Autoimmune Disease

The first thing you think of when the word "psychiatry" comes up is probably not autoimmune disease. But I see a lot of it, as autoimmune diseases (all kinds - lupus, MS, hypothyroidism, rheumatoid arthritis, asthma, seasonal allergies etc.) bring with them their tough to treat anxieties and depressions. And of course, as a psychiatrist, I'll also get referrals for people with vague symptom clusters of autoimmune-like illness who have been worked up for all sorts of dire things, and when nothing shows up on lab tests, they are shipped off to me. A few years ago, I actually helped write a book for these kinds of symptoms - Feeling Better: A 6-Week Mind-Body Program to Ease Your Chronic Symptoms, so I might get more of these kinds of referrals than the average psychiatrist. (Full disclosure - please ignore the nutrition chapter from the book, if you happen to pick it up! It's more Body For Life than Primal Blueprint!)

For today's post, I thought I might summarize Staffan Lindeberg's work from Food and Western Disease: Health and nutrition from an evolutionary perspective.

From the beginnings of the immune system, our ancestors have used it to fight off attacks strange-looking proteins. Autoimmune problems occur when our immune systems are somehow triggered to take on our own bodies.

How could this happen? Lindeberg suggests the following - start with an increased amount of potential antigens in the intestine from problematic foods, such as grains, milk, and beans. Cereals and beans also have enzyme inhibitors which keep our intestines from fully breaking them down. Then plant lectins in beans and grains open the tight junctions between the intestinal epithelial cells to allow the partially digested, undesirable molecules to pass through. Gliadin, a wheat protein, also activates zonulin signaling, which makes the intestine even more permeable. (Yummy). Heck, "even the permeability blood-brain barrier has been shown to increase with the consumption of wheat lectin." (page 211).

Speaking of wheat - gluten intolerance is an autoimmune disease. In celiac disease, the consumption of wheat and rye (gluten) causes the intestinal lining to be destroyed. It is genetic, but is generally cured by eliminating grains from the diet. Dermatitis herpetiformis is an autoimmune skin disease that is also caused by exposure to gluten, and there is a form of ataxia (difficulty moving due to problems with muscle coordination) that improves dramatically with the removal of gluten from the diet. Other studies have found people with headaches that went away with a gluten-free diet. I've already reviewed the data in schizophrenia.

In rheumatoid arthritis, many patients have anti-milk or anti-wheat antibodies, or both. Fasting has been shown to be helpful, and so have a Mediterranean-like diet and a gluten-free vegan diet that was low in omega6/omega 3 ratio.

Type I diabetes (caused by autoimmune destruction of certain cells in the pancreas) has a geographical distribution that is strongly related to the consumption of cows milk, both on a global level and regionally. The more milk consumed, the more type 1 diabetes is found in a particular area. Immigrants who move to a milk-consuming area start to get more type I diabetes than their relatives who live back in relatively milk-free areas (such as Japan). Beta casein A1 is probably the most likely milk protein candidate, as Iceland has cows who produce smaller amounts of beta casein A1, and their happy milk-drinking people tend to have less type I diabetes than you would expect. Wheat lectins have also been suspected of causing issues with diabetes - as in one study 19 of 23 children with new onset type I diabetes had anti-wheat gluten protein fragment antibodies. Perhaps the wheat lectins open the gut, then the beta casein A1 gets into the bloodstream and triggers the autoimmune attack.

Multiple sclerosis has nearly an identical geographic distribution to type I diabetes, and many people with MS are found to have immune reactions to milk proteins. Wheat gluten antibodies are also increased among MS patients.

Lindeberg suggests, in summary, that there is plenty of evidence that problematic proteins in our food cause autoimmune reactions. Therefore, a trial of a Paleolithic diet for preventing and treating these illnesses is certainly reasonable. If your autoimmune disease is active, he says, reduce the amount of circulating proteins that are contributing to the problem. Don't eat cereals (including wheat), milk products, or beans. Make sure your gut is digesting properly by not eating protease inhibitors such as those found in cereals, beans, and soy. And keep your tight junctions in your gut happy and tight! Eliminate powerful lectins from grains, soy, legumes, and beans.

Sound familiar?

