Get Your Sleep On

New post over at Psychology Today about the possible benefits of sleep flushing the brain like a cranberry bog harvest. And some gluten and psychosis and toxoplasma mash-up here in the next couple of days, once I clean the house and get all the candy and mouldering pumpkins put away.

Even Michael Stipe thinks sleep is important in this odd homage to the 7th interval…

Happy Halloween! Don't let the goblins bite.

Heart Rate Variability, Pig Roasts, and Other Randomness

Brand new post is up at Psychology Today:

Depression and a Broken Heart

It is an introduction to the concept of healthy heart rate variability, about which Grayson Wheatley had a featured talk on the first day of AHS13, and he graciously helped me with research for the article. I'm hoping to do a little series on it with some more technical articles here if I have the time.

I just noticed the Psychology Today Evolutionary Psychiatry Blog has been viewed over a million times, which is heartening. Both Your Brain on Ketones and Magnesium: The Original Chill Pill have over 100,000 views. In fact all the older posts have several thousands of views, except A Case of Scratchy Mice, so click on that and give that post some love too.

Sleigh Bells: Bitter Rivals

What has been keeping me busy besides kids, teaching, and paying the bills? Well, I'm working on an academic chapter for an ancestral health textbook, running 5Ks in the dark (fun but very strange, like a fitness rave), and attending pig roasts (another special thanks to Diana Rogers for inviting my family to the amazing Clark Farm, and I can't wait for her next book to come out!). All usually live-tweeted for the psychoanalysts out there.

Electric Run, Gillette Stadium, Boston

The mobile chicken coop at Clark Farm.

The pig. Now in my belly.

Other stuff: The Paleo Manifesto is out, at last. I was able to read a pre-release copy in July and loved it. John Durant makes his journey personal, likable, and pertinent to any modern Western human. He shines new light on the long historical path that we took to get to the here and now, and how we can use those lessons to be healthier, saner, and live a little more naturally wild. It isn't another diet book and is definitely worth a spot on the bookshelf.

Also reading Grain Brain, which is aptly named and seems like it would be just my sort of thing, but so far, I'm not all that happy with it. I will post more if it turns around and by no means is this little blurb to be considered a full review. Dr. Pearlmutter is a neurologist with extensive training and clinical experience in nutrition, but he is militantly anti-carb and suggests everyone keep to less than 60 grams of carbohydrate a day. He states this amount is "one serving of fruit" daily though my nutrition trackers will put a banana at 30 grams and an apple at 34 grams. I'm all for the therapeutic benefit of ketogenic diets and very low carb diets for those who thrive on them, but not everyone will, particularly those who participate in certain types of athletics (like myself) that require a lot of glycolytic work (CrossFit, ahem). I don't think 100 grams of carbs a day, for example, will actively rot your brain in most circumstances. I'm crossing my fingers the book will get better and there has got to be some useful information in there.

The other books I'm looking forward to: Well Fed 2 and Chris Kresser's Personal Paleo Code.

Here come the sheep at a real farm to table experience:

More Zinc Nitty Gritty

On the personal front we are going full speed ahead into fall, school, apple picking, corn mazes, and sweater weather. I also decided to participate in a little n=1 experiment of caffeine elimination for 24 days along with Dallas Hartwig, who apparently does an elimination of this sort at least once a year. He drinks quite a bit of coffee and the occasional detox seems prudent. For me, I figured there wouldn't be much difference in my life with or without caffeine. I rarely drink coffee, and a typical day will see me drinking 0-3 cups of tea, most days one. Since I could skip a day of caffeine without even noticing, I imagined there wouldn't be caffeine withdrawal.

I was surprised about 52 hours after my last dose when the classic headache and a combination of irritability and cognitive fog set in. (Withdrawal can begin as early as 12 hours, typically peaks at 48 hours, and can last 2-9 days total). Mine lasted about 6 hours until I went to bed, and it was gone the next morning. Over the next three weeks, I noticed my sleep was improved, muscle tension was noticeably decreased at the end of a clinic day, and I missed caffeine the most on Monday mornings, Wednesday afternoons (not surprising, my longer clinic day), and, unexpectedly, Sunday mornings. For the first week and even into the second I still didn't feel quite as "sharp," though that feeling began to pass a little by the third week. The experiment ends in a couple of days, and I have plans to moderate my caffeine intake a little more than I did before. Maybe 3 days a week instead of most days a week (thinking of those "most missed" times), and probably won't exceed a single cup of tea. All told, I learned some things, and I'm glad I did the experiment. Probably a worthy one for most people to do, as long as the withdrawal isn't too debilitating.

Last week we left off with some review of zinc, before that a bit of a review of the pathophysiology of depressive disorders in the brain. Today I would like to tie that together from the most recent review article and then discuss the overall human clinical data about zinc as an antidepressant.

Damage to the brain in major depression in the hippocampus seems to occur in part due to overstimulation of the NMDA receptors (by glutamate or similar substances). The overstimulation leads to a large influx of calcium molecules into the cells which results in damage to the neurons and can stimulate programmed cell death. Zinc can turn off this cascade to some extent, because it is a non-competitive inhibitor of the NMDA receptor, which means it keeps the receptor from being quite as easily activated. Thus it could potentially decrease the amount of damage done during a period of high stress.

In addition, zinc spurs the production of the brain fertilizer, BDNF, in the hipocampus, leading to recovery, nerve regeneration, and repair. Below is a modified diagram from the review similar to the ones I posted a couple of weeks ago with much of the zinc penciled in (IN COLOR. hah). For more step by step explanation, please go back to my previous post. Click the diagram to make it larger.

So now, the human data, which works better as a list:

1) In healthy humans, zinc levels in the central nervous system and in the serum tend to be equivalent with free passage through the blood brain barrier.

2) A post-mortum study of schizophrenic patients showed 50% reduction in brain zinc (particularly in the hippocampus) compared to controls.

3) In neurodegenerative diseases, reductions in brain zinc tend to be higher than reductions in serum zinc.

4) Numerous studies link lower serum zinc levels to increased depression scores on a rating scale (there is even some linear correlation, making zinc a reasonable candidate as a biomarker for depression).

5) Zinc levels are lower in treatment resistant patients (in some but not all studies).

6) Patients whose depression improves also have recovery of zinc levels.

7) People who are depressed tend to have lower zinc levels and lower zinc intake (eating less meat, fish, and legumes, and I'm assuming oysters), but hospitalized depressed patients fed the same diet as controls also had lower zinc levels than the controls.

8) Intense, competitive, anxious "Type A" personalities tend to excrete more zinc under stress than the more laid back, "Type B" sort of person.

9) Zinc is excreted in hyperactive kids exposed to artificial food dyes but not in kids who weren't hyperactive in a small study.

10) Zinc supplementation can increase testosterone in zinc-deficient men, and low testosterone is associated with depression.

11) In several (small) randomized trials, zinc (25mg) plus an antidepressant elicited a more robust recovery than antidepressnt alone. Similar results have consistently been found in animal models.

Still, more data is needed, and more information is needed about the genetic differences in people in zinc absorption, sequestration, and secretion in healthy and unhealthy states. The upper limit of recommended zinc intake is 40mg daily, the recommended daily allowance is around 11-12. Temporary supplementation of less than the upper limit during a stressful period seems low-risk, but there is still much to learn.

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.

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!

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

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.