Monday, December 31, 2012

Cola, Depression, and Addiction

Over the weekend a little case study popped up on pubmed. Free full text paper, voila:

A case study of cola dependency in a woman with recurrent depression

It's not the world's greatest paper. It's a simple case study, just an introduction that proves nothing. The most fascinating thing about the paper is what we don't know about the consumption of cola, addiction, and mood.

So let's jump in. There is a 40 year old woman who has been on antidepressants for many years, and in addition drinks up to 3 liters of soda every day. She craves soda of a particular brand and has been unable to cut down her consumption in spite of the fact that it is probably interfering with her sleep, and she's developed metabolic syndrome. She feels the soda gives her an energy and mood boost. In fact she meets official criteria for dependence (which are official and written out and require physical dependence and withdrawal syndrome among some other symptoms, but what it all boils down to is continued use despite harm). After a serious exacerbation of her depression, she is referred to an outpatient clinic for treatment.

They work on slowly reducing her soda consumption. Low and behold, she sleeps better, feels better, has better energy, and her depression gets better. She still drinks a bit of soda, but not the massive amounts. She loses weight and stops having metabolic syndrome. She was able to wean off her antidepressant medication and felt good. Success.

So the interesting thing about the paper is what they weren't able to find. There is absolutely nothing in the literature about cola dependence. Nada. Earnest pubmed search comes up empty. And I have several patients with medical issues due to excess calories and sleep problems who overconsume cola to an enormous degree. I myself once drank diet coke daily, and if I skipped a day, would have intense cravings for it, and upon imbibing it I would feel instantly better.

The only "science" the researchers could find was a poll from a Danish radio station, where 16% of 1006 participants considered themselves to be addicted to cola (there is a link in the paper to a website, but it is in Danish). The paper really only considers a sugar/caffeine combo as addictive as part of a reason it might be related to a resistant depression. Of course, caffeine in the form of coffee has actually been associated multiple times with less depression. There is a bunch of literature on that. I have some other theories:

1) Soda in the context of the very common issue of fructose malabsorption could potentially cause inflammation and depression. See: Could Sugar and Soda Be Causing Your Depression?

2) Soda as a source of many empty calories will more than likely compromise micronutrition. See: Soda Begets Zombies

I mean, it is an interesting question. No one is homeless or in jail because he or she squandered all his or her life savings and relationships for the pursuit of soda. But it doesn't take that much imagination to see some very bad long term medical consequences… and the psychiatric consequences desperately need further study. Frankly it boggles the mind that soda is so novel and ubiquitous yet we know so little about how it affects the brain.

Happy New Year!

Tuesday, December 25, 2012

Merry Christmas and Harry Truman

Merry Christmas to all who celebrate! We awoke to full stockings and a bit of snow on the ground.

Yesterday, my sister-in-law gave me a sheet she copied while reading David McCullough's biography of Harry Truman.

Truman was the thirty-third president of the United States. In his seventh year in office, when he was 67, he was described as a "picture of health." He walked two miles almost every morning, followed by an ounce of bourbon. In his diary he wrote the following about his diet in the early 1950s:

I eat no bread but one piece of toast at breakfast, no butter, no sugar, no sweets. Usually have fruit, one egg, a strip of bacon and half a glass of skimmed milk; liver and bacon or sweetbreads or ham or fish and spinach and another nonfattening vegetable for lunch with fruit for dessert. For dinner I have a fruit cup, steak, a couple of nonfattening vegetables and an ice, orange, pinapple, or raspberry…So--I maintain my waist line and can wear suits bought in 1935.

Not sure what a "nonfattening" vegetable is…Truman eventually died in 1972 at the age of 88.