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Low Cholesterol and Suicide

Low serum cholesterol has been linked in numerous scientific papers to suicide, accidents, and violence (1)(2)(3)(4)(5)(6)(7)... there are a bunch more, but I'm a bit weary of linking! This is why I write a blog, and not a peer-reviewed journal. Anyway, no one knows to this day whether depression, violence, and suicidal risk have a metabolic byproduct of low cholesterol, or whether having low cholesterol will predispose you to suicide out of hand (here's a rather snarky editorial pointing out that fact (8)). Some trials of statins (with the resultant crackerjack drop in cholesterol) will show no effect on suicide (9). A statin skeptic's favorite study, the J-LIT trial, showed deaths by accidents/suicides increased threefold in the group with total cholesterol less than 160 (yes, the p was .09, but that means there is only a 91% chance that finding didn't happen by random happenstance (10)).

Now, why could serum cholesterol have anything to do with the brain and depression? Good question - and the first question to ask in any theory of the brain is do the peripheral levels of something have anything at all to do with the central nervous system amounts of the same thing - so do serum cholesterol levels match up to relative amounts of cholesterol in the brain? They do (11). And cholesterol is important in the brain. Synapses, where brain function goes live, have to have cholesterol to form. Brain signaling is all about membranes, and cell membranes are constructed from fat. Cholesterol and the omega 3 and 6 fatty acids are the most important molecules in the synapse. If your brain fat is significantly different from so-called "normal" fat (which I'll go back to the hunter gatherer paradigm and say an HG's brain is going to have the approximate fat constituents for which we are evolved), the signaling in your brain could be very different too (12). Scientific papers will call this "alterations of membrane fluidity." (13)

So we know that low serum cholesterol is associated with suicide, violence, and accidents. (Another wrench in the works - low serum cholesterol is also associated with low CSF serotonin - which is of course associated with increased violence and suicide! These association studies are enough to make anyone give up and go boar hunting.) But does dietary fat intake have anything to do with depression and suicide? (Remember, serum cholesterol is often a chancy thing to connect to diet, after all.) Well, of 3400 some-odd people in Finland, the omega-3 rich fish consumers (14) had significantly less depression than abstainers, but the finding was more robust among women (no one knows why). In this round-up of 408 suicide attempters and an equal number of controls, there was no difference in saturated fat intake between attempters and controls, but the attempters did report lower fiber and polyunsaturated fat intake.

And, finally, do statins cause depression? I've seen statins cause or exacerbate depression several times in my clinical practice, especially in women. (I've also seen them cause paranoid psychosis a couple of times - twice in women and once a long time ago in a man. The psychosis remitted with withdrawal of the statin). Very striking! But anecdotes aren't clinical trials. This brand new study shows no link, and statins actually seemed to decrease depression in elderly women. This study also shows no link. This study shows that chronic cholesterol depletion via statin use decreases the functioning of the serotonin 1A receptors in humans, by decreasing the ability of the receptor to bind to its friendly neighborhood G proteins and other binding proteins. (The serotonin 1A receptor is more highly associated with anxiety-type symptoms than depression).

Clear as mud! But stepping back to whole health, I never like the idea of "the lower the better, no matter what," which seems to be the prevailing winds of cholesterol treatment right now. Usually, chemicals in the body are important for something, or else they wouldn't be there, and typically, a U-shaped curve emerges, where too little or too much (cholesterol, vitamin D, omega 3s, immunoglobulins, you name it!) is bad for human health. Here's an example of the U-shaped curve from the J-Lit trial (via Hyperlipid), showing increased cardiac death at low and high serum cholesterol levels.

Statins may have their role, but please don't put them in the water. In my opinion, adopt a whole foods, paleo-style diet. Keep yourself in the middle of that U-shaped curve for what our human systems were evolved for. It may help your mood, too, especially if you are a woman who eats fish!

(Follow-up posts:  Low Cholesterol and Suicide 2 and Your Brain Needs Cholesterol, Don't Go Too Low)

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Semistarvation Experiments in WWII

This morning I had a chance to read this fascinating article about Ancel Keys' semistarvation experiments of conscientious objectors toward the end of World War II.

