of 29 women with new-onset post-partum psychosis and 117 controls.
Here is what the researchers found. 5% of post-partum women in the control group had measurable autoimmune thyroid autoantibodies at 4 weeks after delivery, a sign of autoimmune thyroid disease. This is comparable to surveys of a general population of women in the Netherlands. None of them had measurable abnormalities in thyroid function or any symptoms. In contrast, 19% of the post-partum psychosis patients had measurable thyroid autoantibodies at admission (again, prior to receiving any lithium or antipsychotic medication treatment), and half of those women also had measurable thyroid abnormalities. In the following 9 months, 67% of the postpartum psychosis women with autoimmune thyroid antibodies went on to develop measurable thyroid problems (abnormal TSH or free thyroxine). None of the control women did. The odds ratios for these findings were all >2, some as large as 9, which is quite significant, especially considering the size of the sample).
Even though patients with previous bipolar disorder were excluded from this study, the researchers note that the 19% prevalence of autoimmune thyroid antibodies in these psychotic women is similar to the prevalence in women with bipolar disorder (2). And, to really get your noggins going, twin studies of bipolar disorder show that the presence of autoimmune thyroid antibodies are correlated not only to the illness itself, but to the genetic vulnerability to the illness (3).
The researchers in this study strongly recommended that all women with postpartum psychosis be monitored for thyroperoxidase antibodies and thyroid function abnormalities, and furthermore that all women at high risk for postpartum psychosis be monitored before and throughout pregnancy and the postpartum period. Though this was a small observational study, the advice seems very reasonable.
And, as always, we find that "post-partum psychosis" like many psychiatric symptoms is the equivalent of a fever - signaling underlying abnormalities, but not always caused by the flu. Sometimes fevers are caused by different bugs, or cancer, or autoimmune disease. Differentiating the underlying pathology will go a long way to informing our treatments (and helping in prevention) in the future.
Psychiatrists and other doctors reading this article will be interested in one directed more to healthcare professionals about the same study at the MGH Center for Women's Mental Health blog by Ruta Nonacs, MD PhD. Thanks to Dr. Trevisan for the link to the blog post!
Friday, November 11, 2011
Evolutionary Psychiatry and Bipolar Disorder
A couple of papers came to my attention this week that relate to what I consider "real" evolutionary psychiatry. That is, what are some evolutionary reasons we might have genes that make us vulnerable to psychiatric disorders. The "real" evolutionary psychology academics consider this discussion to be "Abnormal Psychology," and like all evolutionary psychology, it is somewhat controversial. I actually don't think about the disorders much as evolving in an evolutionary light… I tend to think in terms of the human body and gut and neurons working outside design specs, thus breaking down (that is "my" version of evolutionary psychiatry). But the overlap between one ev psych and another deserves some scrutiny, because certainly I can make the case (and often do, to patients, particularly those with bipolar and ADHD and OCD) that there are elements of these disorders that are quite adaptive to certain situations, as long as the maladaptive parts don't derail everything.
Part of my major hypothesis is that the industrial/digital age and processed, low-nutrient food has brought out more severe and different phenotypes of underlying vulnerabilities, and has also brought out seemingly new illnesses ("atypical depression"). Thus a less destructive phenotype (a mildly paranoid schizotypal person, for example, who will be more creative than the average person, as compared to full-blown schizophrenia, which impairs functioning to a terrible extent) will persist in the population due to selective advantage for certain traits.
My only previous article on "real" evolutionary psychiatry can be found here: The Creative Advantage.
Well. It is fitting the first of the two papers today comes from Medical Hypothesis. Melissa McEwen sent it to me - I think she likes that journal because it is crazy and it makes her laugh. (Here is advice for those aspiring to be published there: The purpose of Medical Hypotheses is to publish interesting theoretical papers. The journal will consider radical, speculative and non-mainstream scientific ideas provided they are coherently expressed.)
I have no publications, myself, though I have assisted in some research efforts. My mentor would like me to cobble something together from all the research I've done for the blog on affective disorders, or something. I never did fancy myself much of an academic… thus never felt the motivation to write anything boring enough to be published in a journal ;-)… however, it would certainly add to my street cred. I don't know that I can write the exotic papers for Medical Hypothesis, however (Melissa sent me a paper previously about some sort of reptile origin theory of illness? I can't remember, but it was hysterical, and it must have slipped through part of the editorial process as it was also mostly incoherent). Back to evolutionary psychiatry!
