Zinc at Psych Today

Terribly busy between back to school (both kids now have homework!) and my sister getting married last weekend (which required me to be a bridesmaid and also to supply a few adorable flower girls and some quick cross-country flying and jetlag). Also trying to get in our American Psychiatric Association Annual Meeting abstracts on time�my medical school class starts next week panic yet?

I'm still working on the nitty-gritty of zinc and depression from the last paper, but for a review: Zinc! An Antidepressant? at Psychology Today, so each click supports my research, writing, and the blog.

Appropriate new (amazing) song: Hurricane.

Trying to keep active and getting the girls out of doors as much as possible before the winter closes in. Not enough time for writing and thinking, but as always, those are luxuries, particularly in modern times. Doesn't that seem backwards? It seems to me there should be more time for leisure.

Keep eyes peeled for more on zinc and the pathophysiology of depression.

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Pathophysiology of Depression and Happiness

I'll be on the Creative Live video podcast later today (3pm pacific, 6pm eastern) on the topic of happiness (Dave Asprey invited me to participate, and while he is going into some of the technology he uses to monitor his brain and functioning, I'll be talking about some of the research about happiness and different Eastern and Western perspectives.)

Just going through an amazing review from Neuroscience and Biobehavioral Reviews: Potential roles of zinc in the pathophysiology and treatment of major depressive disorder. I'm going to do an updated zinc post (which is why I pulled the paper), but it does have a terrific and concise review of the biology of depression and, as it happens, happiness. Though this biochemistry will not be part of the talk later today. Suffice it to say (click the diagrams to make them bigger if you like):

So diet provides the amino acid tryptophan, but circumstances can push the metabolism in two directions, toward the neuroprotective, neurogenerative and repair pathway (via serotonin and melatonin) or to the neurotoxic pathway. Stress and inflammation tend to favor the production of kynurenine, which can become quinolinic acid (a potent oxidative agent and neurotoxin) or kynurenic acid (which can go both ways, more on that in a bit).

On the neurotoxic pathway, quinolinic acid triggers the release of glutamate via alpha 7 nicotinic acetylcholine receptors and may also directly stimulate the NMDA receptors. High levels are associated with reduced neuronal growth and repair in the hippocampus of the brain along with markers of neuronal injury. Kynurenic acid, also made from kynurenine, can ameliorate this pathway somewhat by modulating the activity of these alpha 7 nicotinic receptors, but in the wrong amounts kynurenic acid can be neurotoxic as well. In layman's terms you get depressed mood, irritability, suicidal thoughts, memory problems, poor resistance to stress, dysregulated energy metabolism, poor sleep or unrestorative sleep. Poor motivation and reduced concentration. The brain just doesn't function well.

On the bright side you get serotonin and melatonin supporting sleep, appropriate circadian rhythms, appetite and hormonal regulation, and then the effects of reduced excitotoxicity via various receptors and components including 5-HT1A, leading to good memory, good neuronal plasticity (which permits adaptation to new experiences and stimuli), and appropriate levels of brain derived neurotrophic factor and dopamine (some of these are mediated by insulin growth factor 1 by the way) toward neurogenesis and neuroprotection. So here we have good memory, good sleep, regulated energy metabolism, positive outlook, motivation, serenity, and appropriate resiliency to stress.

My apologies for the low tech diagrams, but hey, this is a free blog after all�zinc, by the way, plays a role at almost every level in these pathways. But more on that in a bit!

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Does Soda Rot Your Brains Along With Your Teeth?

This study made big news last week, but I was in the midst of AHS13 in Atlanta, and besides the normal conference exhausting insanity, I also had either food poisoning or some sort of gastroenteritis. Only now I'm recovered enough to unbury myself (more or less) from the usual home and work chores.

U2 Some Days Are Better Than Others

I'll do a companion post on AHS13 and my talk there in a bit, but I did want to do a quick review of the horrifying study tracking soda consumption in 5 year-olds. The study was part of a Fragile Families and Child Wellbeing cohort of about 3000 urban US children and their mothers from 20 different cities. The sample is 51% African American, 28% Hispanic, and unmarried mothers outnumber the married ones 3:1. In this cohort,  43% of the 5 year old children consumed at least one soda per day, and 8.2% drank three or more servings a day. Those who did drink 4 or more sodas daily were over twice as likely to destroy things belonging to others, get into fights, and physically attack people, and violence across the cohort linearly correlated with the amount of soda consumed. We've seen a similar pattern in a previous study of adolescents. No one has measured it in young children before.

Covariates included violence in the home, fruit juice and candy consumption, obesity, maternal education, and hours of TV watching, and when the statisticians took these confounders out, the correlations between violence and soda consumption still held. Perhaps the most interesting bit of the study is that fruit juice consumption was correlated with less aggression and candy with mildly increased aggression, so sugar itself is clearly not the whole story here. The authors had all sorts of guesses as to what might be going on, but with the observational nature of the study they are only hypotheses. The main theory is the magical combo of preservatives, caramel coloring, caffeine, and sugar is a quick ticket to aggression and wild swings of blood sugar (though blood sugar wasn't measured). Since soda consumption is also correlated with depression in adults, and depression in parents is correlated to behavioral problems in offspring, high soda-drinking moms might be depressed with high soda-drinking aggressive kids.