For the study, 36 healthy young men who had been excused from armed service for ethical objections to killing agreed to a year long diet of sorts that would include 3 months of preparation, 6 months of semistarvation, designed to make the men lose 25% of their body weight, and then 3 months of refeeding. The purpose of the study was to determine how people would react under such conditions, and then also to learn how to safely and successfully refeed starving populations. The men were highly motivated for the study, and their purpose was to help their country and the young men who were fighting overseas who might face starving conditions themselves.

The young men lived in a dorm at the University of Minnesota, and in addition to their restricted diet, they were required to walk 22 miles a week. All their food was prepared in a dormitory kitchen, and once the starvation began, each man's calories were adjusted every Friday to meet a weight loss goal of 2.5 lbs (1.1 kg) per week. Their average daily calories during the semistarvation period was about 1600 calories a day (they ate approximately 3200 calories daily before the study). I find the number 1600 calories especially compelling, for a standard weight loss diet recommended for a woman is about 1200 calories daily. Their food consisted of what might have been available in war-torn Europe at the time - potatoes, turnips, rutabagas, dark bread, macaroni, small glasses of milk, chicken, toast with a small smear of jam, those kinds of things.

What was it like for them? Well, horrible. They described lethargy, irritability, anxiety that approached each time they were to learn how much they were allowed to eat the following week. They had to institute a buddy system so that none of the men were allowed to leave the dormitory alone, as one man went off diet and had to be excused from the study. They had dizziness, cold intolerance (requesting heavy blankets even in the middle of summer), muscle soreness, hair loss, reduced coordination, edema, and ringing in the ears. Some had to withdraw from their university classes because they did not have the capability to concentrate. Their sex drive disappeared. They became obsessed with food, eating with elaborate rituals (which eating disorder patients also do) and adding water to their plates to make the food last longer. Many collected cookbooks and recipes. One man, tempted by the odor from a bakery, bought a dozen doughnuts and gave them to children in the street just to watch them eat. Originally, the participants were allowed to chew gum, but when many of the men went to chewing about 40 sticks a day, it was decided that gum would affect the experiment and it was disallowed.

Only 32 of the original 36 completed the semistarvation period. One man who broke diet admitted to stealing scrapings from the garbage cans, stealing and eating raw rutabagas, and stopping at shops to eat sundaes. Two of the men suffered severe psychological stress - one became suicidal, and another began self-mutilating, and both had to be taken to a psychiatric hospital (the details or the mutilation and suicidality are not mentioned in the article I cited at the top of the post, but are described in Good Calories, Bad Calories by Gary Taubes. The book Depression-Free, Naturally: 7 Weeks to Eliminating Anxiety, Despair, Fatigue, and Anger from Your Life describes one man cutting off three of his fingers).

The 3 month refeeding period involved trying several different combinations of protein, vitamins, and levels of calories. Dizziness, apathy and lethargy improved first, but persistent hunger, weakness, and loss of sex drive persisted for several months. The men described "a year long cavity" that needed to be filled. The day after they were finally released from the study, one of the men was hospitalized to have his stomach pumped after binging. In the aftermath of the study, "many, like Roscoe Hinkle, put on substantial weight: �Boy did I add weight. Well, that was flab. You don�t have muscle yet. And get[ting] the muscle back again, boy that�s no fun.�" None who were interviewed in their 80s felt there was any lasting medical harm, once they'd recovered.

If you have a moment, the article is definitely worth a read, and it's only 6 pages long. Much easier to digest than Keys' 1385 page textbook based on the research, The Biology of Human Starvation (which I must admit, I have not read, and given the height of the stack of books on my nightstand, I will not be reading any time soon).

Again, what strikes me the most about this study is how close it is to the standard recommendations for weight loss today (500-1000 calorie deficit daily for goal of 1-2 pounds lost a week, plus moderate exercise). The difference is by degree (1700 calorie deficit daily for goal of 2.5 pounds lost a week), and the fact that the men were normal weight when they began the study. But this strict diet sent 6% of the participants to the psychiatric hospital - and these were highly motivated, healthy young men! There is also a marked contrast between the psychological states in this long-term semi-starvation and reports of shorter-term water fasts. And what about bariatric surgery patients - the voluntary surgery leads to forced, sustained semi-starvation, after all. This study shows an improved quality of life and far greater weight loss compared to obese controls, and this study shows improved mental health at 6 months and 12 months post surgery, (though they used a questionnaire called the "SF-36" in which 36 questions somehow covered eight dimensions of "physical functioning, role limitation due to physical health problem, bodily pain, social functioning, general mental health, role limitations due to emotional problems, vitality/energy/fatigue, and general health perceptions.") Finally, this study shows sustained improvement in depression after bariatric surgery with subsequent weight loss, even after 4 years. The differences in the amount of adipose tissue available for fuel may make a real difference (I sincerely doubt this is the case, or else it would be easy to lose weight if one were obese), and most post-bariatric surgery diets it seems to me must be higher in protein than the Ancel Keys diet. Also, there is suspected to be an immediate hormonal change in the body after a gastric bypass, and this may affect satiety and the perception of starvation as the bodyfat set point is suddenly adjusted much lower.

