Rerun: Is Republicanism the New Stupid?

From Sept, 2010, still relevant ...

"Republicanism isn't a party. It's a diagnosis." A friend of mine happened to relate that to me in a conversation about a year ago, and I have no reason to dispute it. In fact, we actually have the brain science to lend credence to his statement. The same findings also indict Democrats, though I would contend there are mitigating circumstances. It breaks down like this:

It appears that nearly all of us are wired to register moral outrage, but we have very different on and off buttons. The same event can turn us all into avenging angels of God, but for entirely different reasons. A conservative, for instance, might want to kick a beggar. A liberal would kick the person who kicked the beggar.

Yes, environmental factors loom large, but a 2005 NY Times article brought attention to a Virginia Commonwealth University survey of a large sample of identical and fraternal twins on such divisive issues as taxes, labor unions, and x-rated movies. It turned out the identical twin pairs showed much greater concordance on political and social issues than did their more fractious (and apparently less) fraternal counterparts.

We have decades of research to back the proposition that our genetic makeup contributes mightily to our gut-level reactions to all manner of things that go off in the world around us. That same body of research also indicates that our pretenses at reasoned discourse are little more than elaborate justifications for our thoughtless emotional reactions.

In his excellent book, "How We Decide," science writer Jonah Lehrer cites an analysis that found that only 16 percent of voters with "strong party allegiances" during the 1976 US Presidential campaign were persuaded to vote for the other party. In a more recent study, political partisans had their brains scanned as they were read out the on-the-record inconsistencies of George W Bush and John Kerry. Predictably, the prefrontal cortices - the seat of reason - were recruited, which should have been a good sign.

For instance, if exposed to the fact that while on the same day George Bush promised "to provide the best care for all veterans" his administration cut medical benefits to 164,000 veterans, you might expect a Republican to seriously question his or her cherished beliefs. Or at least register some level of primal disgust.

Instead, the Republicans (and Democrats, too, when exposed to stupid Kerry tricks) felt a rush of pleasurable emotion. What seemed to be happening was that the thinking regions of the brain were activated - not to dispassionately weigh the facts and formulate some kind of rational response - but to fabricate a favorable interpretation of the facts, no matter how unpleasant those facts happened to be.

Thus, when the thinking brain had successfully arrived at "mission accomplished" - that is, a palpably absurd conclusion - the lower regions of the brain slobbered like a dog gorging on red meat.

As Lehrer contends, these and many more studies force us to rethink the long-held notion that reason, judiciously applied, overcomes ignorance and blind instinct. Adolph Hitler proved us all wrong on that count.

Now I know why I regard engaging in any kind of dialogue with a Republican as a total waste of time. I came to this unfortunate conclusion back in the nineties, but it wasn't always this way. Before that, I actually cultivated conservative friends. I also worked in a field (financial journalism) which involved total immersion in conservative opinion.

These individuals had a strong influence in my moderating many of my core beliefs and turning me around completely on my more flaky ones. Likewise, I like to think that I exercised a similarly beneficial influence. But in today's highly divisive political climate - the worst in my estimation since the Vietnam era - that simply is not possible. Heaven help if I were to point out to a Republican that Clinton actually turned federal deficits into federal surpluses.

I'm sure Republicans can make similar complaints, but how can I take them seriously when they cite Sarah Palin or Glenn Beck with approval? Hopefully, we can eventually restore reason to the dialogue. In the meantime - forgive me for my attitude - I have to go along with my friend: Republicanism is a diagnosis.

***

I've been very busy with other projects and volunteer work, so beg your indulgence in going with reruns for the next little while.

Brain Science and Recovery - Knowledge is Necessity

My last two pieces - on psychiatrists behaving badly - diverted me from my true mission here at Knowledge is Necessity, namely providing food for thought in the quest of knowing thyself. A very key part of that is passing along any cool brain science stuff I happen to pick up along the way.

Brain science and ancient wisdom represent the crucial double helix in our getting well and staying well. After decades of guess-work psychiatry, researchers have finally figured out how to open up the hood and peer into the brain’s moving parts, and what they are finding out can be applied by us right now in our recovery. I have been shouting this from the roof tops for nearly ten years, and I have no intention of stopping.

My starting point this time is Barbara Oakley’s must-read 2007 “Evil Genes: Why Rome Fell, Hitler Rose, Enron Failed and My Sister Stole My Mother's Boyfriend.” Last week, in Figuring Out Human Behavior, I couldn’t hide my enthusiasm for Dr Oakley’s show-and-tell of the brain science, which paralleled a lot of my research and writing. For both of us, the focus was the serotonin transporter gene, perhaps the most-studied gene related to psychiatric disorders.