Evolutionary origin of bipolar disorder - revised (EOBD-R) is the paper in question, by one Julia A. Sherman of Madison, Wisconsin. A quick google search brings up her original EOBD (sans R) from 2002. And as much as I make light of Medical Hypothesis, I do have to admire the originality of the paper, noting that it is wildly speculative and the basic premise is most likely incorrect.
Ms. Sherman connects the dots between the circadian rhythm issues and vulnerability to bipolar disorder (manic episodes are known to peak in the spring time, when the light increases exponentially day by day in extremely northern or southern latitudes.) In a nutshell, the EOBD suggests that bipolar disorder developed as an adaptive trait in the northern temperate zones which had more extreme winters during the ice age. If you were hypomanic all spring and summer, you got a lot of stuff done, and then you could slow down and "hibernate" (be depressed) during the winter and not use much energy. The "R" or revision in question actually brings in the interesting bit of Neanderthal DNA that all of us non-San Bushmen (or otherwise directly derived from Africa without side-stepping through Europe or Asia and coming up close and very personal with other hominids) seem to have. Ms. Sherman thinks that bipolar disorder is a Neanderthal trait.
Hmmm. She brings in the observations of a German psychiatrist from the early 20th century, E. Kretchmer, who noted that folks with bipolar disorder tended to be of a certain "pyknic" constitutional type. They have a "thick trunk, relatively short limbs, and a big head on a short, thick neck." Apparently, several other researchers in the early 20th century, when they were really into measuring heads and body sizes and making silly claims based on the measurements found that manic-depressive patients were more likely to be pyknic (endomorphs), and schizophrenics were more likely to be "leptosomic" (ectomorphs). A much newer study in 2003 also confirmed this finding. Sherman believes it is striking that Neanderthals are also described as having big bellies and short limbs. Interesting. In addition, people of African descent apparently have lower incidence of bipolar disorder in some studies Sherman cites. However, there is no reliable data among truly purely African populations such as the San.
There is more to the paper, but I hit the highlights. I'm not entirely sure what to think. There is no question that bipolar disorder has a seasonal component and that light and dark therapies can be useful. Hypomania, with the extended bursts of drive, energy, and creativity can also be very adaptive. And one can imagine being moderately depressed during a cold, dark winter might keep a small tribe of Neanderthal out of each other's hair, when there might have been nothing much to do anyway. I think the pyknik bit is a little ridiculous - as we know, actually, both schizophrenia and bipolar disorder are related to metabolic syndrome, even in people who have never been on medicines. I also would bet a poodle that there are San bushmen with some bipolar disorder out there, but symptoms might be attenuated by their latitude and hunter-gatherer lifestyle with plenty of socialization and exercise (though they do like those omega 6-filled mongongo nuts), according to my own wildly speculative theorizing…
The second paper is far less... imaginative and was published in the much more staid Journal of Affective Disorders. Creativity and affective temperaments in non-clinical professional artists: An empirical psychometric investigation. These researchers looked at 152 undergraduates in art school (or other creative majors) vs. 152 undergraduates who were in majors predicted to lead to professions "mostly requiring the application of learned rules" (like accounting, I suspect). The students were tested with several standard measures to detect subclinical and clinical manifestation of cyclothymia (a mild variation of bipolar disorder), and also other scales of general health and demographic data. I don't think it will surprise anyone to know that the creative students were significantly more likely to score into the cyclothymic range on these scales.
An interesting quote from the paper:
So it appears that bipolar disorder is linked to creativity, which may have an adaptive advantage. I don't think that is particularly controversial, but it is nice to see more studies on the subject. Now were Neanderthals more creative than homo sapiens? At least in the springtime? That might help Julia Sherman's hypothesis!
Edited to add - a Neanderthal winter love song? By Primitive Radio Gods (right click to open in new tab).
Part of my major hypothesis is that the industrial/digital age and processed, low-nutrient food has brought out more severe and different phenotypes of underlying vulnerabilities, and has also brought out seemingly new illnesses ("atypical depression"). Thus a less destructive phenotype (a mildly paranoid schizotypal person, for example, who will be more creative than the average person, as compared to full-blown schizophrenia, which impairs functioning to a terrible extent) will persist in the population due to selective advantage for certain traits.
