We're Alive! Let's Kiss! Toxo Love Party

You know that scene in a movie when the hero and heroine dive out of the way of gunfire, or outrun an explosion, or in other way avoid imminent demise. They end up in each other's arms, a tender smile, then the kiss. Of course it's all neuroscience and pheromones at that point.

Maurice Jarre, Lawrence of Arabia

Sex and fear live in an area rather deep in the brain called the amygdala. (This name led to no end of snickering among us medical students when Star Wars Episode 1 came out with the character of Padme Amidala. Nerds.)

From Wikimedia Commons

Fire up the amygdala, and you can be more inhibited and fearful. Repress it, and you might find yourself on one of those Girls Gone Wild videos. If you remove the amygdala, animals will get hypersexual, fearless, and hyperoral "in which inappropriate objects are placed in the mouth."(Don't be afraid to follow that link. It's just to the wikipedia article.)

Depressed folks can show increased activity in the amygdala (which could explain the decreased sexual drive and increased paranoia and fearfulness in some depressed individuals). On the opposite spectrum, say you've just survived a fearful situation, and an over activated amygdala is suddenly released? We're alive! Let's get busy, baby.

Okay, what does all this sex and fear have to do with a Toxoplasma love party? An interesting paper came out last month called "Toxoplasma on the brain: understanding host-pathogen interactions in chronic CNS infections." That title might not make you think about sex right off the bat, but the paper is a nice review and has all sorts of titillating information.

Toxoplasma gondii is a little parasite that currently infects more than 1/3 of the world's human population and is often caused by ingestion of cat feces. Alarmingly, the little infectious toxo cysts can persist for a year in the environment and be passed along through contaminated food and water supplies, or through eating infected animals.

Flickr Creative Commons

Once you are infected, the rapidly spreading "tachzoite" stage is followed by a more or less chronic "bradyzoite" stage where slow-growing cysts can form in your brain. These cysts are quite sturdy enough to survive your gut and also protect the parasite from your immune system and from drug treatments. Toxo infections are often discovered incidentally via MRI, or when you have immune compromise (such as HIV infection), or if the cysts grow enough to cause seizures. Chronic inflammation caused by the presence of the infection (or the infection itself) may lead to behavioral and mood problems in humans (see the posts linked below for more details).

Franz Schubert Serenade

Where, then, is the love party? Well, at least in rats, toxo cysts seem to preferentially take up residence in the amygdala. This location will tend to make the rats less fearful and more sexual. In fact, some studies have shown that the infection makes rats more sexually attracted to cats, which sounds like a doomed relationship if I've ever heard one. Cats, eating the infected rats, will pass on the infection to everyone else. Toxo party! It's unclear if the infection similarly causes loosening of inhibitions in humans.  (Pretty sure it's the alcohol that causes those Girls Gone Wild videos, but an observational study checking for incidence of toxo infection in participants might be interesting.)

One final interesting snippet. Toxo (either by the host inflammatory response or by direct release) seems in increase the amount of dopamine in the brain. This finding may also explain why toxo infection is linked with schizophrenia, disinhibition, and paranoia. (Haloperidol, an antipsychotic medication, and valproate, a mood stablizer, have been shown to storngly inhibit the growth of toxo in vitro, but not in vivo.) Testosterone may enhance the growth of toxo, which may be part of why men are more vulnerable to schizophrenia than women. A lot of speculation, really, but very interesting. How much of our behavior is caused or influenced by the little beasts that live within us?

Other toxo-related posts on Evolutionary Psychiatry

Toxo and Suicide in Women
Schizophrenia and Infection
Depression, a Deal With the Devil?

* Roger Ebert is where I first heard the "We're Alive, Let's Kiss" phrase applied to movies.

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Turboboost Your Brain: Eat Meat

That's a bit of a sensational title.  But hey, I guess sensationalism works in the blogosphere these days (or forever in the past and forevermore), and I'm not proud.

Hacienda.  Savage.