To recap: A glitch in this gene predisposes certain people to over-react to environmental stressors, which in turn makes them sitting ducks for depression and other conditions. The breakthrough work came out in the early 2000s, and makes an excellent teaching lesson for a number of points we all need to know, namely:

• Our genes and our environment interact. We may not have any choice in changing our genes, but we can often choose to change our environments in a way that lets sleeping genes lie.
• Genes are not deterministic, but they do predispose us to how we react to whatever life may throw our way.
• Stress is the key driving force in mental illness. There are other factors, but stress is invariably complicit. A good deal of mental illness can be summed up as “stress vulnerability disease.”
• Diagnostic categories useful to a point, but malfunctions in serotonin transport have been linked to anxiety, mania, depression, substance abuse, borderline personality disorder, and all manner of things that can go wrong. Likewise, malfunctions in other processes tend to have similar shotgun effects.
• It is more helpful to think of genes switching on and off certain mechanical processes in the brain than “causing” a specific disease. Moreover, these processes work in the context of whole brain systems interacting with other brain systems, which may exacerbate or mitigate the effects of the equivalent of a tap not being able to shut off.
• There are no “good” genes or “bad” genes. Inevitably, there are trade-offs. A gene variation that may predispose you to stress may also protect you from Alzheimer’s.

To give us a better understanding of the brain in action, it is useful to look at the impact of other genes. Of all things, Dr Oakley’s list and my list are virtually identical. This is no accident. Daniel Weinberger of the NIMH is Oakley’s main source. Likewise, he is mine. Dr Weinberger was part of the team involved in the breakthrough research into the serotonin transporter gene, and he and his NIMH colleagues have been involved with the following, as well:

Brain-Derived-Neurotrophic Factor (BDNF)

This protein is involved in brain cell maintenance and survival and encourages the growth of new neurons and neural connectivity. A “double-val” variation in this gene has been linked to stronger memory. The catch is those with the double-val are prone to more anxiety and moodiness and hostility, possibly due to a magnification of the serotonin transporter glitch. A “double-met,” on the other hand may offset the glitch.

Catechol-O-methyltransferase (COMT)

Mechanically, this gene breaks down dopamine and other neurotransmitters. The more slowly you metabolize dopamine (the “met” variation), the smarter you are. The unfortunate “val/vals” may be a bit less intelligent, with a slightly increased risk of schizophrenia, plus risk of antisocial behavior, and hyperactivity. The “val/mets” fall in between. The trade-off? Vals may be able to handle stress better than the mets and be more flexible to change.

Monamine Oxidase A (MAO-A)

This protein breaks down dopamine and other neurotransmitters. Low-functioning MAO-A has been linked to aggressive and antisocial behavior and substance abuse and more. Those with low-efficiency versions of this gene tend to display hyperactive amygdalae (involved in fight-or-flight) and low-responding orbitofrontal and cingulate cortices. In other words, the front end of the brain has problems turning down the alarm signals from the back end of the brain. Impulsive violence may be one result.

A breakthrough 2002 study found that maltreated kids with low-efficiency MAO-A developed significant antisocial problems while the high-efficiency MAO-A kids were better able to weather the storm.

Wrapping it Up

Don’t worry about understanding all the fine details. The purpose here is to simply display how the interplay between genes and environment affect thinking and feeling and behavior. We are a long way from definitive answers, but we are definitely looking ahead to what 2000 Nobel Laureate Eric Kandel describes as “the new science of the mind.”

We don’t have to wait for psychiatry to get with the program. As I said at the beginning, we can apply brain science to our own recovery right now. Dr Oakley makes it abundantly clear that our behaviors are far less governed by free will and reason than our over-sized egos would have us believe. But knowing that, we can intelligently take stock of our vulnerabilities and make the type of course corrections that allow us more control over our brains and, with it, our lives.

Be smart. Live well ...

Ten Thousand Ways Our Brains Are Messed Up

One of the major stories in bipolar over the past decade is the growing recognition that the condition is way more than a mood disorder. On one hand, we are talking about the thinking cortical regions that fail to boot up properly, even in euthymic (well) patients. On the other, we are talking about the reactive limbic regions that boot up all too well. Too frequently the neural networks that connect the two are severely compromised. Bad things happen.

At the 9th International Bipolar Conference that wrapped up on Sunday, Stephen Strakowski of the University of Cincinnati presented the equivalent of a master’s class.

Above is a representation of the anterior limbic network (ALN). Forget for the time being about specific brain regions and which region is responsible for what. Instead, check out the arrows in the picture that represent how these regions talk and cross-talk with one another. In a 2006 article on CNS Spectrums, Dr Strakowski refers to the old brain science as a “form of phrenology” that wrongly suggested that specific portions of the brain are associated with specific cognitive and emotional traits. Rather:

More recent neuroimaging studies suggest that emotion regulation is an emergent phenomenon that arises out of specific neural networks and that bipolar disorder represents the consequences of dysregulation in these networks.

Okay, let’s see how this works. In a 2004 brain scan study, euthymic bipolar patients performed as well on a simple cognitive task as the healthy controls, but to keep up the bipolars had to activate more brain regions. Dr Strakowski in his talk disclosed he had originally misinterpreted the results. What happened, he said, on later reflection was that the amygdala (which mediates arousal and fear) in the bipolar subjects lit up like a Christmas tree. To compensate for the over-active amygdala, the bipolars recruited the ventral medial prefrontal cortex (VMPFC). Image below.

