Sunday, June 27, 2010

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.


  1. Emily,

    My experience on a primal diet has been similar to yours. Part of my pathway to eating primally was the dissolution of my marriage. Knowing I was falling into a black hole after that, I was determined to throw the kitchen sink at my health so that my wheels didn't come right off. I generally feel calm & relaxed on most days, am generally more motivated, and I have a different level of emotional reactivity. Previously I would have been the type to brood and sulk on an issue. However, increasingly, I deal with most things in the here & now. This might be related to an increased sense of self-confidence since changing my lifestyle too.

    Interestingly, I have gone from being someone on a long fuse (tending toward sulking & depression), to someone who is on a shorter fuse (tending toward being more level but dealing with issues as they come up).

    In terms of my nutrition patients, anxiety states tend to predominate - though I also tend to see a lot of people with gut issues, so perhaps I have a self-selecting population. I only deal currently with one patient who is on prescription meds for depression (fluoxetine) and she has a mixture of depression and anxiety. With her health history I suspected issues with folate metabolism and sure enough we picked up a MTHFR polymorphism in her. She is slowly adapting over to primal eating and has noticed improvements to the point where she is working with her GP to come off the fluoxetine.

    There is an expectation amongst many though, that changes in diet that might deal with depression will lead to them boucing off the walls as in being in a mild state of mania. I think your description is perfect - serenity.

  2. Since you asked...

    I've been eating low-carb for the last 10 months (30 g/day for first four months, then 50-70 g/day).

    Didn't notice any effect on my mood whatsoever. (Generally good mood, not depressed).

    A study published about a year ago did upset the low-carb community (forgive me if you already mentioned it above). The major media headline was "Low-Carb Diets Cause Depression."

    Brinkworth et al put overweight folks on either low-fat or low-carb diet. Mood improved over course of one year in the low-fat, but not low-carb group.

    If memory serves me well, there were more depressed people at baseline in the low-carb group.


  3. Hi Jamie - thanks for sharing your experience. I've had nothing but positive results from my primal diet, and it has been easy to follow. I'm not extremely strict except at home. If I'm out at a party, I will have a cupcake, for example. I try to avoid too much milk protein, as it upsets my stomach. I promise I'll get to GI illness and anxiety soon!

    Hi Steve - thanks for the VLC feedback. I did worry after reading the news reports on Brinkworth's study last year if very low carb might cause depression. I haven't had a chance to look at his study in depth, but will do so sometime over the next week. Depakote, an anticonvulsant and mood stablizer, creates ketone bodies in the CNS. (ketogenic diets are a known treatment for epilepsy, and might not be a half bad idea for bipolar disorder, though I'm not aware of any studies.) Depakote is known to stabilize mood a bit on the low side. (Depakote also causes weight gain and PCOS - interesting that it causes the opposite effects as a ketogenic diet in the periphery!)

  4. I did not know I was depressed until I stopped eating gluten 7 yrs ago. When I gave up gluten I was amazed how wonderful I felt. My brain was clearer, no more depressive thoughts or dark moods. I was amazed in the change. I had not known of my depression as that is the way I always felt.

    About 2 years ago I discovered problems with blood sugar and went on a gluten free low carb no grain diet. I have not noticed any deterioration in mood. Depression did not return. The only time depression returns is if I get accidental gluten. The smallest amount will make me feel depressed, anxious and agitated. This reaction occurs about 12 hours after exposure and lasts a couple of days.

  5. Full copy of the Brinkworth paper here:

    Will try to have a read in the coming days.

  6. Anne - I honestly think everyone should do a gluten-free diet trial along the way. Some people will be able to tolerate wheat, but many will find some surprising results!

    Thanks Jamie - I thought the Archives were for purchase only, and I'm working on getting my institutional access returned after a paperwork snafu left me in the land of free full text this week. Major thing that jumps out on the first read - just as Dr. Parker said - " Of the volunteers who began the intervention, 19 (LC group, 13 of 55 [24%]; LF group, 6 of 52 [12%]; P = .10) were taking antidepressant medication. Throughout the intervention, 1 participant in the LC group took more antidepressant medication, and 2 participants took less. The results of the analysis did not change when the participants who were taking antidepressant medication were excluded." Really? No change in the analysis excluding 12% of the study? And those who had such significant mood issues that they sought treatment with medication?

  7. I took the paper out into the weak winter sunlight for a read today and landed back here to say exactly what you said Emily!

    We are expected to take the authors word for the above as no raw data is provided to allow us to see for ourselves.