Creatine!  We love creatine.  There's lots of it in skeletal muscle, which we omnivores tend to eat and love because steak is oh so yummy.  Vegetarians are low in it and more apt to have mental illness, at least in some observational studies.  Muscleheads have been supplementing with creatine forever for muscle building and power at the gym, but some studies have shown some benefits for vegetarians and folks with Parkinson's disease.  But wow,  a pilot study was published the other day in the Green Journal (the best of the best of psychiatry medical journals) that could blow the door open for more applications for this supplement.  It turns out the medical doctors in Utah are staging a larger follow-up study as we speak, which warrants a mention on Evolutionary Psychiatry for sure.  Thanks to @AnnChildersMD for the link.

Here is the gist of the new study.  A depressed brain has crappy energetics.  It's inflamed and not using energy as efficiently as it could.  That means ATP (body gasoline) is not being created and used as efficiently as possible.  Creatine supplementation, it is well known, can juice up a superfast pathway to create new ATP by increasing the reservoirs of phosphocreatine, which provides phosphate to make more ATP (adenosine-tri-phosphate).  It turns out that depressed brains that respond to treatment with SSRIs or thyroid hormones tend to have higher levels of ATP at the ready.  That finding caused some researchers' brains to click to the "on" position.  After all, only 60% of folks respond to antidepressant treatment (barely better than placebo).  What if we augmented antidepressant treatment with creatine? (For more excrutiating details, follow some of those links in the previous paragraph.)

52 women (in mice, the effect was found to be more profound among female rodents, so female humans were used in the pilot trial to ensure the best results.  I would have recommended female vegetarians, but no one listens to me much) met the criteria for inclusion in the pilot trial.  They had to meet criteria for a depressive disorder, not be on antidepressants,  not be pregnant, otherwise sick, etc.  1/2 the group was put on ecitalopram (lexapro) plus placebo and the other 1/2 was put on ecitalopram plus creatine (3g daily for a weeks, then 5g daily for the next 7 weeks).

Turns out the creatine supplementers responded earlier and better than the antidepressant alone group using a couple different scales (HAM-D and MADRS).  The creatine group had higher response and remittance rate and no higher incidence of side effects.  Sounds like a win win.  Of note, SAM-e may provide a similar benefit, and it is a methyl donor which helps in the natural production of creatine.

So this was a small study, and a single study so more something to scratch your head about and take notice than for any sort of recommendations.  But very interesting.  I'm all for investigating the roots of brain energetics in the pathology of major depressive disorders, and finding inexpensive and practical solutions to make lives with depression better faster.

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Homeopathic Vitamin D Not Effective for Depression

Last week, amidst all the news fall-out over that egg study, Lance Armstrong, and Neil Armstrong, a few other studies were noted that have some EvPsych relevance.

Here is a music selection for the Sunday morning reflective crowd: Chopin's Ballade No. 4

And let's just get it over with:  Vitamin D Supplementation and Depression in the Women's Health Initiative Calcium and Vitamin D Trial.

Okay, HUGE double blind randomized controlled trial.  Over 36,000 women, randomized to placebo or 1000 mg calcium + 400 IU vitamin D3 daily for 3 years.  Depression scores were measured via questionnaire (one I've never heard of, the Bernam scale) and antidepressant use (maybe problematic because different classes of antidepressants have varying uses, for example, TCAs are prescribed for migraines and chronic diarrhea, and SSRIs are used for anxiety) at baseline and several follow up points.  In addition, a subset (828 women) actually had D levels measured during the trial.  Beginning average level was 52 nmol/L which is about 20.8 ng/ml in the units I will typically see on a lab report form.  After two years (and measuring a separate group of 400 some-odd people), the average level in the supplemented group was 28% higher than those who were not supplemented. (Assuming a similar 20.8 ng/ml starting point, two years of D supplementation increased levels to 26.6.)

Kinda scary that the average level of these women at the beginning is just a tick north of absolutely deficient even according to the conservative Institutes of Medicine.  400IU does seem to prevent rickets, and it is similar to the amount of oral vitamin D one might be expected to get from eating cold marine animals.  But it certainly doesn't make up for recommending the entire population avoid the sun at all costs.

In the end, supplementation with 400IU Vitamin D3 (and calcium) was associated with an increased chance of reporting depressive symptoms (the odds ratio was 1.16, though, not too terribly exciting) and not associated antidepressant use compared to placebo.