Saturday, December 22, 2012

The New "Perfect Health Diet" and "Sex At Dawn"

One of the perks of being a Psychology Today blogger (besides a small quarterly paycheck) is that I get a ton of newly released books sent my way. Unfortunately, as my daughters are getting older and our lives more complicated, schedule-wise, I have less time to read and less time to post. In the fall, when I teach, my time goes to zero. Unless I forgo sleep (not a feasible option for very long, as I'm not young anymore!), I will be behind on book reviews for quite some time. I feel especially guilty about Toni Bernhard's How To Be Sick and Dr. Drew Ramsey's The Happiness Diet. Eventually I will get to you!

The very first freebie book I was sent came from Dr. Chris Ryan and Caclita Jetha, Sex At Dawn. As I had read Geoffrey Miller's The Mating Mind (which I loved) and Matt Ridley's The Red Queen (also very interesting), Sex At Dawn was an interesting counterpoint to round out the trilogy. Evolutionary Psychology's sexual selection meme is the sobering characterization of women as prostitutes of a kind, trading sexual access for wealth for her children by a powerful male, whereas men are ravening beasts, driven by sexual needs to spread semen every which way. It's not a particularly kind way to look at the human race, your mother, or your father… but science doesn't judge. Enter Sex At Dawn, with the idea that humans are more like bonobos than hierarchical chimpanzees.

The basic message of Sex At Dawn is this one: Humans lived in small, highly related tribes. Sex and marriage were malleable and polyamory was common. Within the tribe, relations were so close that it wouldn't matter much if your woman's child were yours or someone else's in the tribe. "Cheating" is normal and doesn't reflect lack of moral fibre or willpower. It's human nature.

In many ways I like Sex At Dawn, though I do tend to agree with criticisms that it misuses the science to promote one couple's view of polyamory. Having witnessed jealousy amongst my small children from day one, it is hard for me to imagine that sexual jealousy is not a natural human trait (which Ryan and Jetha argue). But from a clinical psychiatry perspective, when I deal with patients who are dealing with infidelity, I do like having the wildly dissident views from Sex At Dawn to discuss with patients. Like 50 Shades of Gray (disastrous from a literary perspective and weirdly conventional, it is widely read so a useful tool to discuss sexual power, the difference between men and women's sexuality, and the power of fantasy), Sex At Dawn sets out a different sexual milepost. A new way to think about human sexuality. My favorite part of it is the determination to cast humans as loving, sensual, social creatures rather than the jealous hoarders we often play. Whether S@D's characterization is accurate is a lesson in critical thinking. I think it is important to read the critiques along with the book.

Which brings me to the new Perfect Health Diet, sent to me not so long ago by Paul and Shou-Ching Jaminet. Disclaimer, they are adorable (as a loving and devoted couple) and amazing and guided me around the Asian grocery store in addition to giving me a copy of both editions of their book. I can't say enough positive about Paul and Shou-Ching in person. Now there is basically no sex in Perfect Health Diet, but it has some similarities to Sex At Dawn. Mostly that it is an earnest, aggressive take on the mainstream, with Paul and Shou-Ching's patented mild smarty-pants writing style. Sodium? Eat more of it. Saturated fat? Healthy! Omega 6 and legumes? Poison in excess! (One of my favorite chapters is the one on Omega 6 fatty acids. The science of eicosanoids is hideously complex, but Paul and Shou-Ching have done their best to discuss the complexity and break it down.

I think that anyone following the food recommendations of the Perfect Health Diet would find themselves in a healthier and happier state of being.  They are straight-up paleo + rice and a bit of dairy with a good amount of carbohydrate, but are moderately low carb and high healthy fat.  I don't always agree with Paul and Shou-Ching with regards to chronic infections, as I feel we have co-evolved with parasites, and our immune systems function best with certain chronic infections on board. I don't know about the safety of their aggressive message for eliminating chronic infections, which our immune system may have sequestered and dealt wih on its own terms. Certainly we did not co-evolve with our modern epidemic viruses and herpes and all that…but it is a complicated area that deserves close study. Anti-fungals and anti-virals tend to be uniquely toxic to the liver and human health.

