Thursday, March 19, 2015

Genetics

We've been struck by a harder than usual winter here in the Boston suburbs, and the spring bounceback, where increased light meets slow-clogged sidewalks and freezing temperatures, has been worse than in times past. Insomnia is a major problem along with irritability and reversed sleep wake cycle.

In the coming month a couple of blog posts on sleep hygiene and solutions for more serious insomnia will be published on the 9blog.

I've just now posted a blog about major mental illness and the genetics of seasonality at Psychology Today.

In the mean time, I've been wanting to expound on genetics and psychiatry for quite a bit. In the past few years, companies have been courting the psychiatrist, enticing us to get some genetic information about our patients. The jury is out scientifically as to whether that information is useful in the general population. However, I have begun to do genetic profiles on patients, and have found it to be quite clinically useful.  Beware the tyranny of the anecdote...but I must say I'm a proponent of genetic testing for various reasons, but not always a proponent of the slick genetic testing companies.

The genetic profiles offered now will give you, first and foremost, information about the metabolism of psychiatric medications. How important is this issue? Well, the large STARD trial used the antidepressant citalopram, which is metabolized through the 2D6 pathway. Poor metabolizers (who might experience increased side effects) in this pathway are up to 10% of whites and less so in other races. Ultrarapid metabolizers exist as well (http://en.wikipedia.org/wiki/CYP2D6). The numbers are enough to be important when it comes to establishing how effective the medication might be in a popualtion wide study.

There are genetic polymorphisms in how we metabolize all psychiatric medications, and a genetic clue as to what to expect can be helpful in most people. However, these first level genetics are only one part of the metabolism of medications. We have pharmacogenetics, pharmicodynamics, and pharmicokinetics, and just because you metabolize a medicine as expected does not mean it will work, and it doesn't mean you don't have side effects.

In my use of these genetic tests, I've found some other findings to be more useful than the cytochrome p450 profile. One is if certain medicines are more likely to work (the serotonin reuptake receptor promoter region gene, discussed here) and the methylation profile. In the test I've used the methylation data is limited to the C677t data, but I've been able to turn around some serious longstanding resistant depressions with the addition of methylfolate.

I've been interested in methylfolate in a while, but nothing convinces a person to actually buy and take methylfolate like a genetic profile that says they don't metabolize folate well. Patients who've tried many antidepressants suddenly find they work with the addition of the right folate support in extraordinary ways.

The latest psychiatric magazines and journals are laden with genetic studies. It is the future of medicine. I'm concerned that a company charges $4000 for a pretty report on meds and genome of a few genetic polymorphisms when you can get all your raw genetic data for $99 at 23andme, and the methylation profile for free at geneticgenie.org. Hopefully in the future we can get this vital data for a reasonable price, and use caution to interpret the results.

Sunday, February 15, 2015

Snowed in

Hello there. We've had a record month of snow around these parts, which paradoxically does not make me more productive, but rather makes me want to sit on the couch wrapped in a blanket, sipping tea and doing nothing.

I have a few new posts up despite all of that...some from last month that I'm just getting around to linking here:

Diet, Depression, and the Microbiome

(I've started to use Grace Liu's fiber protocol just as a little self-experiment, btw).

I've FINALLY written something about how exercise affects the brain (it's very positive except when you hit your head with the bar, which I have done more than once in CrossFit), over at the whole9 blog:

Does Exercise Help the Brain?

And last but not least, there is a brand spanking new post at Psychology Today about lifestyle factors and depression based on that wonderful article from BMC Psychiatry:

Lifestyle Interventions for Depression 

Some are obvious, some not so much...like keep those gums healthy!

Look for a new post at the 9 blog soon and I have some other folks requesting blog posts too...I'll get to them when the snow melts, maybe ;-)

In the mean time, just got the brand new book from Diana Rodgers delivered last night, literally on a pile of snow, and I've very excited to try the recipes and projects. Around my house we would need to stand guard with weaponry to keep the animals from eating our garden, but herbs grow very well in the sun room, and maybe we could keep the back porch safe for some pots of garlic and some tomatoes...here's the book trailer for her amazing work full of recipes, home projects, and how to grow your own food at home:


And one final little snippet...I find the following song/music video amazing. It is a dance with a 12 year old girl (the fantastic Maddie Ziegler from Chandelier) and a full grown man (yeah, Shia LaBeouf) in a cage representing two aspects of one person battling mental illness. It's creepy and artistic and powerful, but some may find it too creepy, so fair warning.

Sia: Elastic Heart

Sunday, November 16, 2014

More new blog posts (everywhere but here)

I meant to do even more posts, but I've been down for the count with a horrible cold that felt like a combination of rhinovirus and chikunguna. Finally I'm feeling better, though weak as a kitten. Anyway, prior to the cold I wrote these:

A Gene For Violence (at Psychology Today)

How Food Is Linked to Mood (at Whole9Life)

Earlier today I put out this new post:

Sunshine and Suicide

(Yes, they are linked, but not how you think)

I'm doing a regular monthly column over at Whole9 now, which will be for a more general audience than the biochem-snark ridden curiosities I've been spewing over here since 2010. I think my next one will be about mood and FODMAPS. Let me know if there is anything interesting you want to read about there.

