Friday, November 6, 2009
If you're a serious researcher wanting to know more about your field, you don't waste your time attending the annual meeting of the American Psychiatric Association. The week-long meeting is largely regarded as a junket where clinicians can pick up the CME credits they need to remain in good professional standing.
But if you know what you're looking for, you can learn a hell of a lot. In eight years of APAs, I've had the honor of listening to three Nobel Laureates, plus numerous others who deserve a free trip to Stockholm. I particularly enjoy hearing the brain scientists, who are kind enough to dumb down their presentations for the psychiatrists, which means people like me can kind of follow along.
Here's how it works: When Daniel Weinberger of the NIMH is at the APA and happens to mention the COMT Val 108/158 Met variation (don't ask), he pauses to explain what that means. Not only that, he has cool PowerPoint slides that even psychiatrists and Geico cavemen can follow. When the same Dr Weinberger is at, say a schizophrenia research conference, addressing an audience that includes 2000 Nobel Laureate Arvid Carlsson, he doesn't even bother to let on what the COMT Val-Met variation is all about. He just assumes everyone knows. And forget about a cool PowerPoint.
Research conferences don't intimidate me. Remember, raccoons respect my piss. In San Diego in 2009, at the International Conference on Schizophrenia Research, I approached a table where very smart people were drinking their morning coffee, and introduced myself as the only C student at the table. The line worked so well I used it the rest of the day. It didn't take me long to get into the spirit of this particular conference, and soon I was referring to my coffee as my "neuro-cognitive starter."
Naturally, I knew exactly what to say to the likes of Dr Carlsson. Being a journalist, I assumed a totally professional demeanor and introduced myself as someone about to become a grandfather who would like to thank his son-in-law for his participation in the effort - who happens to be a neurosurgeon in training - if he (Dr Carlsson, that is) would be so kind as to provide an autograph.
Dr Carlsson, to his credit, smiled indulgently, and graciously signed the back of my program. His co-Laureate, Eric Kandel, did the same for me a few years earlier at the APA in Atlanta when I told him about my nephew who is as smart as Einstein. "I really admire your work," I burbled to Dr Carlsson, as my parting remark. I'm sure that was the high point of his life, coming from a C student.
A little background: Dr Carlsson discovered that dopamine was a neurotransmitter. Finding a new neurotransmitter was to brain science what the discovery of Uranus was to astronomy, only far more significant. At least, back in William Herschel's day, we knew what a planet was and what it did. By contrast, as late as the early 1960s, we had only the vaguest idea how brain cells - neurons - communicated.
So for Dr Carlsson to even arrive at the concept of neurotransmitter and dopamine, first he and his contemporaries had to figure out the Newtonian physics of that mysterious inner universe we call the brain.
We now take it for granted that a neurotransmitter is a packet of chemicals that is delivered from one nerve cell across a gap (or synapse) to another nerve cell. The neurotransmitter glutamate, for instance, instructs neurons to get excited. It's all about chemicals outside the brain cell setting off chemical reactions inside the brain cell (after first being assembled inside a different brain cell). Technically electricity is also involved, but we don't need to go there.
Had Dr Carlsson stopped right there, he certainly would have earned his plane ticket to Stockholm. (Wait, Dr Carlsson is Swedish - he probably only had to drive across town to collect his prize, assuming he could find a place to park.) But no, Dr Carlsson connected dopamine deficiency in the brain to Parkinson's, which led to L-dopa and other agents for its treatment, thereby significantly improving the lives of countless millions.
That isn't the end of the story. Dr Carlsson's discovery literally opened up the field of biological psychiatry, which posits that - hello! - the brain is not undifferentiated tofu. You can argue till the cows come about whether the mind and brain are the same or two entirely different entities, but when all is said and done, how we react to the environment around us and how we anticipate our future is mediated through the elegantly intricate processes of the meat housed inside our skulls.
We think with our meat. Newtonian meat, quantum meat, highly specialized units of meat, 100 billion cells - as many as the stars in the Milky Way - arranged in infinite connections switched on by some 16,500 genes out of a total of about 25,000 in the human genome.
So when I told Dr Carlsson I admired his work, I really meant it. Not only that, I was in awe of it. I would have felt the same way had I a chance to shake Einstein's hand. So - seriously - I didn't mind at all that I looked like a fool. Every day, when my very smart son-in-law is conferring with neurologists and prepping for surgery with a precious life hanging in the balance, he is literally performing his work in the very considerable shadow of Dr Carlsson. And now he has Dr Carlsson's autograph hanging from his wall.
So here was Dr Carlsson, in the audience at a schizophrenia research conference, listening to Dr Weinberger, part of a new generation building on his work. It didn't take researchers long to figure out that an oversupply of dopamine is involved in schizophrenia and that an emotionally and cognitively stable brain has a lot to do with dopamine in "just right" amounts.
But the brain isn't just chemical soup. It's not simply a matter of splashing in a bit of this and a bit of that into a bubbling broth. Cells organize themselves into extremely complex systems, which in turn interact with each other in unbelievably sophisticated and subtle ways. It's more helpful, instead, to think of the brain as a computer, or - even better - as all the computers in the world connected with each other through the internet.
We can also think of the brain as an ecosystem.
At its most rudimentary level, we are talking about the primitive and reactive parts of the brain communicating with the highly sophisticated thinking parts of the brain. In certain situations, if the communication is too efficient, irrational thoughts dominate the internal dialogue of the brain. In others, if the communication is inefficient, rational thoughts fail to get through.
The COMT Val-Met variation that Dr Weinberger was talking about is involved in this process. COMT is an enzyme that influences dopamine transmission in parts of the prefrontal cortex. From a treatment standpoint, a "smart" dopamine med that targets COMT to influence dopamine in a specific region of the brain may be a far safer and more effective way to treat schizophrenia and other mental ills than our current generation of meds.
I first ran across Dr Weinberger at the 2003 APA in San Francisco, in relation to a gene that influences a different neurotransmitter, serotonin. I was an innocent, about to have my eyes opened ...