Love and Darkness and my Sidearm

I rather liked The Bourne Legacy, though it is certainly formulaic and silly in parts, but Jeremy Renner is amazing. He's not the most ripped or handsome action hero out there (most of them are comically ripped and/or handsome), but there's something about his acting that is very emotionally appealing. I also have a soft spot for parkour stunts and Moby.

The movie raises some philosphical questions about the morality tweaking human chemistry, for what purpose, and how much do we know�which is the main reason I write this blog. I like to look through the evidence for low-risk, common sense prevention and symptom help for mental health conditions. Going down into the labyrinth of medications for mental health can get very complicated and beyond a lot of evidence base too fast for comfort. The vast majority of the people I see for an intake have already started medications. I'd like to be able to reach some people before that point, when it is reasonable to try a better sleep plan, better food, exercise, and stress reduction.

First off a new post at Psychology Today about a study released last week linking consumption of coffee (with or without grassfed butter, I imagine) to lower rates of suicide. Hardly evolutionary, but certainly low risk, unless you have bad insomnia or anxiety.

Still my favorite Moby song with bonus Gwen Stefani: Southside

A powerful tool to change our biochemistry is to eat good, whole, natural, unprocessed food. Those definitions get muddled enough to be frustrating�but I really mean industrial processing, not the processing of fermentation or sprouting or rinsing, etc. Here are two new cookbooks out to give you some more ideas about how to incorporate convenience into a whole foods diet. Both these books were sent to me free of charge by the publishers for review.

First up is Paleo Lunches (and Breakfasts) On the Go by Diana Rodgers, who is a practicing nutritionist and farmer in the process of getting her RD.  She hosted the amazing farm to table dinner at AHS12 that I'm rather sorry to have missed (already had plans�).

Diana's book is (as advertised) filled with plenty of quick and easy options for lunches and breakfasts. I still admit to eating two poached eggs every single morning, though maybe once a month I change it up with some gluten-free pancakes or a smoothie. Today I made some egg muffins (basically an omelet in a muffin tin), based on a recipe from the book and they were delicious, and the kids ate them with very few threats, even though I added green peppers.

As a working mom, Diana has some of the same time constraints I do. I need fuss-free food that will keep, be easily packed for camp or school, and I don't have time to make special, different meals for the kids. Her recipes (so far) are flavorful, easy, but interesting. I have a special talent for taking great ingredients, throwing them together, and making horrible food (particularly in the crock pot), so cookbooks like this one are essential reading in my house. Diana also told me, "I hate baking," and there is a minimum of mixing and baking in this book, fortunately.

Second up is a book sent to me by Primal Blueprint publishing, Primal Cravings, Your Favorite Foods Made Paleo. I got it in the mail at a particularly busy time and didn't have a moment to review it until now.

I must admit, I was predisposed not to like it. The whole idea of whole, real foods to me is to get people used to eating nose to tail food that isn't dressed up or hidden. The road to nirvana and good health is paved with basic, healthy foods, not paleo cheesecakes. But within the book are a whole lot of easy, basic recipes like broccoli salad, baked eggs, pork cabbage cups. There is a dessert section, and a bread recipe, and fortunately these have a minimum of coconut flour which, in my experience, is rather like getting a mouthful of chalk with your food. I still would almost always rather have a real brownie every now and again than some frankenstein version of it, but then I can get away with a bit of gluten as long as it's not too much. (But you just said above that you eat gluten-free pancakes�yes, I do, because I find pancakes when made from rice flour or tapioca flour or almond flour taste pretty much exactly the same as normal pancakes, and the kids love them.) There are a few kids in the neighborhood now with gluten sensitivity, so if I were to have a birthday party at my house, I would probably make up a batch of one of these recipes, or if I were requested to make a batch of cookies for school or something. More often now, the school asks for fruit which is fine by me. So I suppose there is a use for paleo baking, it's just not a common need for me. And there are even some recipes that will make it easy to use up the supply of beef gelatin I got from amazon (a few tablespoons go a long way when it comes to gelatin, so I have a lot of gelatin to use up!) 