    It strikes me as odd that a study that sets out to see whether a particular diet composition has an effect on mood starts out with one cohort containing more medicated depressed people than the other. Why did they not either choose a cohort of people on depression meds before randomisation, or exclude anyone with diagnosed & medicated depression at selection? This really undermines their conclusions.

    The other thing that really stood out for me is that they are comparing the effect of low fat vs. low carb. But they add an additional confounding factor by going down to a relatively low energy intake (~1400-1600kcal). I would imagine that the combination of only eating 1500kcal (assuming compliance) and only 20g of carbohydrate per day (1 banana), that I'd get quite depressed too. 20g is very low carb indeed when you compare to the likes of Mark Sisson's Primal Blueprint where he offers 50-100g as the sweetspot for weightloss.

    Now assuming that everyone in the LC group remained compliant (or both groups for that matter), there is a possibility that persistent low carb at that ketogenic level, combined with low calorie, could lead to depression. And that if you are going to go low calorie (why would you?) a higher carb intake may be required or beneficial from a mental health perspective (or undertaking regular carb refeeding).

    I have doubts over compliance given that only 30% of energy was supplied to participants and after a time they only received $40AUD per month toward purchasing the appropriate foods. Is there a possibility that those in the LC group turned their diet into one that was closer to the LF group? Except they are now dosing with both carbs & fat and caught in a bit of a no man's land? Hard to tell.

    Raw weight measurements are also unhelpful in knowing what has occurred with body compositions. I have increased my weight 2kg since going primal - but I am a darn sight leaner now.

    Overall, too many holes in this one to make it a game changer for me. And the protocol used is quite distant from a low carb primal diet in application (at least the Primal Blueprint variety which is arguably the most user-friendly entry point version - I think Kurt Harris says the PB is the diet you give your vegetarian girlfriend to try!).

  8. anne said:

    Case report of a patient (37 y/o female) with hx of dysthymia and anxiety d/o NOS who began low carb/primal-style diet in mid May and lost approx 20 lbs c/o mild nausea and carbohydrate cravings that she associates with "too high" dose of sertraline. Reduced sertraline from 100 to 50 mg resolved nausea & carb cravings within 2 days.

    I wonder if this is due to relatively rapid weight loss, and/or better endogenous serotonin production associated with dietary changes? Any thoughts?

    (heh - btw this patient is ME and I had a couple of carbohydrate-laden beers tonight so this post is probably not as coherent as I'd like!)

    Emily said: SSRIs like sertraline often cause nausea and carbohydrate cravings. Paroxetine seems to cause the most weight gain, from clinical experience. No one is exactly sure why this happens - though it is thought the antihistamine effect has something to do with it. Psychiatrists prescribe a lot of medicines that cause weight gain - and the more antihistamine and anticholinergic effect there is in the drug (olanzapine and clozapine are extremes in this regard, but paroxetine is also pretty anticholinergic/antihistaminergic), the more the drug seems to cause the weight gain. Something about the antihistamines may affect our insulin (or even leptin?) regulatory system, leading to carbohydrate cravings and then the weight gain.

    It should be said that the weight gain response is highly variable. Some people (especially depressed emotional eaters) lose weight. A type one diabetic patient on an SSRI had to lower her insulin - her serum glucose dropped - likely because she was much more relaxed.

    The other thing that comes to mind - since eating "primal style" I am much more aware of tiny alterations in my state of being. I know exactly when my stomach is a touch more upset. I know if I ate something that makes me crave something else. A single glass of wine has a big effect. Maybe you are noticing a side effect that was already happening on the higher dose, but without the non-primal food messing with your system, the side effect becomes clear? Just a thought! Thanks for sharing your experience.

  9. "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??"

    This makes sense to me because I experienced this! The first month I went paleo/low carb, I wasn't eating any starches or grains like I had been before. I'd eat a generous helping of meat (maybe half pound or 3/4 pound of steak/pot roast/hamburger). After around that amount, you couldn't pay me to eat more of it and the thought of eating more was sickening. HOWEVER, the interesting thing, is that then 5 minutes later my stomach would feel empty and growl-y... BUT my appetite for protein/fat had been satiated. In other words, I felt the physical sensation of stomach hunger but felt a strong compulsion not to eat.

    So I think they might be right, because in a month I got to the point where I'd feel full mentally and physically. I thought perhaps it was just my stomach getting used to not having the starches and grains expanding and filling my stomach, but perhaps it was the serotonin.

    I stuck with it because I had confidence in the scientific literature, but there might have been many more who would take the really ravenous feeling I experienced (but a lack of appetite at the same time) as a signal that their body needed carbs after all and would quit the diet.

  10. Fwiw, Stephan seems to have taken down his linoleic acid/thyroid post.


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