I'm not surprised, and I'm somewhat annoyed with vitamin D studies and depression at this point.  Studies tend to use teensy levels or enormous ones (and please see that link for a round-up of the relevant D and mental health studies.)  Why don't we find a middle ground between 400IU and 500,000IU (literally)?

I'll share my clinical experience, which, being anecdotal, may not be worth much.  I've been more aggressive about measuring vitamin D in the last few years (as have the internists I work with), and I would say roughly 1/3 of the folks I measure (or have had a D measured in the past year by the primary care doctor) are absolutely deficient.  Meaning below 20 ng/ml.  Levels between 10-15 are common, but I've seen 4s and 8s as well.  The super low folks have tended to have a "sick" look: pale, circles under the eyes, bloated, tired.  (Though not everyone who is pale and tired has a low D by any means!) If I had to guess from just looking at them, I would think they might be fighting a cold or were hypothyroid.  Most of the time, the thyroid function is absolutely normal.

Most of the folks I see have depression, and typically some sort of resistant depression, and I would say 99% of people come to me having already been put on psych meds of some kind.  It's a bit hard to generalize, each patient has his or her own particular circumstances, character strengths, education, and external stressors� but I've figured out that some long-term patients with ultra-low vitamin D finally responded to all the psychiatry mucking around (bolstering supports, lifestyle interventions, therapy, medication adjustment) after the D was corrected.  Shorter term patients have looked better and done better since getting D out of the basement.  I've never attempted an isolated D intervention (which wouldn't be standard of care by any means).

So, while resistant depression generally requires a lot of adjustments in different areas of life to get trending a better direction and to get people more functional and happier, I surmise that replenishing super-deficient vitamin D may be one of those adjustments that ought to be done and likely won't hurt, and seems to be a piece of the puzzle out of place in resistant depression.  Knowing the role of vitamin D in the nervous system so far as inflammation reduction and neuronal repair, there's a sensible mechanism at play as well.

Another interesting bit to the D replenishment story� in the past two years, four of my patients have developed high calcium with adequate D supplementation to bring the levels above 20 ng/ml.  Three of them were found to be hyperparathyroid, and parathyroid tumors were found and later removed, resolving many of the original psychiatric complaints.  The fourth patient is still undergoing a work-up but since a lump was palpated on the parathyroid, it is likely she has a tumor as well.

When I was in medical school, surgeons absolutely loved parathyroid cases because they were relatively rare.  I don't know if four patients in two years is another anecdotal anomaly for me, but I do measure calcium along with vitamin D, and if the calcium pops above 10.2 with supplementation, I'm very quick to refer the patient back to the primary care doctor for further work-up.  Having seen so many cases so recently, I wouldn't recommend supplementing a super-low D (particularly below 20, which is low enough that hyperparathyroidism can be masked by the low D level) aggressively without measuring calcium along with it.  If you have normal levels (say 30 or above) moderate supplemention of 1000-2000 IU daily is probably fine, because if you had hyperparathyroidism, you would already know it, but keep measuring.

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Ancestral Health Symposium 2012 -- The People Post

POP ETC Keep It For Your Own.  Right click to open in new window.

So I had a great (but very tiring) time at AHS12.  In fact I was useless for about 36 hours post-event, with the extra day making it a bit grueling compared to last year, but part of that was entirely my own fault for staying up so late on multiple days.  It was nice to catch up with the personalities and folks and meet all sorts of new ones.  I'm definitely going to miss some folks and for that I apologize in advance.

I was delighted to spend some quality time with:

Mark Sisson:  I was fortunate enough to spend nearly an hour learning a bit more about Mark and his history of athletic endeavors, and how he transformed his experiences and success with primal eating into his Primal Blueprint, and a bit of what his motivations are.  As I mentioned in the last post, most people have an angle.  My disclosure is my paid blog over at Psychology Today, for example.  For the most part, this blog has been a very expensive but fulfilling hobby.  That will change soon when I will make an exciting announcement.  And sure, Mark wants a successful business, but it is also extremely important to him to help folks eat better and live better.  He has always done a good job advocating for balance and common sense.  I've heard him say multiple times� the goal is not to get the body of a Sports Illustrated swimsuit model.  It's to be happy and healthy, and *not* to be obsessed with food.  It's to eat well in such a way that you don't have to spend so much time thinking about it, counting, or carrying around little snacks to eat every three hours.  It's to be able to tolerate a fast every once in a while if you are traveling and there's nothing that good to eat.  It's to eat well most of the time so that you can enjoy champagne and cake at your great aunt's 100 birthday party (barring alcohol problems or wheat allergy) without worry or recrimination.  In any event, Mark is good people and it was a great pleasure to get to know him better.