I do like Primal Cravings, and it does have a place on the shelf now growing heavy with paleo cookbooks. Just remember my bias is for easy recipes with not too many ingredients because I can't be too fancy or fussy even for a family get-together (my family usually gets a roast or roasted chicken for those sorts of occasions).

In a couple of weeks I will be giving a talk on disordered eating in the modern world at AHS13 in Atlanta. They rented out a much bigger venue this time, so I believe there are still tickets available. Looking forward to seeing my paleo buddies again! I'm working to make my talk both interesting, evidenced-based and practical so we'll see. Be sure to say hi if I'll see you there.

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Minerals, OCD, ADHD, and Questions

None other than the amazing Dallas Hartwig sent me a link to this paper about OCD and serum mineral levels a while back. It's hard to know what to make of the paper. In Bangladesh, 48 folks with OCD (mostly men) and matched controls had serum measures of minerals zinc, copper, magnesium, manganese, iron, and calcium taken. And, low and behold, the serum levels of those anti-anxiety metals zinc and magnesium (along with iron) were significantly lower than controls, and calcium and manganese were significantly higher. Copper levels were not significantly different.

And that's all we have. One small study, just an observation, a single measurement. Just a blood measurement too, not cellular or other tissue.

AWOLNation: THISKIDSNOTALRIGHT

The main thing I take away from this study is that we still know so very little about nutritional status, minerals, and psychopathology. There are any number of fMRI and other expensive studies looking at the brain in OCD trying to peer into the metabolism of the brain in OCD, and we can learn from those sorts of studies, but we do tend to forget that these are full-body disorders mediated in part by the stress response, so there are some other systemic and measurable clues as to what is going on in the body.

Zinc, magnesium, and iron do tend to be low in people with certain psychopathology. In ADHD and autism, for example, there are several studies showing increased zinc excretion and decreased zinc levels in the body in kids. If you search individually for iron and OCD links in pubmed, you tend to find case studies of kids with pica (obsessively eating sponges, clay, or the padding from couches or other non-nutrative substances) who turn out to have iron deficiency (typically from previously undiagnosed celiac disease). When the gluten is stopped and the iron is repleted, the pica goes away. Iron also tends to be on the low side in kids with ADHD who have ferritin tested, though this larger study showed no association between iron status in the general population of children and symptoms of ADHD.

Are these cause or effect? Do certain variations in mineral metabolism leave you more vulnerable to psychopathology, or do the symptoms expose you to greater stress so your mineral status is different compared to healthy controls? Certainly in the particular cases of the pica "OCD," there is a clear arrow of causation from celiac disease to iron deficiency to pica symptoms. But in other cases the stress will cause people to excrete more magnesium and zinc, which if they are not repleted could amp up the stress response in general and be a self-perpetuating cycle. In the modern world where we get many minerals from our grains and don't tend to drink mineral water, if soils are depleted of certain minerals (and perhaps higher in others due to different agricultural practices) and the phytates in grains, legumes, and nuts bind some of the minerals, all the sudden it is a lot harder to replete minerals than if our intake was more like the ancestral picture prior to agriculture. Combine chronic modern stress with mineral deficiency with a certain genetic vulnerability to ADHD symptoms, OCD symptoms, other anxiety symptoms, etc. and you now have a lot more psychopathology popping up.

One side of the mineral story is the decreased zinc, magnesium, and iron. The other side is the increase in serum manganese and calcium. At this point it is a bit hard to know what to make of that. In certain folks with schizophrenia, there is a certain type of antioxidant-assisting enzyme called manganese superoxide dismutase that has lower activity, leading to poorer ability to clear the toxic metabolic byproducts and presumably cell damage and neurotoxicity. In ADHD (once again), high serum manganese is fairly consistently seen in children with the disorder when it is measured. The same is also true of children with cognitive disorders and other learning problems. Manganese is found in high concentrations in soybeans, rice, and black beans (in which case the associated phytates would protect one somewhat from absorption�but our modern tendency to eat a lot of different processed "foods" made from the same few grains might make us more vulnerable to certain deficiencies and excesses).  Manganese seems to interfere with cell energy metabolism, making it hard to make enough ATP to power the cell.