My only previous article on "real" evolutionary psychiatry can be found here: The Creative Advantage.
Well. It is fitting the first of the two papers today comes from Medical Hypothesis. Melissa McEwen sent it to me - I think she likes that journal because it is crazy and it makes her laugh. (Here is advice for those aspiring to be published there: The purpose of Medical Hypotheses is to publish interesting theoretical papers. The journal will consider radical, speculative and non-mainstream scientific ideas provided they are coherently expressed.)
I have no publications, myself, though I have assisted in some research efforts. My mentor would like me to cobble something together from all the research I've done for the blog on affective disorders, or something. I never did fancy myself much of an academic… thus never felt the motivation to write anything boring enough to be published in a journal ;-)… however, it would certainly add to my street cred. I don't know that I can write the exotic papers for Medical Hypothesis, however (Melissa sent me a paper previously about some sort of reptile origin theory of illness? I can't remember, but it was hysterical, and it must have slipped through part of the editorial process as it was also mostly incoherent). Back to evolutionary psychiatry!
Evolutionary origin of bipolar disorder - revised (EOBD-R) is the paper in question, by one Julia A. Sherman of Madison, Wisconsin. A quick google search brings up her original EOBD (sans R) from 2002. And as much as I make light of Medical Hypothesis, I do have to admire the originality of the paper, noting that it is wildly speculative and the basic premise is most likely incorrect.
Ms. Sherman connects the dots between the circadian rhythm issues and vulnerability to bipolar disorder (manic episodes are known to peak in the spring time, when the light increases exponentially day by day in extremely northern or southern latitudes.) In a nutshell, the EOBD suggests that bipolar disorder developed as an adaptive trait in the northern temperate zones which had more extreme winters during the ice age. If you were hypomanic all spring and summer, you got a lot of stuff done, and then you could slow down and "hibernate" (be depressed) during the winter and not use much energy. The "R" or revision in question actually brings in the interesting bit of Neanderthal DNA that all of us non-San Bushmen (or otherwise directly derived from Africa without side-stepping through Europe or Asia and coming up close and very personal with other hominids) seem to have. Ms. Sherman thinks that bipolar disorder is a Neanderthal trait.
Hmmm. She brings in the observations of a German psychiatrist from the early 20th century, E. Kretchmer, who noted that folks with bipolar disorder tended to be of a certain "pyknic" constitutional type. They have a "thick trunk, relatively short limbs, and a big head on a short, thick neck." Apparently, several other researchers in the early 20th century, when they were really into measuring heads and body sizes and making silly claims based on the measurements found that manic-depressive patients were more likely to be pyknic (endomorphs), and schizophrenics were more likely to be "leptosomic" (ectomorphs). A much newer study in 2003 also confirmed this finding. Sherman believes it is striking that Neanderthals are also described as having big bellies and short limbs. Interesting. In addition, people of African descent apparently have lower incidence of bipolar disorder in some studies Sherman cites. However, there is no reliable data among truly purely African populations such as the San.
There is more to the paper, but I hit the highlights. I'm not entirely sure what to think. There is no question that bipolar disorder has a seasonal component and that light and dark therapies can be useful. Hypomania, with the extended bursts of drive, energy, and creativity can also be very adaptive. And one can imagine being moderately depressed during a cold, dark winter might keep a small tribe of Neanderthal out of each other's hair, when there might have been nothing much to do anyway. I think the pyknik bit is a little ridiculous - as we know, actually, both schizophrenia and bipolar disorder are related to metabolic syndrome, even in people who have never been on medicines. I also would bet a poodle that there are San bushmen with some bipolar disorder out there, but symptoms might be attenuated by their latitude and hunter-gatherer lifestyle with plenty of socialization and exercise (though they do like those omega 6-filled mongongo nuts), according to my own wildly speculative theorizing…
The second paper is far less... imaginative and was published in the much more staid Journal of Affective Disorders. Creativity and affective temperaments in non-clinical professional artists: An empirical psychometric investigation. These researchers looked at 152 undergraduates in art school (or other creative majors) vs. 152 undergraduates who were in majors predicted to lead to professions "mostly requiring the application of learned rules" (like accounting, I suspect). The students were tested with several standard measures to detect subclinical and clinical manifestation of cyclothymia (a mild variation of bipolar disorder), and also other scales of general health and demographic data. I don't think it will surprise anyone to know that the creative students were significantly more likely to score into the cyclothymic range on these scales.