Stephan Guyenet: I really enjoy talking with Stephan each time I have the opportunity.  He's thoughtful, careful in his writing, and an exceptionally kind person.

Chris Masterjohn and Denise Minger: We were able to talk a bit about Chris' successful defense of his dissertation (on a topic I have a great deal of interest in, certain specific aspects of glutathione metabolism) and Denise's writing project.  They seemed a bit more relaxed than others at the conference, maybe because Chris got that PhD...

Chris Kresser:  Somehow each time I talk with Chris I tend to be fired up about something, so I'm not sure the impression he has of me!  He understands the dilemma of a clinician, that things aren't always so simple, that lab tests aren't always accurate, and that the answer isn't always more supplements or less sugar or whatever the paleo flavor of the week is.  I'm always eager to see his new writings and ideas.  It's also nice to talk shop about babies and parenting.

Rick Henriksen MD, Catfish MD, Primal Mountain (Jacob Egbert, DO), Vlprince, and Dr. Lucy:  I can't say enough about this crew of doctors.  We were pretty much inseperable during the event, and various folks did everything from help me with my sinus infection, share chocolate, phone chargers, buying dinner, introducing me to all sorts of great practitioners, and even bringing me farm fresh rendered lard and putting me up for a couple nights in town so I wouldn't have a 45-90 minute commute each way.  The three day event would have been nearly impossible without their support and company.  I love them all a great deal and can't wait until we all meet again.

My sister in law, an emergency room nurse who volunteered for the event and by the end seemed to become friends with everyone.  (And a special thanks to my husband for wrangling the kids alone as he is always happy to do when I'm away for these shindigs.)


I had a few moments (and would have loved to spend more time) with:

Ned Kock, Beth Mazur, Paul Jaminet, Keith and Michelle Norris, Basil G, Aaron Blaisdell, Jamie Scott and Anastasia Boulais, Grayson Wheatley, Dallas and Melissa Hartwig, Kamal, Don Wilson, Lindsay, Colin Champ, and Squatchy and countless others.

Someone I would love to chat with more, but I figured it would take some time to do it justice and he was always mobbed:  Robb Wolf.  One day, maybe!

Finally, I wanted to address some concerns that have come up on the Internet about our physician's forum.  Some great practitioners (chiropractors, RDs, nurses, etc.) felt left out because our little endeavor is for MDs/DOs, medical students, and the international equivalents.  We think other practitioners are terrific, incredibly valuable, and certainly have skill sets we do not possess, and an eventual plan would be to have several nested forums with all clinicians and researchers or whoever able to share ideas, grant funding, experience, resources, etc.  Our forum is quite small at the moment and is focused on addressing specific concerns and needs of physicians, having to do with medicolegal questions, evidence-based practices, case studies, etc.  For various legal and traditional reasons, this model can only work with a confirmed set of physicians.  We're not trying to be exclusive or leave anyone out because we are jerks.  This model meets our current needs and we hope to collaborate with all kinds of practitioners in the future.

There has also been a lot of discussion about AHS12 and the quality of speakers, the lack of diversity, and the judgmental atmosphere.  I felt the speaker list was more diverse than last year, and interest from many ethnic groups is growing.  These events filled with nutrition fanatics and folks who work out for a living is always a bit of a beauty spectacle.  Many folks get into evolutionary styles of eating and living for reasons of vanity (hey, I did�).  I'm not perfect by any means, being a middle-aged mother of two, but I personally felt comfortable and that people weren't judgmental to my face, though I'm not going to be walking around the AHS in spandex any time soon.  Its unfortunate that others felt judged or uncomfortable or excluded.  I thought the talk by Dr. Eaton about ageing gracefully living a paleo lifestyle was a nice antidote to the youth obsession� but I'm one of those folks who generally assumes others are thinking kind thoughts and giving people the benefit of the doubt, so maybe I'm not the best one to judge these sorts of things�

Jacob Egbert and Rick Henriksen

Don Wilson

Catfish

Victoria Prince and Lindsay Starke

Me, relaxing in New Hampshire a few days after the conference

Well, opinions and criticisms are useful, particularly if they lead to reflection and self-improvement.  Real time evolution, if you will.