ADHD is associated with issues with dopamine neurotransmission, and manganese can accumulate in the presynaptic dopaminergic neurons via the dopamine transporter. In high enough concentrations, manganese is absolutely neurotoxic and leads to symptoms similar to Parkinson's disease. Brazilian children with ADHD tended to have high serum manganese prior to being treated with ritalin, which blocks the presynaptic dopamine transporter (therefore increasing dopamine in the synapse). After treatment, the serum manganese levels in these children dropped and presumably there was decreased uptake of manganese into those dopamine neurons.

Calcium's link is even trickier to figure out. Certainly on a synaptic level, calcium flux through membranes is a major "on" switch for neurotransmission. If there is too much calcium flux, you get "excitatory neurotoxicity," and this mechanism is related to migraines, seizures, and probably bipolar disorder. Whether or not higher (but still normal) serum levels of calcium (which, like magnesium, is very tightly hormonally regulated because you can get heart arrhythmias and sudden death if the levels are off) is associated with higher excitatory neurotransmission is unknown to me�hypercalcemia is definitely associated with fatigue, cognitive dysfunction, and irritability, but are high-ish but still normal levels, particularly in certain vulnerable people? I've not seen studies or anything about that, but it is plausible.

Once again, more questions than answers. Typical.

More on minerals

Magnesium and the Brain, The Original Chill Pill
Zinc!

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Zoo Humans

A brand new post is up at Psychology Today:

Zoo Humans

Hat tip to John Durant for the idea and to Erwan Le Corre for the name (and also to the originator, of course, published in 1969 of which I was unaware�The Human Zoo by Desmond Morris which I have now ordered from Amazon. John tells me his new book, The Paleo Manifesto has quite a bit more about primates and zoos in the second chapter. I got a preview copy of the book a few days ago but haven't had a chance to look at it yet.*

Lots still going on! Finishing up the draft of the book, working on chapters and articles for other publications, and (eventually) prepping for my presentation at AHS13. There are a number of interesting papers being published nearly all the time, and I will try to squeeze out more moments to write about them.

*Having read it now, John even has a visit to the Cleveland Zoo! I really enjoyed The Paleo Manifesto and will have a review up closer to the publication date. In short, it is a fascinating foray into one man's discovery of what it means to be human in the Industrial Age. From zoos to religious hygiene practices sex cults to monasteries to skulls to sleep to swimming in the ocean on New Year's Day, John brings together culture and biology to explain the quirks of modern human life.

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Infection and Psychosis in Schizophrenia

Last year the daughter of one of my patients called me. "Mom is acting really strange. She's being aggressive, and she thinks my Dad is still alive. I don't think she slept last night. Do you think she needs an increase in her medication?"

Tame Impala: Elephant

My patient was a sweet 70 year old woman with a psychosis-heavy bipolar disorder who could get paranoid from time to time, but was never violent, and had been stable on a low dose of medicine for many years. I told her daughter, "If she didn't fall down and hit her head somehow, I think she has a urinary tract infection (UTI). You should take her in to see her primary care doctor if she'll let you. Otherwise, you might need to take her to the ER."

A few hours later, the daughter called me back, quite amazed. "You were right! Her doctor says she has a bad UTI. How did you diagnose that over the phone?"

I'm sure all my psychiatrist/doctor readers were guessing the outcome right away. UTIs rather famously turn into strange behavior in the elderly, particularly in those with dementia. One time when I was on call in the emergency room, we got a consult for new-onset obsessive compulsive disorder in  77 year old. My fellow resident and I exchanged looks and told the emergency room intern to wait for the results of the urinalysis before we were consulted. 77 year olds don't develop OCD out of the blue without something else medical going on. We were correct�she had a urinary tract infection. The "OCD" resolved with antibiotics. The tricky part for doctors is that these UTIs can occur without any of the usual symptoms we are used to hearing about. No incontinence, fever, or urinary urgency. Or sometimes the patient can't tell us about these symptoms.