Here's a good song: Kooks Bad Habit.

Oh, I also finished the first draft of another sci fi novel as part of #NoWriNoMo, but the hump of starting book three plus high fever has scuttled my chances of making 50K words this month. C'est la vie. Enjoy your week!

Sunday, October 26, 2014

Magnesium and the Ketamine Connection

Another new post is now live at Psychology Today, discussing how magnesium is a physiologic counterpart to the powerful drug ketamine:  


Folks interested in that may also be interested in the following posts:

The Ketamine Key (this article was Boing Boinged! Hooray)




Have a great week! New Walking Dead tonight...

Friday, October 24, 2014

Ketamine

There's been a bit of upheaval at the house...all will be well, but in the mean time, I'm trying to blog more and get some more clicks over at Psychology Today. Clicks support the writing and research I do and they are much appreciated! There's a new post up about ketamine, the noncompetitive inhibitor of the NMDA receptor that, in one single IV infusion, can alleviate a suicidal depression in about 30 minutes. However, the magic doesn't last, and depression comes back after a week or two. Still, the mechanism and understanding of this phenomenon is important to figuring out the physiology underlying depression.

For right now, ketamine is being used experimentally in hospitals and also in some "salvage" clinics where folks who've responded poorly to other treatments pay for to get a short break from depression.   Other NMDA receptor antagonists might be useful drug targets for experimentation...but to be honest glutamate has been the holy grail neurotransmitter for several psychiatric disorders (schizophrenia, major depressive disorder, and bipolar disorder among them) for the past 20 years, and I've not seen anything come of it, or anything new in the drug pipeline that has panned out.

The supplement NAC utilizes the glutamate pathway via a somewhat convoluted mechanism. I've seen it work for obsessive thoughts, hair pulling (but never for picking behaviors in general) and, interestingly, bipolar depression when every other treatment has already been tried. There's only one study for bipolar depression, but the trichotillomania efficacy is solid and NAC should be part of the clinical arsenal for that symptom.

Here's the post: The Ketamine Key

And here's a new Lorde song I like a lot: Yellow Flicker Beat

Thursday, October 16, 2014

Ketone Esters and Dementia

First off there is a brand new post over at Psychology Today. A new case study was recently published about the use of ketone esters, a supplement that raises blood ketones to levels in humans found only with prolonged fasting. A man with early onset dementia, formerly treated with a ketogenic diet, had lasting improvement on 20 months of ketone esters. Interesting stuff.

A Bold New Experimental Treatment for Alzheimer's Dementia

On the homefront I've been following the Ebola epidemic closely, partially because I have an amateur interest in emerging tropical diseases (I read all those virus hunter books from the 90s), and partially because I went to medical school in Dallas, so I know some of the folks on the front lines, both living in the neighborhoods of the infected and working in the hospitals there.

From what I know, the threat of Ebola (as the virus is now) seems minimal to the general public in the developed world, but it seems abundantly clear after this weekend that ordinary contact precautions (usually gloves, gown, booties, and masks/face shield) in hospitals will not protect the health care workers who are face to face with all those bodily fluids teeming with virus at the sickest stages of the disease. The higher level body suits and meticulous training in PPE (personal protective equipment) found at specialty units and hospitals will be required until everyone gets up to speed.

At the same time, Paul Whiteley tweeted a note from the Lancet with interesting observations about asymptomatic Ebola infections, perhaps quietly immunizing people without causing risk of infections in others.

There's also a terrific Frontline on the Ebola outbreak with all sorts of information about the virus and the experimental drug ZMapp which seems effective (though in very short supply, as in used up for now I think).

Music: Here's the full New World Symphony

Saturday, October 4, 2014

Two new posts over at Psychology Today

Hey there...I know.

Here's a great song: Left Hand Free

The first new post over at Psychology Today is about the big, recently released study shedding some real insight as to how schizophrenia is inherited and what might cause the diseases. It's a game-changer (the findings, not the blog post, though the post was picked as a Psych Today "Essential Read" and "Top Post" for the week).

New Insights Into the Genetics of Schizophrenia

The second new post is about a paper I pulled a while back but never got around to writing up:

Is Gluten Causing Your Depression?

The short answer is...it's possible, but it's probably not causing your irritable bowel symptoms. That's pretty much the FODMAPs if you respond well to a gluten-free diet.

I'm spending a lot of my free time working on a couple of science fiction manuscripts in a far future after most of the population has been wiped out by gluten (kidding! They are wiped out by something else, but I'll have to publish the book for you to find out, probably).

In the mean time, there's a lot of action about gearing up for next year's conferences. I kept a relatively low profile this year, but I've put in a proposal for the American Psychiatric Association Annual Meeting in Toronto, I'm considering PaleoFx in Austin 2015...and I've also been invited to AHS New Zealand, and can't wait to go.