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AHS12 as a Practicing Clinical Physician

This past weekend I had the terrific opportunity to attend the Ancestral Health Symposium 2012, and also speak to a much larger audience than I could have anticipated.  I'd been to the original symposium in LA last year, and got a real sense of how much the interest in ancestral health lifestyle has grown in such a short period of time.  I'll probably gossip a little more in a later post, but for now I wanted to give some of my personal ideas inspired by the excellent post of Paleolithic MD, a Physician Manifesto.

Last year, I was thrilled when two physicians came up to me and we were able to talk a bit of ancestral health shop.  Sometimes being a Western physician interested in ancestral health principles can feel incredibly lonely, exhilarating, and even frightening.  In March I went to PaleoFx and met a core group of family medicine and physical rehabilitation physicians from Utah who wanted to organize a physician's forum.  We bonded immediately, because we have such similar experiences and goals that are not exactly shared by anyone who has not tried to juggle the practice of clinical medicine and evolutionary medicine principles.  Doctors have particular needs, obligations, regulations, and a widely varying patient base, ranging from those who are very ready to make healthy diet and lifestyle changes and those who will continue to smoke while dragging around an oxygen bottle.  

Everyone comes to see a psychiatrist from a different place in life.  I might not talk too much about diet for months or years of working with someone because we are working on keeping someone employed, brainstorming about how to keep from being homeless, or working on how to keep from self-injuring, drinking, or suicide.  Sometimes folks embrace dietary and lifestyle changes as a part of a solution to these enormous problems, but sometimes they cannot or will not� and some may come to me years later and begin to ask about nutrition or sleep, but many, many folks never will.  With very few exceptions, I do not kick people out of treatment just because they don't follow my advice.  Nor can I judge when someone with particular temperament, education, family situation, and stress is not prepared to make major lifestyle changes.  I don't live in anyone's shoes but my own.

After PaleoFx, the Utah docs and I began the embryonic stage of a forum for MDs, DOs, and medical students, and at AHS12, put out a call for other physician attendees to come and talk about joining forces for support, education, and other practical considerations.  Rick Henriksen, MD, on faculty at an academic medical center in Salt Lake City, has done a great job putting together statements of basic principles and ideas.  While AHS11 had a great introductory and research focus that was expanded into AHS12 to include even more anthropology, different angles on the science, and some of the old tired arguments about whether glucose will kill you or not.

We were all surprised when 30-40 people, mostly physicians, showed up, interested to network and learn.  Of course one travels to a conference to network and learn, but I hadn't realized there were quite so many physicians in the "fold," as it were, and if there are this many physically attending the conference, how many are now out there in the community or academia?

Doctors for the most part do not want to burn down the academic medical center.  We want to integrate the best sensible practices of Western medicine and ancestral health principles.  While everyone (including me) can bemoan the number of C-sections and the (lifelong?) alterations in microflora that might involve for the infant, I was seated between two very amazing doctors, both born by C-section, who might very well have perished along with their mothers at birth without the intervention.  I've seen midwifes claim rates as low as 2% C-section, and the near 30% rate in the US is no doubt too high, I don't know that anyone who cares for women and babies who would say the C-section rate should be 0%.

The clinical medicine place where allopathic and ancestral health principles meet is in proper nutrition, preparation, and education to help a mother be as healthy as she can be prior to conception and pregnancy and to avoid some of the complications that may increase risk of C-section (such as obesity, gestational diabetes, or hypertension).  But again, some women won't or can't make the changes that could ameliorate these complications, and sometimes the changes simply aren't enough.  Then the key is to be educated and experienced in childbirth to minimize unnecessary intervention, and to know when to act decisively if a vaginal delivery is not possible.