So we already know that urinary tract infections can cause pretty weird behavior in vulnerable people. Recently Brian Miller, MD from Georgia Health Sciences University wrote an article in Psychiatric Times about his recent study in the Journal of Clinical Psychiatry: "A Prevalence Study of Urinary Tract Infections in Acute Relapse of Schizophrenia." Not only do I have a subscription to JCP, but my academic access should grant me full access, but on a Sunday morning I was unable to get a copy of the full text because JCP's website is HORRIBLE. In desperation I emailed Dr. Miller, and on Monday morning he very kindly sent me not only a copy of the full text article, but also his letter to the editor in Schizophrenia Research. Thank you!

Schizophrenia is associated with hugely increased mortality, and those afflicted die in increased numbers and earlier from almost every major leading cause of death. Heart disease is most famous (blamed on the increased schizophrenic tendency to smoke and to the effects of the medications), but schizophrenics have an 8-fold increased risk of death by pneumonia. Is it from lack of self-care and not being organized enough to go to the doctor for serious medical symptoms? Maybe. That has been the assumption. But recent studies have shown what is no surprise to followers of Evolutionary Psychiatry. Schizophrenia is not just a brain disease, it is a disease of immune function. Schizophrenics have major abnormalities in levels of inflammatory cytokines, C-reactive protein, and reduced neutrophil activity. Neutrophils are a first-line response to inflammation and are vital to keeping us safe from bacterial infection. 

Despite all these abnormalities, Dr. Miller notes in his paper that there are NO studies of the prevalence of infection at the time of infection of hospitalization for acute illness relapse in patient with schizophrenia. As all clinical psychiatrists will know, schizophrenics can remain relatively stable for many years, then have terrible relapses of psychotic behavior. Often going off medication or substance abuse is blamed (and may well be responsible). But sometimes something else is going on� and it may well be a bacterial infection. Dr. Miller studied healthy controls and some long-term schizophrenics admitted with acute psychotic relapse. He found that those hospitalized with schizophrenia, men and women, were 29 times as likely as controls to have a urinary tract infection. 35% of subjects in the acute relapse group had serologic/urinalysis evidence of a UTI as opposed to 5% of stable outpatient and 3% of controls. 

There are reports of certain antibiotic treatment associate with increased risk of psychosis (cipro and gatifloaxin are known)� is it the antibiotics, or the UTI they were treating? It is well-known that elderly and particularly demented patients are vulnerable to odd behavior caused by urinary tract infections. It is not beyond the realm of possibility that people with schizophrenia are vulnerable to the same pathology. 

The time is coming that schizophrenia is recognized as a full-body immune dysregulation disorder, from the gut to the brain to the neutrophils. At that point are the psychiatrists going to be removed from the picture and the allergists and rheumatologists to step forward? We'll see. 

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Gut and Brain Again

A long time ago, when I was an intern, I would drive into the hospital for ultra long shifts. Day went into night into the next day. You might be lucky to get one day off in a month. It's illegal now to work interns as much as we were worked, and I understand the sleep science behind the laws. But at the same time, you learn something about yourself and your patients in the long march over a day and a night and a day.

Bono says this song is about a hangover. I used to listen to it on repeat during that sleep-deprived drive into work for those long, long days. In A Little While. I would close my eyes on the elevator in the hospital and hear it playing in my head. Right now I am working a great deal on various projects and of course with my clinical practice. I hope to get a little bit of a break before too long�and have time to do more fun and interesting reading and blogging.

When we are born, we are colonized by the first generation of those eventual 100 trillion bacteria from nearly 1000 differenct species that makes up 90% of the cells of our body. These cells communicate with our brain and likely affect our behavior. The organisms help us to break down complex polysaccharides and they are critical to the normal development of the immune system. A relatively new paper reviews how they might influence anxiety and depression (1).