All told, prolonged semi-starvation on turnips and dark bread is not something I would recommend for anyone, if you can avoid it. Perhaps Mrs. Ancel Keys said it best, when she described the effects of the experiment on her husband: "�Mrs. Keys said that Dr. Keys went through terrible times during the experiment as we lost weight and became gaunt and so on. And he would come home and say, �What am I doing to these young men? I had no idea it was going to be this hard.� �

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Anxiety and Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a condition characterized by the chronic experience of abdominal pain, cramping, bloating, gas, constipation, diarrhea, and/or mucous. 1 in 7 people suffer from it, but only half of those have sought treatment. And since there aren't any FDA approved treatments, a lot of people are struggling with irritable guts out there. 61% of people with IBS have anxiety disorders (1), and IBS sufferers report more stressful life events, and their bowel symptoms worsen with stress.

Anxiety itself is the result of an evolutionary adaptation to help us survive during times of extreme duress. Imagine you are hanging out with your buddies by the campfire, and a large animal suddenly joins you, looking for a meal. Your heart begins to race, your breathing picks up, your pupils dilate, blood is shunted from your digestive organs to give you more oxygen in your heart and large muscles, and your senses become acute. Steroids pump out of your adrenal glands to give you increased strength, stamina, and speed, at the cost of fatigue later on. Even your platelets can change shape to become stickier, just in case you are wounded.

Acutely, these changes can help you survive some pretty dire circumstances. But jack up the anxiety response on a chronic basis, and you end up with a classic anxiety disorder - hypervigilance, fatigue, insomnia, panic symptoms, muscle tension, gastrointestinal distress, and worry.

IBS patients have increased startle responses and increased vigilance compared to controls (2), and they have increased cortisol levels at baseline and in response to stress (3). Once again, we have two highly correlated conditions (IBS and Anxiety Disorders) with a similar pathophysiology - for both, possible disregulation of the Hypothalamic-Pituitary-Adrenal axis.

What is the HPA axis? Well, in layman's terms, it comprises three glands in the body that all send messages to each other. These glands control stress response, oversee metabolism, mineral and salt regulation, and basically a whole lot of important stuff, from blood pressure to growth to psychological states. Having that system disregulated is not good. HPA system breakdown is implicated in a dozen disorders, including PTSD, depression, fibromyalgia, and chronic fatigue.

What causes HPA axis dysfunction? Chronic stress, of course, as our body keeps trying to juice us with cortisol to help us battle a perceived threat. But another key cause of HPA axis dysfunction is inflammation. Yup, good old inflammation, the super secret cause of all diseases of civilization. Steroids like cortisol are antiinflammatory, so if our bodies perceive too much inflammation burning out of control, it will send out a wave of cortisol to quench the flames.

Whole books have been written about stress and modern life. Compared to hunter gatherers, we work too hard, play too little, exercise infrequently, hide from the sunlight, and don't sleep enough. And our modern diet, I believe, is highly inflammatory, particularly with regards to linoleic acid (4), fructose (5), and refined flour (5).