Often antibiotics are overused, but sometimes, if you don't take antibiotics, you will hasten your death or end up with a disfiguring surgical wound infection.

Physicians must navigate the evidence, plausible biologic mechanisms, unknowns, and various corrupting or biasing influences.  There is the industry money from pharmaceutical companies or supplement companies or shoe companies or traditional entrenched methods that may have no basis, personal pride or narcissism that might make the doctor recommending pig thyroid for everyone seem like a convincing plan, but ultimately the harms may outweigh the good.  There is a mountain of information to negotiate and the motivations of the presenters of the information to consider.

And sometimes there are health problems that can't be changed, but only borne.  Supporting someone in coping can be the physician's most valuable skill.  It is perhaps the oldest one.

As far as the practical implications for ancestral health in the western medicine paradigm today and in the future, I'm most excited about the potential for widespread support of a whole foods, anti-inflammatory, processed-foods restricted diet, and the end of academic dietitian and nutritional support of micro nutrient-poor and then enriched processed foods as "health food."  I'm also interested in the possibilities of immune modulators such as helminths and pseudocommensials for autoimmune disease, and learning more about how technology use affects sleep and mental health.  Other things, such as being on the lookout for iron overload and encouraging regular blood donation, particularly for men, and learning how to avoid toxic imbalances of nutritional supplements while using them judiciously to replete deficiencies will continue to be practical yet tricky.

With all the tinkering, in Western medicine and in ancestral health, we don't want to lose sight of the basics.  Now matter how healthy I make today, I can't undo the sleep-deprivation of the past weekend.  No matter how many times I quantify hormone levels with lab tests, I can't get your hypothalamus and testicles or ovaries or adrenals to work together if you don't help them out by eating and sleeping and laughing enough.    

I'm excited about the future collaboration of evolutionary-minded doctors.  Now, getting doctors to agree on much of anything can be like herding cats, and establishing some maverick (but very sound!) principles in the age of increasing pressure for evidenced-based medicine to be cookie cutter medicine delivered from a manual can seem daunting.  As doctors, however, the first thing we must remember is to meet the patient where he is.  If we start there, it is much harder to fail.  Our job is to exemplify, as best we can, good principles of healthy living and to deliver support and healing.  We will do a much better job integrating the best science of modern medicine and the sensible, proven traditions and experiences of our human past.

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Mainstreaming

For all that I have a jabbery twitter account and like putting filters over my crap pictures for posting on instagram, I'm not exactly the kind of person that when you meet me for the first time, I'll say, "HEY, HAVE YOU SEEN MY BLOG??"

In fact, many of my friends and patients don't even know I have a blog.  It's sort of a niche audience.  But as the years go by and the archives build, more and more I will talk to a colleague or therapist who might refer to me, or even someone at the gym, and they will say, "Oh, by the way, I saw your blog�"  

The colleagues are especially exciting.  In the past few months I've been invited to a few more journal clubs and Grand Rounds to speak to more psychiatrists, neurologists, and other head-interested professionals.  Some of these folks might even have a research budget.  I really love these opportunities, because when it comes down to it, Evolutionary Psychiatry is not about the paleo diet.  It's about the pathology of mental illness and conceiving our brains as connected to our bodies and guts and environment.  It's about how physical and mental health are derived from our genes and the protoplasm of the world around us.  It's about simple interventions and the complex ways in which they influence our nerves and hormones and flesh.

It's a niche audience, but I feel Evolutionary Psychiatry deserves to be mainstream medicine.  It's about asking questions in a common sense fashion, and approaching disease with multi-pronged, inflammation-reducing and neurotransmitter-savvy and sensible solutions.  It's about acknowledging the wisdom of the past generations and translating the therapies and traditions into real results.  Mostly it is about asking the questions in a way that will generate the answers we need for the science to be useful.

My daughter asked me if the iPhone knew everything.  I said, a vast amount, no doubt, if you ask the question just the right way.  She will never remember an early life without Siri.

I didn't plan on blogging today, but in my mailbox arrived the brand spanking new fresh edition of the Green Journal, and two of the articles just SING evolutionary psychiatry.  So here I am again.