The reasoning behind the PHD has been enhanced and modified for the new version. They have a breezy, intellectual style, but I think (a bit like Sex At Dawn) they can be a bit guilty of misrepresenting the literature. For example, they credit me (thank you!) for a study I blogged about way back when…Wheat, Rice, and Children's Brains.  We all know it was a crap study in a crap journal (sorry, PLoSOne) and we came up with some damning unaccounted for confounders in the comments. But in Perfect Health Diet, they postulate that the difference between wheat and rice as a staple could account for the differences in IQ between Asian and other children. The literature on sodium is also not as damning as they represent, with some very thoughtful critiques of the key studies easily found in major medical journals.

That said, I like their reasoning about mammalian diets, fasting, and breastmilk as models for human diets. Why not? It gives us something to wrap our heads around. I like the no holds barred questioning of the status quo. One must just keep in mind that no guru has all the answers. No one does.

From a public health perspective, my main message owuld be to eschew processed foods, don't worry about labels and calculations, and to focus on foods which bear no label. I suppose some grains like oatmeal are fine for most, in the context of nutrient rich diets. I'm not the biggest fan of wheat, though some may tolerate it. I love the nutrients in dairy though I don't tolerate it well myself. Corn has some cross reactivity and is certainly guilty by association in processed food.  Rice…I like Chris Kresser's take. I prefer potatoes, squash, pumpkin, tapioca, banana, etc. for starches.

So for people wanting to tweak, and for those wanting to look at a therapeutic ketogenic diet, I do prefer the Jaminets' flexible take. I don't agree with killing all infections at all costs. Not sure the Jaminets do either, though they are far more aggressive than I am.

The new version of the Perfect Health Diet has far more explanation, up to date literature cites, and a more reasonable take on the science behind the macronutrient recommendations. I still think Paul and Shou-Ching are thoughtful like few in the paleosphere. Am I as certain as they are? No, and that gives me pause. But read their book. Like Sex At Dawn, it will open your mind.

Saturday, December 15, 2012

Alternative Therapies and Bipolar Disorder

I will get back to OCD. In the mean time a new paper came out called Nutrient-Based Therapies for Bipolar Disorder, A Systemic Review. And this paper is not written by some press agent working out of the basement of a supplement company. It's the Massachusetts General Hospital bipolar research clinic. I've been in meetings with some of these folks and heard them speak.

Psychiatry in Boston (and the East Coast) is such a funny mix of psychoanalysts and rigidly conservative psychopharmacologists. Apparently on the West Coast things are a little different, with more acceptance of polypharmacy and supplements. But from the center of the most conservative bastion of psychiatry from the 1930s-60s and some of the busiest depression and bipolar pharmaceutical clinical researchers on the planet comes some really cool work with supplements and alternative treatments. I'm a big fan of Neirenberg and Fava over at MGH and their work with alternative therapies. They have open minds and scientific eyes.

Tame Impala: Feels Like We Only Go Backwards

Let's get to it. Bipolar disorder can be difficult to diagnose and more difficult to treat. I try not to judge too much when someone comes to my office with a "bipolar II" diagnosis on the newest, most expensive antipsychotic and a mood stabilizer when they really have depression plus ADHD and/or anxiety symptoms and/or a history of being traumatized. All the diagnoses in the DSM are from the symptom level up, not from the brain pathology down, so things are messy. But despite all that there are plenty of honest-to-goodness bipolar folk who benefit from mood stabilizers… but 54-68% of appropriately treated folks continue to experience subthreshold symptoms, and side effects continue to be a major problem.

Omega 3 fatty acid supplementation may be useful not only for brain health but for physical health. (Of course I personally prefer limiting the omega 6 consumption and eating a nominal amount of cold water oily fish weekly…[practical aside here] one trick is to make tuna salad with 2 cans of light tuna, one can of sardines, celery, pickles, carrot, onion, spices, and your own olive oil mayonnaise (I use the olive oil recipe from Well Fed which is still my favorite "paleo" cookbook, though Eat Like A Dinosaur is great for kid-friendly meals and Primal Blueprint Quick and Easy Meals is also a staple).