But let's step back to the brain, IBS, and anxiety for a moment and check out how they are connected more closely. Corticotropin releasing factor (CRF) is a molecule that works in both the periphery and the central nervous system, and is released in response to stress. CRF, when administered in the brain, causes anxiety and fear behaviors (at least in animals), and when administered in the body, changes the rate of gastric emptying, colonic motility, and increases gut permeability (so all the nasty things we want kept within our GI tract, such as wheat lectin, have an easier time floating through, theoretically, when we are stressed). Rats who are made more sensitive to the effects of CRF have higher rates of anxiety and more sensitivity to colon discomfort (1). For the neuroscience geeks out there - different neurochemicals and neurocharacters implicated in the whole cascade of stress to anxiety and gut issues include BDNF, the NMDA receptor, TrkB and TrkA, 5-HT, monoamine oxidase A, GABA, and the NGF receptor. Most of these activities happen within the amygdala, which is a region of the brain that is highly responsive to sex hormones (which may also explain why women have IBS about twice as often as men.)

Interestingly, sometimes antidepressants help IBS and anxiety. It might help the psychiatric symptoms, the physical symptoms, both, or neither - my definition of a toss-up.

Finally, Peter at Hyperlipid (as always) has an interesting theory about IBS and wheat opiates. Opiates (like heroin, morphine, and percocet) are well known to cause constipation while they are active, and diarrhea and overall discomfort and a lot of anxiety as they come out of your system. It would stand to reason that if someone is sensitive to wheat exorphins, the alternating exposure and withdrawal of wheat through differing meals throughout the day and week might cause alternating constipation and diarrhea, along with abdominal discomfort, the cardinal signs of IBS. Not to mention the anxiety factor. No proof other than anecdotes - but an idea to chew on.

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Genes Are Not Destiny

We are the products of our mother's and father's genes (more Mom than Dad), but a modern understanding of genetics and biology shows us that how our genes are expressed are the product of our environment and what we do. How can that be, when we are allotted a certain genetic hand of cards at conception?

The science of epigenetics explains a lot (and leaves us with a lot of questions too). It turns out that genes can be silenced or turned on depending on how we live, and how we are treated. The body is not just a complicated jelly bag of enzymes and muscle and protein regulation; the very genetic material that directs all the regulation can change shape and redirect what goes on in the first place. So our genes regulate our proteins, but our proteins also regulate our genes.

Following the study of epigenetics, we also end up with the idea that what we do (and breathe and eat) affects our children and grandchildren, too. For example, in a small European community during World War II, babies were born smaller than usual. It makes sense. There was less to eat. But the children who were born smaller then grew up and had smaller babies themselves. Even more bizarre, epigenetic studies show that if your paternal grandfather had plenty to eat between the age of 9-12, your average lifespan is likely to be shorter than someone whose paternal grandfather didn't have enough to eat during that same critical age (1).

Why is this whole concept important to psychiatry? It's all about the brain. The brain has 100 billion neurons. 1.25 terrabyte memory capacity. 100,000 kilometers of connecting neuronal cables (2). Our human brains require many years of careful nuturing and protection as they reach maturity. The wiring process as we grow up depends upon a multitude of factors - nutrition, appropriate social attachment, education. Even after we are fully mature, the brain is still capable of change, or else we could never learn anything new.

Humans are all very closely related. There appears to have been a genetic bottleneck about 2000 generations ago, so that all of us are descended from a small family group that lived 50,000 years ago (3). Two randomly chosen humans have closer genetic similarities than two chimpanzees chosen from the same social group (2). There have been a number of changes over the last 2000 generations, but we are still so much more the same than different. The contention that "all men are created equal" has more scientific truth to it than one might think.

Let's pull all these separate threads together - we are born with a certain genetic hand. We can alter that hand for ourselves, our children and grandchildren by how we live. The brain is the most complicated organ in existence, and the interplay between our genes and how we live will affect the brain in countless ways. Finally, we are all brothers and sisters, and, with few exceptions, have enormous genetic potential for success.

Hardly any of us are doomed by our genes to be obese, diabetic, or depressed. There are simply too many other factors at play to make that flat statement. Yes, if your parents are obese, and you eat and do the same things your parents do, you are more likely to be obese yourself. The logic follows that if we eat and do similar things to what our lean ancestors did, we will be lean. We can't just wait for a new diet pill, a new surgery, a new exercise contraption to solve our problems for us. There are too many factors at play.

With the brain, the factors expand a thousand fold. Lifestyle, nutrition, and proper nurturing are more important for the brain than for any other organ. Hopefully, now, we can finally use medical science to address the whole picture, instead of looking for a single magical chemical or pill. We're all meant to be strong, smart homo sapiens - and we can be, if we work at it. And if genes are our destiny, then we are meant to be that small, intrepid band of humans who conquered the world, for good or ill.