A Silent Film: Danny Dakota and the Wishing Well (reminds me of those angsty John Hughes movies from the 80s, before he started doing movies about John Travolta and babies)

The first article is a double-blind placebo controlled trial of NAC in cannabis-dependent adolescents (1).  I know there is a bit of a link between paleophiles, libertarians, real food hippies, and weed, but I've never been a big fan.  Mostly because I'm often confronted with parents and older adolescents who struggle with psychosis and/or lack of motivation and crippling anxiety who smoke pot ALL THE TIME.  Not to mention the older folks who come in after decades of daily heavy use and can barely finish a sentence.  I've covered it before here and here.  Weed has some interesting properties, no doubt, but I've seen it to be more the fountain of rotten brain, agoraphobia, and dementia than the fountain of creativity and youth.  My sample is not randomized, and I have no doubt of that.  But roll the dice and take your chances, as they say.

ERGO, I think finding ways to get adolescents to smoke less pot might be a good thing.  And in the linked paper, it is noted that 25% of high school students use pot, 7% on a daily basis.  Besides standard psychosocial therapies, there's not much out there to help adolescents quit the dependency.  Could a pill help?

NAC, as we know, is particularly exciting in psychiatric disorders because it targets glutamate and antioxidants in a novel way.  There's no prescription pharmaceudical with the research data or similar mechanism.  In animal models, self-administering addictive drugs down-regulates the cysteine-glutamate exchanger in the nucleus accumbens.  NAC upregulates this exchanger, reducing the reinforcement of drug-seeking.

The authors of the study did a promising open-label pilot trial and then organized a larger randomized controlled trial.  Cannabid-dependent adolescents (13-21) who desired some help and met other exclusionary criteria were randomized to placebo or 1200mg NAC daily for 8 weeks.  All participants received cessation counseling at every research visit.  Cannabis use was determined by urine sample (which will be positive for about a month with moderate cannabis use, depending on body habitus).

In the NAC group, 40.9% of the cannabis tests were negative (assuming all missed urine tests were positive).  In the placebo group, 27.2% were negative, a statistically signficant difference.   Participants who had made the decision to quit and were negative at baseline were six times more likely to be abstinent through the rest of the study, those with fewer years of use were more likely to be negative, and those with major depressive disorder were more likely to continue using.  There were no significant differences in adverse events between NAC and placebo users (like most studies, NAC users had fewer side effects than placebo, 38 in the NAC group and 46 in the placebo group).

These results should be repeated and consolidated at multi-treatment center groups, but all in all it adds to the NAC family of interesting psychiatric results.

The Ting Tings Hit Me Down Sonny

The second interesting article is about poor nutrition at age 3 and schizotypal personality at age 23.  Studies of populations in China and the Netherlands have shown that periods of famine during pregnancy results in the birth of children who are twice as likely to have schizophrenia or schizoid personality, and the risks can be worse when malnutrition extends to the postnatal period.  Thinness in childhood from malnutrition is associated with later schizophrenia as well.

Is it the malnutrition or some other variable that increases the risk?  Malnutrition is associated with low IQ, and low IQ is also associated with the development of schizophrenia.  Iron deficiency is associated with malnutriton, stunting, and schizophrenia.  Let's try to sort it all out�

In Mauritius, all children (1795) from two towns born in 1969 to 1970 were followed from the age of three.  Height (in developing countries, a measure of nutitional status) and hemoglobin (which is an indirect measure of iron) were collected and normalized for the different ethnic groups.  An "adversity index" was also measured from a home visit for each child, counting points for uneducated parents, semiskilled parents, single parents, separation from parents, large family size, poor health of mother, teenage mother, or overcrowded home.  IQ was measured at age 11.  Schizotypal personality was measured with a questionnaire at age 23.

The researchers found that poor nutrition in early childhood resulted in poor cognitive performance (IQ at age 11) and a higher risk of schizotypal personality at age 23.  The adversity index at age 3 was also significantly related to IQ at age 11.  Individuals with higher performance (vs. verbal) IQs were less likey to have schizotypal features.  It is thought that malnutrition leads to hippocampal and frontal brain impairments, leading to difficulty with emotional regulation, maintaining relationships, and the all important executive function.