Regardless of the whys and wherefores, one doesn't have to go too far out on a limb to say that giving kids soda is a lousy idea, and that the sugar alone is not the problem or only a piece of it (despite my fondness for the fructose malabsorption theory).

Times have changed� (from Gene Simmons Twitter feed) via Mark D. White

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Sunshine and Sad Hamsters

First off, I can't believe this blog is over three years old. Figured that out when I linked an old zinc post, because I completely missed the three year anniversary a few months ago. In any event over the past three years I have seen a greater acceptance of employing grain-free diet interventions along with avoiding processed food, and some more skepticism of the "vegetable oils are heart-healthy" meme.

For example, I missed the December 2011 of Prostaglandins, Leukotrienes, and Essential Fatty Acids (I must admit, not on my regular reading list), but there was an interesting back and forth over a study and a few letters to the editor that were pro modulating the omega3/6 ratio over dumping massive amounts of omega 6 into the diet and making up for that by supplementing with omega 3. The main gist of the editorials was that we don't really know what the heck we are doing when it comes to downstream regulation of omega 6 fatty acids and maybe we should be cautious about eating so much of it. It's nice to see lipid researchers admit that, though letters to the editor are all about some cranky academics espousing their objections to some of the status quo out there.*

Bastille--Pompeii

In addition, the University of Maryland is trying to put together a study to test gluten-free diets in schizophrenia, following on the interesting findings from the CATIE trial that showed folks with schizophrenia were so much more likely to have antibodies to wheat proteins than the general population. Worth a shout out.

But enough about nutrition for now. I really did intend to have more about other evolutionarily appropriate common sense interventions for mental health in this blog, and this week a study came out that fits the bill, at least for hamsters: Nocturnal Light Exposure Impairs Affective Responses in a Wavelength-Dependent Manner.

Flickr Creative Commons

In order to make sense of this study we have to know a little bit about the retina of the eye. Most people are aware that we have light receptor cells in the retina called rods and cones. There is a third set of light receptors in the retina as well called the photosensitive ganglion cells (otherwise known as the intrinsically photosensitive retinal ganglion cells, or ipRGCs), and these cells have the specific job of sending light information back to the suprachiasmatic nucleus in the brain, where circadian rhythms are controlled. The photopigment in these cells, melanopsin, is particularly excited by blue light, of wavelengths around 480 nm. That means that blue light, above other light, is the most likely to send the signal to the brain that it is daytime. Since blue light is nice and bright and makes for nice contrast with cheap LEDs, it is one of the colors of choice for computer screens, tablets, and smartphones. It's also one of the key wavelengths in light from compact fluorescent bulbs that are all the eco-rage nowadays. 

So, as we probably know by now, picking up that phone to send a tweet in the middle of the night is also telling your circadian rhythm part of the brain GOOD MORNING, which the suprachiasmatic nucleus finds confusing, in humans and in hamsters. The ipRGCs not only send signals to the hypothalamus to regulate sleep, appetite, fertility, etc., but also to the limbic areas of the brain, wherein lives anxiety and fear.

In the paper, hamsters were exposed to white, blue or red light (red does not activate the suprachiasmatic nucleus) or left in the dark at nighttime. It is important to know that hamsters are nocturnal, but behavioral changes have been observed in diurnal rodents as well when exposed to white or blue light after dark. The hamsters who were exposed to the white and blue lights seemed more depressed. And by depressed, they actually ate less sugar water than the dark and or red-light hamsters, and there seemed to be reduced neuroplasticity in the hippocampus of the white and blue-exposed hamsters, which is an ominous sign. A fully neuroplastic hippocampus is important to maintaining positive mood and being resilient to stress. Other rodents exposed to nighttime light had reduced performance in learning and memory tasks. Circadian disruption is bad news.

No after dinner iPad for you

But enough about rodents. In August's Current Biology, some scientists took 8 people camping in the Rocky Mountains in July (sign me up!). No computers, smartphones, or flashlights allowed, though campfires were de rigueur. In one week of monitoring the participants in their normal modern environments, they noticed that average melatonin onset occurred 2 hours before sleep start time, which was typically at 12:30am, and melatonin offset occurred after the natural average wake time of 8am. After a week of camping, melatonin onset occurred just after sunset, and bedtime and awake time was moved two hours earlier. While camping the folks also got a lot more bright natural light exposure than in their ordinary lives.

Morning light exposure and early rising are both used as treatments for depression, by the way.

The gist of the study: "Increased exposure to sunlight may help to reduce the physiological, cognitive, and health consequences of circadian disruption.


*describes my blog exactly. Except the "academic" part�

Thanks to Jamie, Victoria, Dallas, and Stephan for emails and or tweets alerting me to the above papers.

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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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