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Depression 3 - Not Quite What It Used to Be

The first written records we have of depression are from Mesopotamia, in 2000 B.C. Those who were depressed were thought to be possessed by spirits, and thus treated by priests. The same was true of mental illness in other records in Babylonia, Egypt, and China, and often a type of exorcism was used as treatment, such as beatings, starvation, and restraint (1). The Greeks and Romans felt "melancholia" had spiritual and physical causes, and thus bathing, gymnastics, special diets, poppy extract, and donkey's milk were used as remedies. Hippocrates himself used bloodletting to help fix an excess of "black bile." Hippocrates described the symptoms of melancholia as persistent sleeplessness, lack of appetite, and depressed mood, along with occasional aggressive behavior, sometimes leading to suicide.

Cicero, a prominent statesman, argued that melancholia was "violent rage, fear, and grief," a similar explanation to Sigmund Freud's (anger turned inward) a few thousand years later. There was even a Persian doctor who recorded use of behavior therapy (rewards for positive actions). Then came the Middle Ages, and we were back to demonic possession again. Some doctors locked the mentally ill away in asylums, but many of the afflicted were thought to be contagious and were burned or drowned. Towards the end of the Renaissance, we were back to baths, humane treatment, and even music therapy.

The Age of Enlightenment brought the idea that mental illness was an inherited weakness of character, so we went back again to shunning and locking people away. However, scientists and doctors were experimenting more and more with different treatments, such as water immersion, a spinning chair, and Benjamin Franklin even came up with an early version of electroshock therapy (2). In the mid 1800s, we begin to get much more detailed descriptions of the symptoms of people admitted to asylums (3). Melancholia was still depressed mood, suicidal thoughts, worse in the morning, with prominent appetite loss and insomnia - very similar to the descriptions of the Greeks and Romans. In the late 1800s, as I remarked upon in my last post, the admissions to asylums skyrocketed. The author of (3) noted that syphilis was often blamed, however, only 14 cases were recorded in the asylum they studied, and that number did not explain the large increase in admissions overall.

Studies of human nutritional history show that rickets (a bone disease caused by severe vitamin D deficiency) became pandemic (especially in urban areas) in the 19th century (4). Here's a description of a common diet in working class England around the end of the 19th century: "The diets of working class women and children too often consisted largely of bread and tea, with sugar and the occasional smear of jam or margarine. Babies of all social classes were generally weaned on �pap��bread and water or bread and milk." (4). Prior to this time, the vast majority of people lived on a farm, with (one would assume) access to fruits, vegetables, fresh meat, and the like. Weston Price found physical and mental deterioration in peoples as they abandoned their traditional diets and began to depend on sugar and refined flour. He also considered appropriate amounts of animal fat critical to good health (5).
I suspect that poor nutrition and deficient vitamin D may have led to quite a bit of mental illness in the 19th century (and today). Deficiency in B vitamins is also well known to cause psychiatric and neurological illness, and much of the cultural worry about physical and mental "racial degradation" disappeared after flour began to be enriched with B vitamins during WWII.

However, even in the early 20th century, the symptoms of depression were consistent with "melancholia." That is, intense sad mood, insomnia, agitation, suicidal thoughts, and appetite suppression. Then, and it is hard to say exactly when (maybe the 50s or 60s?), another type of depression began emerging, called "atypical depression." The symptoms include a milder depressed mood, poor energy, increased sleepiness, and increased appetite and weight gain (via carbohydrate craving). These symptoms are very similar to those of hypothyroidism (though usually thyroid tests are normal) and atypical depression responds to different classes of medication than old-fashioned melancholia. Chromium, a dietary supplement which is thought to suppress carbohydrate craving and speed metabolism, was found to be helpful for atypical depression in one trial. (6). Thyroid hormone (T3) is also used by psychiatrists for adjunctive treatment of depression. Atypical depression sufferers are also much more likely to have anxiety. While I've seen several textbooks quote the prevalence of atypical depression as 40% of depression subtypes overall, I would say in my clinic, the vast majority of my depressed patients have the atypical subtype. I only have two or three patients with classic melancholia. There is argument that atypical depression is actually a subtype of bipolar disorder, but I'm not convinced.