The mircobiome is influenced by age, diet, stress, metabolism, antibiotics, geography, and genetics. As regards stres reponse, mice lacking a microbiome have an exaggerated hypothalamic-pituitary-adrenal response to stress compared to mice normally colonized. The mircobiome seems to play a role in programming stress response from the very beginning. Stress will also increase intestinal permeability, which gives the bacteria of the microbiome greater access to communicate via inflammation and the enteric nervous system. Microbes can communicate with the human brain via various neurotransmitters, such as GABA, and there is also evidence that different gut bacteria have different effects on serotonin signalling in the central nervous sysem (at least in mice).

When pathogenic bacteria are introduced into the gut of mice, a robust central nervous system response is evident via the vagus nerve, followed by a systemic inflammatory response. Friendlier bacteria (such as lactobacilli) also elicit a central nervous system response, but not the systemic inflammation. Also in mice, certain neurons of the enteric nervous system change how excitable they are (or how easily they signal) depending upon the species of bacteria in the gut. Now repeated in many studies, the infection of mice with pathogenic bacteria increases anxiety-like behavior and treatment with friendly gut bacteria reverses the change in behavior. In some of these studies, changes in the production of nerve fertilizer (so to speak), brain-derived neurotrophic factor, matched the increases and decreases in anxiety-like behavior. The friendly bacteria are associated with greater nerve plasticity and repair, whereas the pathogenic bacteria showed the opposite.

In humans, there are few studies, and none in people diagnosed with clinical anxiety or depression. However, in a double-blind placebo controlled trial of probiotics given for 30 days (2), healthy volunteers who took the probiotic showed significantly less psychological distress than those who didn't. Another three week study showed the healthy volunteers with the most depression-like symptoms had significant improvement on a probiotic while those who took placebo had no benefit (3). There are also positive studies showing probiotics impacting anxiety symptoms in people with Chronic Fatigue Syndrome and undergoing cancer treatment.

Many questions remain that must be further studied. There are differences in how easily the gut microbiome is changed in different life periods, with childhood perhaps showing more amenability to change. In adults it is likely that fecal transplants and the introduction of chronic parasitic infection are the only practical way to permanently affect the microbiome. Childhood exopsure to antibiotics and probiotics may have different consequences than adult exposure to the same.


(2) Messaoudi, M. et al. (2011) Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes 2, 256�261

(3) Benton, D. et al. (2007) Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur. J. Clin. Nutr. 61, 355�361

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APA Annual Meeting 2013

Many months ago, psychiatrist extraordinairre Drew Ramsey, MD of Columbia University asked if I would be part of a group to present information in a workshop format at the American Psychiatric Association annual meeting in San Francisco. He submitted an abstract, rounded up a reputable mentor on the scientific advisory board and collected not only myself but also Mala Nimalasuriya, MS and Roger McIntyre, MD to present.

Leagues: Spotlight

I must admit I've been a very bad academic up until this point. I keep the tip of my little finger in the academic world by teaching the clinical section of the introduction to psychiatry course at Harvard Medical School and have given a few Grand Rounds and other CME talks around town, but I haven't published or done any research besides serving as a psychiatrist for a project in the first couple years after residency. So for me, the opportunity to present at the largest annual meeting of psychiatrists in the world seemed, well, amazing. I do try for the blog to be honest and based on common sense and evidence and practicality, but at the end of the day, it is just a blog, and there are probably 10,000 new blogs on the Internet every single day.

Writing articles for the blog entertains me, helps me to learn, and is a lot more fun than toning it down for the interminable language of scientific papers, which tend to be interesting yet hideous unless written by the best (such as Gabbard or Rook). I do admire those who do publish, like Dr. McIntyre, whose resume is about 80 times as long as mine.