How do these finding play in the first world?  I suppose it depends on how many pregnant young women live off of vending machine food.  Still, more evidence that nutrition is important.  As if we didn't know.

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Teenagers, Mood, Psychosis, and Omega 3s

AHS12 is next week!  In New England all the short-sleeved outdoor fun has to be squeezed into about 8 weeks of decent weather, so I'm taking it one day at a time at this point.  But I did manage to put together my presentation (which is on Friday at 4:15) over the weekend.  I swear when I looked at the schedule the first time I was directly opposite Mat LaLonde, but it turns out I'm just after Mat but in another room, so I'll stop grousing (though Maelen Fontes' antinutrients looks really interesting too.)

I don't have a lot of time, so I'll be looking at trans fats and carbohydrates and how they affect mental health.  It should be fun, and even if you follow my blog religiously you won't have seen all the stuff that will be covered.

But back to other interesting papers I've come across recently.  The first one is from the Archives in Feb 2010 (1).  These researchers randomized 81 people at ultra-high risk for psychosis aged 13-25 years to two groups.  The individuals had to have experienced a brief and mild psychotic symptoms already or have high genetic risk (typically a first degree relative with a psychotic disorder) and loss of social functioning.  Young people with these sorts of symptoms have about a 40% chance of developing a full blown psychotic disorder within the next 12 months when followed in previous research. 

Identifying and treating these ultra-high risk individuals is a hot topic in research today, since preventing schizophrenia, if possible, would obviously be a lot better than having someone suffer devastating psychotic episodes, hospitalizations, or having to drop out of college.  Defining the group of individuals to study has led to some misperception about the diagnostic category "psychosis risk syndrome" which to many seems like psychiatrists are trying to pathologize eccentricity among youth.  The category was developed to have consistent criteria for these preventative-style research projects, not to try to change every teen-ager with black-eyeliner and an interest in ESP into a polo-wearing business school student.

These caveats are not to say the research isn't controversial.  Sometimes it involves putting ultra-high risk kids on antipsychotics to see if it will prevent conversion to schizophrenia or other full-blown psychotic disorder later on.  Any time one treats generally healthy young people with drugs with lots of side effects, one had better be trepidatious.  However, the study I'm referring to took a much less aggressive approach.  The 81 young people either took an omega 3 fatty acid (700 mg EPA, 480 mg DHA, and some vitamin E as mixed tocopherols) supplement for 12 weeks or placebo (1.2g coconut oil and the same vitamin E).  Adherence was calculated by measuring RBC (red blood cell) membrane fatty acid content and by self-report.  No use of antipsychotics were permitted (or if full blown psychotic symptoms were present for more than a week, standard treatment was started and the individuals left the study), and both treatment and placebo groups had some standard psychosocial counseling sessions (helping cope with stress, learning life skills, etc.).

After the 12 week treatment period, the groups were followed closely for the next 9 months.  Among the placebo group, 11 of 40 (27.5%) developed full-blown psychosis during the 12 month study.   Only 2 of 41 (4.9%) in the treatment group developed psychosis.   The difference was statistically significant and comparable to similar studies using the far more toxic atypical antipsychotics.  That's an impressive result for a relatively simple intervention and it would be nice to see it repeated at different medical centers.

The next study (2) was published earlier this year and measured RBC membrane fatty acid content in 150 adolescents admitted to the hospital for treatment of depression vs. 161 controls.  Long chain omega 3 fatty acids play all sorts of important roles in the brain in membrane signalling, synapse formation, dendritic growth, and seem to help facilitiate communication and repair.  Low omega 3 levels in the red blood cell membranes correlate with sudden cardiac death and depression in adults, though supplement trials with omega 3 have had mixed results.  There were two major problems with the study--cases and controls were significantly different with respect to ethnic groups which might affect genetic differences in metabolism and conversion of dietary fatty acids to those incorporated into the membrane.  Also, no attempt at dietary measures were taken, so it is unclear whether differences are from metabolism or dietary differences.  

However, in the end, the lower the DHA in the cell membrane, the more likely a subject was to be in the depressed hospitalized group.  More to look into!   

 

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