Atypical depression is generally considered milder than melancholia, and may not have shown up in the earlier asylum records for that reason. I've read quite a few novels over the years, and while I recall many literary descriptions of melancholia, I don't recall a whole lot of anxious characters with fluctuating depressed moods gorging on sugar. (That is obviously not a scientific sampling.) But in any event, the United States has done cohort studies every ten years, checking the incidence of mental illness in each successive generation. And in every generation, especially since 1950, depression has increased (increased diagnosis and awareness were, supposedly, statistically accounted for and do not explain the increase). Here's a link to the last cohort study. A woman today who has lived to old age has a 30-40% chance of having major depressive episode sometime in her lifetime. A man's risk is around 20-30% (7). As I stated in the first depression post, major depression and dysthymia (all subtypes included) afflict nearly 10% of us every single year.

Why is depression both changing and increasing? Well, Hibbeln and Salem * note that the dietary omega 6 to omega 3 ratio has also been increasing in the past century (yes, vegetable oils again!) And recall how atypical depression has similar symptoms to hypothyroidism? Whole Health Source has a terrific post linking linoleic acid (the predominant fatty acid in corn oil and other vegetable oils except olive and canola) to suppression of thyroid function at the liver. This would suggest that one could experience metabolic symptoms of hypothyroidism if one had a lot of linoleic acid in the tissues with normal serum thyroid hormone levels. I couldn't find an article noting T3 receptor suppression by linoleic acid in the brain - and this study seems to indicate that it doesn't happen in rat brains (8). Also, in my post on omega 3 fatty acid treatment for major depressive disorder, the depression with anxiety subtypes only trended towards doing better on omega 3s, whereas the treatment of plain depression showed significant positive effects. Since the modern, atypical depression is notable for its prominent anxiety, that may suggest the link to an overconsumption of omega 6 isn't the whole story behind the increase and alteration of depressive symptoms in the past decades.

There are other diet and depression theories also, related to that other "neolithic agent of disease" - sugar (or large amounts of processed carbohydrates in the form of starch.) Rob Faigin, a bodybuilder and lawyer looking for ways to build muscle without using steroids, wrote his book Natural Hormonal Enhancement in 2000. He postulates that a mechanism for modern depression is overall serotonin depletion caused by a diet high in processed carbohydrates (9). Each bolus of carbohydrate would cause a flush of serotonin (and thus good feelings and cravings for more while the carbohydrates are still working in your system), then a fall in serotonin and relative depletion once the sugar rush was over. Thus, in the short term, a switch from a high carbohydrate to low carbohydrate diet might cause depression, but in the long term, staying on a low carbohydrate might free one from mood swings and irritability (10).**

Any of you on low-carb diets? Do you feel depressed compared to how you were on a more traditional diet? While I am not extremely low-carb myself, on a primal style diet (lots of meat and fish, fruits, veggies, and rarely rice and potatoes for carbs, low in omega 6 and no wheat or refined sugars), I am personally more serene, more motivated, and more energetic. These rapid, painless, positive changes piqued my interest in the effects of diet on mood in the first place.

I suspect that depression, like other chronic disease states of Western Civilization, has a multifactorial dietary cause. Linoleic acid to increase the inflammatory soup, and some other factor (sugar rushes and crashes, perhaps?) to fuel the fire. I'll keep looking for more definitive information.

* Hibbeln's paper is extremely interesting, in that he brings up the contradiction between the findings that lower serum cholesterol levels are associated with increased depression and suicide, yet cardiovascular disease (and the higher cholesterol levels associated with that) is highly correlated with depressive disorders (p < 0.0000001!). It's also important to know that Hibbeln quotes a 1985 study by Eaton et al to suggest that saturated fat intake is higher today than it was in hunter-gatherers (9). According to Gary Taubes, Eaton repudiated his previous results in 2000, saying that he had not accounted for the hunter-gatherers eating organ meats and marrow, all high in fat and saturated fat.