But I never look a gift horse in the mouth, and if they wanted me to present at the APA, I would help deliver�

Drew began the presentation with a brief overview of some important brain nutrients and the concept of whole foods versus the ubiquitous bastardization of wholesome living food we call "processed food." Drew's example: "I went to the store to buy some ham, and it was advertised as 'gluten-free.' When did gluten get into my ham?" He also reviewed some of the dietary pattern studies and elimination diet studies I've mentioned on my blog from time to time. Drew is both an expert at the various nutrients in whole foods, but also anti-"nutritionism," highlighting the importance of combinations of nutrients and their availability in whole foods that is quite different from the stripped down nutrients replenished with salt, industrial fats, and synthetic vitamins so prevalent in processed foods. Drew is the author of The Happiness Diet and the upcoming 50 Shades of Kale (he did indeed order the kale salad at the Split Bread in San Francisco).  I'm going to review The Happiness Diet soon, once I get a minute�

Maya continued the talk with information from her master's thesis on nutrition, the brain, and brain derived neurotrophic factor (BDNF). BDNF is brain fertilizer that helps with neurogenesis and repair, and good nutrition is associated with goodly amounts of BDNF.

Roger followed up with his vast body of work on obesity and mood disorders, noting the effects of weight loss, obesity, and active mood disorders on particular inflammatory cytokines. He highlights the point that the success I see with some of my folks on a paleo-style diet may be a result from an anti-inflammatory state that comes along with weight loss rather than from any particular diet per se.

I was the closer for the presentation with a very brief overview of the evolutionary medicine hypothesis, its pluses and pitfalls, the commonalities of a paleo-style diet and some evidence (including the evidence on fructose malabsoprtion) linking modern diets to poor mental health. I gave a few case studies and my clinical pearls for helping introduce a whole foods diet to people as part of a holistic model for health care in addition to more traditional therapies. I also discussed the theoretical applications of ketogenic diets in psychiatric disorders, the available evidence (almost nil: all pilot trials or case studies), and advised folks to keep an eye out for more research.

We had a number of questions and interest in the ideas of celiac disease masking as major mental illness, coconut and MCT oil, tofu and the poor performance of so called "modern diets" in the dietary pattern studies and depression, and interesting tracks for research and some practical questions about implementing recommendations. At the end we were approached by a number of psychiatrists wanting more information.

Did I mention our room was completely packed with people sitting in the front and aisles and lined up out the door?

All in all, a great success.

The remainder of the APA was, as always, interesting. 15,000 psychiatrists and the launch of the DSMV meant a continuous Scientology protest outside, plus a number of men with bushy eyebrows and bow ties. I attended a number of lectures, the most notable being a 4 hour seminar on giving better lectures. The APA attracts psychiatrists from all over the world, and I would estimate the number of international attendees at 1/5-1/4 in the lectures I attended.

I happen to be friends with the son of a former president of the APA, and as such was able to finagle my way into the APA Presidential Reception at the Palace hotel, which was great fun. My friend's father and his wife very kindly introduced me to everyone, and I can't express my appreciation enough.

It was also great to hang out with Drew Ramsey; food-minded and sensible psychiatrists are always a pleasure to talk to, crossing fingers we'll be invited to the next APA, and I'm going to get his 50 Shades of Kale to help me cope with the mountains of kale I get from my CSA, which starts up next week.

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A Bit of Hiatus

Hi there. Yes, it has been a while. I am spending several hours each day working on the book, so other writing has taken a back seat for the moment. In addition, I am preparing for the upcoming American Psychiatric Association Annual Meeting in San Francisco, where I will be presenting as part of a group on food and the brain (on Sunday afternoon, before the Clinton speech, for anyone who will be there). My next talk after that will be in Arlington, VA, as I have graciously been asked to be a (far less glamorous and much shorter) speaking substitute for the Melissa half of Whole9Life for the summer of Melissa's maternity leave. You can get tickets for the talk here. I'll be adding a bit on the psychology of change and sleep cycles to the general Whole9 information.

Sometime in the next week or so I will have a new (or new-ish) post on Psychology Today. And you never know what will happen if a white-hot paper comes to my attention.

In the meantime, have a lovely spring. Keep checking back, and as always I'm still far too talkative on twitter.

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