Individuals with bipolar disorder are more likely to be obese, less likely to cook their own meals, and more likely to eat sugary foods. And, according to a recent paper (1) looking at the nutrient intake of people with bipolar disorder, they tend to consume food with lower levels of thiamin, riboflavin, folate, phosphorous, zinc, vitamin B6, and vitamin B12 compared to the population norms.

Omega 3 fatty acids work by increasing membrane fluidity and normalizing signal transduction, reducing inflammation, and activate nuclear receptor effects. In bipolar disorder, the first studies were done by Andy Stoll of high doses (around 10g), and over a period of 4 months, there was significantly less depression and higher levels of global functioning. EPA + DHA has the most data, and the amount used in various studies… vary a great deal. ALA (flax oil) was not found to be useful, nor was DHA alone.  Mania doesn't seem to be affected, only depression and general functioning symptoms, and the effect sizes are not strong enough and the intervention not studied enough to take in lieu of regular pharmacologic treatment for bipolar disorder. However, as an adjunct, the risks may be very low compared to possible benefits.

Inositol has also been studied several times (but all small sample sizes) in bipolar depression. (See my earlier post for the mechanism.) Again, as an adjunct, it seems to have some promise for depression, but we need larger sample sizes.

Choline might be helpful by improving and increasing the efficiency of brain energetics. The brain is hungry for ATP (the energy currency of the cells), and in many neuropsychiatric disorders including bipolar disorder, energetics seem to be impaired, possibly by inflammation and oxidative damage. Choline is the main reason (along with all those delectable B vitamins and general yummyness) that I think advice to toss out the egg yolks is idiocy. All the randomized controlled studies of choline supplementation in bipolar disorder are small, and of complicated patients (for example, rapid cycling bipolar and cocaine dependence). One small open label trial by Stoll did demonstrate some benefit for mood.

Magnesium deficiency, as I've discussed in the past, is quite common in the general population. Signs of deficiency include irritability, fatigue, insomnia, loss of appetite, mental confusion, and a vulnerability to stress. Magnesium also has some effects on neurotransmission that are similar to mood stabilizers lithium, valproate, and lamotrigine. There are some small studies of manic patients doing much better with adjunctive magnesium added (one was oral magnesium oxide, the other injected magnesium in severely manic patients). There is only onse study of magnesium as a monotherapy, and 40 meq daily did reduce mania in rapid cycling patients.

Chromium (I haven't written anything on chromium yet… should get on that) seems to improve insulin sensitivty in the hypothalamus and affects the monoamine neurotransmitter systems. Enhanced hypothalamic function may increase the release of serotonin, norepinephrine, and melatonin. There are a few studies showing efficacy in unipolar depression, but not atypical depression, and in the one study of bipolar disorder, there were lots of drop outs.

Folic acid has been studied only once in bipolar disorder, in conjunction with valproate (which interferes with folate metabolism). It seemed to be helpful, particularly for cognitive symptoms. There are more positive studies in unipolar depression, and there's no reason to think it wouldn't be helfpul in bipolar depression (though there are reasons to think folic acid might be an inferior supplement to l-methylfolate, they have not had head to head studies in depression as far as I know).

Rapid tryptophan depletion will decrease serotonin levels in the brain. It can be achieved fairly readily using a tryptophan-depleted drink (see this post for more details). In Canada, it is actually approved as adjunctive therapy to lithium in acute mania, and another study of manic patients showed it might be helpful, but 23% of patients couldn't tolerate the drink. L-tryptophan itself also looked like a promising antimanic agent in a small study of 24 patients (12 grams daily, looks like, for two weeks). However, after it was banned by the FDA in 1989, further studies have been lacking.

In general, nutritional supplementation to current therapies may work synergistically with the therapies (such as folate and valproate), and for many therapies (excepting perhaps chromium and rapid tryptophan depletion), the side effects and risks seem lower compared to the conventional therapies or combining conventional therapies, which is often done with resistant cases now. More larger studies of some of these combination effects would be great to help us clinicians in the field have a larger tool kit from which to work. In addition, the nutritional therapies haven't been tested with consistent dosing or in consistent populations to really give us a sense of optimal amounts or usage. Their potential coud be fantastic.