An interesting quote from the paper:
Positive mood, and happiness in particular, was postulated to fuel creativity. Enhanced positive affect is a feature of both hypomania and mania, which are core symptoms of bipolar disorder and may predispose people within the manic-depression/bipolar disorder spectrum to creativity. By contrast, postulated that depression might provide fresh insights which can be executed into the artistic oeuvre during the energized phases of cyclothymia.
So it appears that bipolar disorder is linked to creativity, which may have an adaptive advantage. I don't think that is particularly controversial, but it is nice to see more studies on the subject. Now were Neanderthals more creative than homo sapiens? At least in the springtime? That might help Julia Sherman's hypothesis!
Edited to add - a Neanderthal winter love song? By Primitive Radio Gods (right click to open in new tab).
Monday, November 7, 2011
Is Some Psychiatric Disease a Manifestation of Lyme Disease?
Hello there! I’ve been offline at home for the past week, ever since the big snowstorm that came through the northeast in late October. The wet, heavy snow landed on trees that still had their leaves, leading to incredible amounts of damage and fallen limbs. That night as the snow fell, we listened to branches cracking and snapping and falling and saw arcing electricity light up the sky as wires were torn down. By morning hundreds of thousands of people were without power, including us — our wires were pulled off the side our house by falling branches. 30 foot tall trees were snapped in half, like toothpicks. (That picture is of the end of our driveway)
On the Friday before the storm I received my order of 60 pounds of grassfed, high quality beef from Paidom Ranch in Texas. On Sunday morning I filled 20 freezer bags full of the fresh snow and stuffed them in the powerless freezers and fridge, so the meat was still nice and frozen even after a few days without power. Without heat and daytime temps in the mid-fifties, it might have been just fine as it was. Halloween was put off until the following Friday night, though the neighborhood is still a mess. Power came back in two days, but our wires were still on the ground, caught in a turf war between the utility company, local electricians, and the town inspector. Back in Texas where I’m from, the utility company is responsible up to the meter — here there is something of a gray area between the property line and the meter, which would be okay, except you are at the mercy of the utility company as to when the power comes on and off so you can repair the lines on your property, leading to the ridiculous situation where we had live wires ready to electrocute anyone unlucky enough to trespass for several days, until the town inspector intervened and made the power company fix the problem.
Well. As I write this article, we are still offline at the house with respect to cable TV, landline phone, and internet (so-called bundled services are so much fun!). I’m hoping it will be back in the next several days so I can publish — fortunately the smartphone works for email and the like.
But enough of our tale of first world woe, except the disease I am about to discuss has long been maligned due to the attention it has received affecting wealthy Connecticut kids. However, I’ve seen many afflicted folks in my practice here in Massachusetts, and several family members and friends have been treated for it. So I take Lyme Disease, or Borrelia burgdorferi very seriously. Borrelia, along with several other nasty organisms, such as the microbes that cause babesiosis, ehrlichiosis, Rocky Mountain Spotted Fever, and rickettsia, are all spread by dirty tick bites.
(Quick and easy tic repellant for the spring and summer - 2 tbs coconut oil, 1 tbs aloe vera gel, 25 drops gardenia or rose oil, 25 drops lavender oil. The essential oils can be found at Whole Foods. Stir and smear on ankles, wrists, forehead, nape of neck, belly, and anywhere else tics are liable to climb in. Last summer prior to use of this ointment we had 6 tics found on kids and husband (tics and mosquitos do not like me - I am too sour) - afterwards no tics whatsoever. Thanks to @OldSalt72 for the link to the recipe)
Lyme disease is endemic to the area in which I now live, and if transmitted, can become a multisystem inflammatory disease that can affect the skin, joints, heart, and nervous system. Borrelia burgdorferi is a spirochete gram-negative bacteria in the Treponemataceae family, like the agent that causes syphilis, rather famous for its neurological findings, Treponema palidum.