**Judith Wurtman at MIT appears to be the major detractor of low carb diets due to possible depressive mood effects, but there is also this quote by her, which doesn't make any sense to me: ""When serotonin is made and becomes active in your brain, its effect on your appetite is to make you feel full before your stomach is stuffed and stretched." The researchers explain that people may still feel hungry after eating a large steak-their stomachs may be full but their brains may not be producing enough serotonin to shut off their appetites." In your experience, are you more likely to eat 5,000 calories worth of steak in one sitting, or 5,000 calories worth of potato chips or candy?? I think the fat/carb combo is far more likely to result in binging than steak. Or butter.

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The Evolution of Psychiatry

In the West a few centuries ago, mental illness was considered the result of personal or spiritual failure. Those who suffered were often considered punished by God, and incarcerated or otherwise treated cruelly (think of Bertha Antoinetta Mason locked away in Thornfield Manor.) In France in the early 1800s, Phillipe Pinel and Jean Etienne Esquirol introduced the idea of the traitement morale, that is, using empathy and compassion as treatments, and they began to develop basic diagnostic categories. A few years later, in Germany, Kahlbaum and Kraepelin, who worked in mental asylums, began documenting and describing psychotic and cycling mood illness. Some of their descriptions are still used as diagnostic criteria in the DSMIV today.

It's important to note that these doctors felt psychiatric illness was biological, that is part of an organic disorder of the brain, much like a stroke or epilepsy. Some of the disorders, such as hebrephrenia (a giddy type of schizophrenia found more often in young people) were extremely common back then, but incredibly rare now. Catatonia (a type of movement disorder associated with schizophrenia - either frozen movement or frenzied, uncontrolled movement) was also much, much more common in Kraepelin and Kahlbaum's catalogs than today.

Towards the end of the 19th century and the beginning of the 20th century, there was a large-scale increase in the number of psychiatric inpatients. Thousands upon thousands of people ended up in psychiatric hospitals. There was speculation at the time that the human race was "degenerating" as a result of some unknown natural selection process. Kraepelin traveled to Java and noted that mental illness was rare there, and felt the "domestication" of the human race was to blame. Unfortunately, he ignored the effects of poverty, poor hygiene, poor nutrition, and lack of education as possible causes of mental illness. His ideas were very influential, and since there was no pharmacological treatment at the time, many countries began measures such as sterilizing anyone with mental illness to stop the decline of the human race. Psychiatric authorities saw themselves as advocates of the mental health of the population (and some advocates of racial purity), rather than as medical doctors who treated individuals. (It is toward the end of this time that Weston Price made his famous journeys, and thus the name of his book, Nutrition and Physical Degeneration, and his preoccupation with the decline of physical, moral, and mental fiber, as it were, in the 1930s.)

We know what happened next. In Germany, the eugenics movement became the systematic extermination of millions of people, all for the sake of a non-existent and meaningless racial purity. Among those murdered were the mentally ill.

One who fled Nazi persecution was Sigmund Freud, and his ideas as to the cause of psychiatric illness were almost entirely different than the psychiatrists of the 18th and 19th centuries. He theorized that mental illness was caused by unconscious and repressed desires, and exacerbated by family situations (particularly problems with mothering) and coping patterns. The treatment, therefore, was therapy (back then, psychoanalysis). A large group of psychiatrists and psychologists were influenced by his ideas, and London and New York became centers of psychoanalytic thinking in the 1950s and 60s. In the next decades, psychotherapy advanced by leaps and bounds, and today there are 10 or 20 different kinds (in my opinion, the best book about the history of psychotherapy is Freud and Beyond). By the 1980s, it became clear that mental illness had both biological and psychological underpinnings. However, even to this day, there remains a false dichotomy - that all psychiatric illness can be cured if one works hard enough and has a good enough therapist, and that psychiatrists don't care about psychology or therapy and only want to stuff you full of pills. Truth be told, social, biological, and psychological underpinnings are all extremely important, and all must be kept in mind when recommending appropriate treatment.

I believe that all psychiatric illness is biologic, meaning rooted in neurotransmitters and membrane potentials, but that genetics, environment, nutrition, and psychotherapy impact how the brain works. The brain is better understood now than ever, which is to say it is still poorly understood in many respects. The vast complexity is nearly unfathomable. In my mind, the study of nutritional and evolutionary paradigms which may predispose us to psychiatric illness have been neglected in favor of psychology and the psychiatric medications. In the next post, I'll focus more on the changes in major depressive disorder over the last century, and speculate as to some nutritional causes.

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