Saturday, December 8, 2012

Is OCD an Autoimmune Disease

ZZ Ward Put The Gun Down (right click to open in new window, ad at the beginning, my apologies, but song is rad.)

I haven't done much on OCD for this blog, which is silly. I mean, ask any psychiatrist about "organic" mental health disorders and OCD will top the list. It is highly inherited, and there are forms of it that, like rheumatic heart disease, even start after a bacterial infection. Is OCD an autoimmune disease? A fair question.


OCD by definitionObsessive-compulsive disorder (OCD) is an anxiety disorder characterized by unreasonable thoughts and fears (obsessions) that lead you to do repetitive behaviors (compulsions). With obsessive-compulsive disorder, you may realize that your obsessions aren't reasonable, and you may try to ignore them or stop them. But that only increases your distress and anxiety. Ultimately, you feel driven to perform compulsive acts in an effort to ease your stressful feelings.
Clinical OCD is not the same as just liking all your stuff neat or writing notes in rainbow order with colored pens. OCD is a terrible burden. It means an hour long shower just so everything is done in the right order. Countless hidden routines and intrusive thoughts. Nasty, negative, sexual or homicidal intrisive thoughts that are so far from who you are that you are tortured by them. The disorder tends to start in childhood, so it becomes a part of who the person is.


There are certain cases of OCD that begin with a strep infection. These are thought to be due to PANDAS (pediatric autoimmine neuropsychiatric disorders associated with streptococcus infection.) Many childhood cases of OCD involve tics and other movement disorders as well. David Sedaris has a personal take on the experience. 

PANDAS strike with obsessive-compulsions and tics, also increased urinary incontinence, hyperactivity, and a deterioration in handwriting. The strep autoantibodies seem to be attacking the basal ganglia. Straight-up non PANDAS OCD doesn't seem to have these characreristics. So not every case of OCD is a PANDA. 


Classic therapy for OCD involves behavior therapy and SSRIs. And I have patients with OCD on clean paleo diets who still need SSRIs for symptom remission. A rather famous "paleo" character from Robb Wolf's site, "Squatchy" (or Chris Williams) came forward to me with his history of OCD. He said I could share his story. It was horrible for him. He tried doctors, pharmaceticals, everything, for years. Managing his lifestyle for good sleep and exercise and a paleo diet has helped him tremendously. 
It would make sense from a pathologic standpoint that some cases might have inflammatory dietary components that, if removed, would diminish the symptoms of OCD. This fact will not be true for all cases. In Chris' case, multiple factors were at play.



I started having problems with OCD, and Tourette's in about 1st grade. It would get especially bad during the summer. I was miserable, going to bed as early as possible so I wouldn't have to be awake, not wanting to be alive, etc. I had "good" number and "bad" numbers, and even some "good" and "bad" words, and would have to touch everything a certain number of times, usually while thinking certain thoughts when I did so. At times I even had to have some people around me, like my mom, do things a certain number of times, or say a certain word a specific number of times. To say that all of this was incredibly annoying would be a severe understatement. With the Tourette's I had head tics where I would nod my head forward quickly, vocal tics where I would make a sound that I could feel in the back of my throat, blinking, etc. 
...After some time I ended up transitioning into a paleo diet from my previous "healthy diet". Eventually I also stopped running as much, and started doing more strength and HIIT work. I noticed after a while that my OCD seemed to be a lot less prevalent than it used to. Eventually it got the point where it wasn't even noticeable most of the time. I would go through the day, touching things, closing doors, turning off light switches, and not even have OCD type thoughts. Now I would say it's not a problem or even something I do most of the time. In times of stress or if I'm more worried about something in particular, I notice a few OCD thoughts coming back here and there, but even then it's less than it used to be at baseline

More about the pathology of OCD in the next article.