Syphilis and tuberculosis are known in medicine as the “great imitators,” meaning these infections can be mistaken for many other problems, from psychiatric disorders to heart disease. Lyme disease is very tricky as there are supposedly many false negatives when you check serology. If you have a suspected deer tick attached for more than 24-48 hours here in Massachusetts, you are better off getting an extended antibiotic regimen just in case (for adults, doxycycline, for young kids, amoxicillin), considering the nastiness of the illness if not treated early.
In a paper from 2002, Hajek et al screened for antibodies to Borrelia in 926 Czech psychiatric patients between 1995 and 1999. 884 healthy persons were recruited at the same time from the general healthy population. 36% of the psychiatric patients were positive in at least one antibody class for exposure to Borrelia. Only 18% of the healthy controls were positive. That’s a rip-roaring difference, to put it in scientific terms. Since the psychiatric group was older, statistically, than the healthy group, age-matching was done (statistically), and the results were similar.
An older study in the US showed very low seropositivity in a group of psychiatric patients - however, the general population in the US has much less exposure to Lyme (1% as opposed to a much higher percentage of folks in Europe), and the assay used to detect the antibodies was rather old-fashioned in the older study. (Western blot in 2002 was gold standard, ELISA a close second, and flourescent immunoassay was used in the older US study).
The first immune response to Borrelia will be IgM antibodies, which peaks 4-6 weeks after infection, followed by the more specific IgG response, which peaks at 6 weeks, but like IgM can persist for months to years. Antibodies circulating in immune complexes are likely to signify ongoing disease activity.
If Borrelia burgdorfi is related to psychiatric problems, there are two main mechanisms which could be responsible. Patients vulnerable to psychiatric disease may also be more susceptible to Lyme or neurotoxic effects due to genetic or other factors. Second, Borrelia may cause psychiatric symptoms, which is the most parsimonious explanation. PCR analysis and other advanced methods ought to be employed in the future, and more surveys run on the population to better clarify this phenomenon.
In short, Borrelia burgdorfi is one of those suspicious, long-term, nasty and sneaky pathogens that could contribute to inflammation and issues in the brain for years or decades. It may be well one of the many inflammatory activators that are increasing our psychiatric diagoses in recent times, along with diet, lack of sleep, lack of sunshine, increased stress, and lack of exercise. The problem with Lyme is that many people who seem to have symptoms (and even those with known tic bites and classic rashes) do not test as positive. But is it really a solution to give everyone a course of doxycycline? This issue is my question with respect to any infection that may have neuropsychiatric symptoms - we need more data. In the mean time, I like anti-inflammatory, nutrient rich diets and plenty of sleep, sunshine and stress reduction.
Sunday, November 6, 2011
Offline
Hi all! A snowstorm took out my
home Internet service a week ago, and it is still not repaired. I have a post written for when service is restored, but in the mean time, be sure to check out the "map" at the upper right for some pertinent archives.
- Posted using BlogPress from my iPhone
home Internet service a week ago, and it is still not repaired. I have a post written for when service is restored, but in the mean time, be sure to check out the "map" at the upper right for some pertinent archives.
- Posted using BlogPress from my iPhone
Deer Hunting, Part I
It is deer season in North Dakota, and on opening day, I went out hunting with four other men. Between the five or us, we got three deer, two does and a buck. Unfortunately, I was one of the two that did not shoot something. We simply ran out of time, as it got dark. I guess that is what next weekend is for! We saw two or three dozen deer during the day, and only two or three other hunters. That is the benefit of living in a geographically large state, with a very small population (670,000 people, about one third of whom live in Fargo).
It was a very good experience. After each kill, we had to field dress the carcass and carry it back to the truck. Since hunting was only allowed on opening day after 12 noon, and since it got dark at about 6:30 p.m., that was not a bad record. Each kill took time to deal with the dead animal. We cleaned the last one in the dark, using flashlights, and could hear the coyotes baying at the moon. I suspect they fed well that night, on all the dear guts left from the field dressing of each kill. This was my first time hunting (after going Paleo, I thought it would be a good thing to kill some of my own meat) and I expect to make it an annual event.
I grew up in Utah, and deer hunting there is very different, as two of my brothers who still live there assure me. For one thing, the deer in Utah are mule deer, and are considerably larger than the white tail deer we hunt in central/eastern North Dakota. But the biggest difference was that North Dakota is basically flat: no lugging deer carcasses up and down mountains. Lugging them back to the truck across flat terrain was hard enough. It gave me new respect for Mark Sisson's advice to move and lift heavy things on a regular basis.
Assuming I get my deer next week, I am very tempted to take up bow hunting as well. There is something deeply primal about stalking a deer with a bow, then having to chase the animal down after it is wounded.
The only problem with North Dakota deer: I am pretty sure these deer spent much of the last two months gorging on corn and other crops, as this is an agricultural state. So much for grass-fed deer.
It was a very good experience. After each kill, we had to field dress the carcass and carry it back to the truck. Since hunting was only allowed on opening day after 12 noon, and since it got dark at about 6:30 p.m., that was not a bad record. Each kill took time to deal with the dead animal. We cleaned the last one in the dark, using flashlights, and could hear the coyotes baying at the moon. I suspect they fed well that night, on all the dear guts left from the field dressing of each kill. This was my first time hunting (after going Paleo, I thought it would be a good thing to kill some of my own meat) and I expect to make it an annual event.
I grew up in Utah, and deer hunting there is very different, as two of my brothers who still live there assure me. For one thing, the deer in Utah are mule deer, and are considerably larger than the white tail deer we hunt in central/eastern North Dakota. But the biggest difference was that North Dakota is basically flat: no lugging deer carcasses up and down mountains. Lugging them back to the truck across flat terrain was hard enough. It gave me new respect for Mark Sisson's advice to move and lift heavy things on a regular basis.
Assuming I get my deer next week, I am very tempted to take up bow hunting as well. There is something deeply primal about stalking a deer with a bow, then having to chase the animal down after it is wounded.
The only problem with North Dakota deer: I am pretty sure these deer spent much of the last two months gorging on corn and other crops, as this is an agricultural state. So much for grass-fed deer.
Thursday, November 3, 2011
Credibility and the "Safe Starch" Debate
"It is difficult to get a man to understand something, when his
salary depends upon his not understanding it." --Upton Sinclair
Are all carbohydrates bad? No. In a post today on Robb Wolf's blog about meat and potatoes, Matt Lentzner said: "Judging a food solely by its macronutrient composition is stupid. It’s hard to believe it has taken us 50 years to figure that out. We have good fats (saturated and omega-3’s) and bad fats (omega-6’s), good carbs (starch) and bad carbs (fructose), good proteins (meat) and bad proteins (gluten). It’s the quality of the macronutrient, not it’s classification, that makes it good or bad."
I agree with Lentzner that it is quality, not classification, and that it is stupid to judge a food solely by its macronutrient composition. I didn't always believe this, but I do now.
Why is it so hard to understand that there might be "good carbs," or, in the parlance of the debate du jour, "safe starches?" Why is the idea of a "safe starch" so threatening to so many people? The whole safe starch debate was really surprising to me, until I stumbled across the quote above by Upton Sinclair. Then, all of a sudden, a light went on.
It appears to me that the major proponents of the "all carbs are bad" school of thought (I won't name names, but it isn't too hard to do) all make a good portion of their livelihood (if not all of their livelihood) from promoting this idea. It also appears to me that the major defenders of the safe starch debate, Paul and Shou-Ching Jaminet, do not make their livelihood promoting the Perfect Health Diet, so they are more flexible in and open to accepting new information. The same is true with Kurt Harris and his Archevore diet and for others. Their livelihood does not depend on defending a certain belief or viewpoint at all costs, so they are able to go against the grain when strong evidence is available.
The idea that there may be "safe starches" (good carbs) must be incredibly threatening to those whose livelihoods depend on not believing this idea. So they reflexively defend it at all costs. As a professor at a state-sponsored university, I do the same thing when people suggest cutting state funds for higher education. I am not immune to the impulse. Even if I intellectually understand the arguments about out-of-control higher education spending, I am viscerally against them, as my livelihood is at stake. So I am not throwing stones, just seeking more wisdom on the topic.
But it does lead me to this conclusion: arguments made by those without a vested interest in the debate are more credible than those made by people whose income is threatened by the debate. Just as I lack credibility on questions of funding for higher education.
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