So, even in routine situations, our brains are subject to stress. And to make up for it, we have to work the thinking parts of the brain harder. No harm, no foul, right?

In another experiment, Stakowski and his colleagues turned up the heat. This time, the subjects were put through a more complex cognitive task called the “counting Stroop,” which involves sorting out incongruent images in rapid succession (such as the number four spelled out three times). In this task, the bipolars scored rather worse than the healthy controls.

Here’s where it really gets interesting. As the task got more difficult, the controls were successful in easing back and slowing down their reaction times, allowing them precious micro-seconds to bring the cognitive areas of the brain online, in particular the regions involved in impulse-control. The bipolars, by contrast, failed miserably in this regard. They kept plowing ahead.

In another study, involving a facial recognition task, Strakowski and his colleagues found difficulties in bipolars in recruiting the VMPFC to suppress amygdala over-activity, resulting in loss of prefrontal control over the brain. In yet another study, the cingulate in the midbrain failed to sort out background noise. On and on it went.

So, imagine yourself in a crowded room this time, not in a brain scan machine. Even the routine task of talking to someone you feel comfortable with may be stressful. Then a stranger sidles over. Meanwhile, you are finding it difficult to tune out a million and one things going on in the room. Everything seems to be closing in. Then your mother-in-law barges in and starts yapping away.

Maybe you rise to the occasion and handle the situation superbly. But you know there is going to be hell to pay some time later. In all likelihood, you will arrive home, either feeling like a wrung-out dish rag or with racing thoughts - or maybe both - needing at least a precious day of recovery time you don’t have. Heaven forbid if you have an important meeting with your boss first thing in the morning.

Obviously, the recovery techniques we have at our disposal help enormously - from the tricks we pick up in cognitive-behavioral therapy to mindfulness to stopping to smell the roses. But when I addressed the panel on the topic of skills training, I was met with blank stares. Here’s where I am coming from:

Two years ago, at the International Congress on Schizophrenia, I happened to walk into a session entitled, "Optimizing Cognitive Training Approaches in Schizophrenia." From a blog piece, Figuring Our Schizophrenia,  I did soon after ...

Translation: The brain is plastic. As Michael Merzenich of UCSF describes it, "Basically, we create ourselves."

The brain is born stupid, then evolves and becomes "massively optimized to fit into your world."

In recognition of this, a relatively new field is opening up that involves drilling patients in cognitive tasks we tend to take for granted, such as holding a thought in our working memory long enough to lay down new neural roadwork or responding to stimuli in a timely fashion.

New computer programs are being developed and being tested on patients, Sophia Vinogradov of UCSF explains, and we are seeing enduring changes in the cognitive performance of patients six months later.

Naturally, I was flabbergasted to find the panelists at the Bipolar Conference wholly ignorant to this, but then again I wasn’t surprised. Despite the fact that the schizophrenia researchers are light-years ahead of the bipolar researchers (aided by infinitely more research dollars) bipolar researchers do not seek them out. Carol Tamminga of the University of Texas, a prominent schizophrenia researcher, was far more polite when she addressed the Bipolar Conference four years earlier, simply referring to the lack of cross-talk between the two fields.

Fortunately, after the seminar, someone sought me out and validated my query, referring to Dr Merzenich and a website involving his work called positscience, which provides some online samples of these cognitive drills. Bipolar is five years behind schizophrenia, my informant acknowledged.

One more point: The studies Dr Strakowski and others perform are designed to catch us at our cognitive worst. These studies are comparatively easy to design and execute. Studies that would catch us at our best - formulating a creative response, thinking outside the box, reaching an intuitive insight - simply do not exist. We know our brains are precision-tooled for this, and researchers such as Nancy Andreasen of the University of Iowa are studying the phenomena very intently. But there is no way to capture the birth of a creative idea in a brain scan machine.

But at least a picture - good and bad - is beginning to emerge of what is going on beneath the hood. And in this type of self-knowledge lies the key to leading more fulfilling lives than we could have imagined when we were initially blindsided by this illness. Be hopeful. Knowledge is necessity.

Is Republicanism the New Stupid?

"Republicanism isn't a party. It's a diagnosis." A friend of mine happened to relate that to me in a conversation about a year ago, and I have no reason to dispute it. In fact, we actually have the brain science to lend credence to his statement. The same findings also indict Democrats, though I would contend there are mitigating circumstances. It breaks down like this:

It appears that nearly all of us are wired to register moral outrage, but we have very different on and off buttons. The same event can turn us all into avenging angels of God, but for entirely different reasons. A conservative, for instance, might want to kick a beggar. A liberal would kick the person who kicked the beggar.

Yes, environmental factors loom large, but a 2005 NY Times article brought attention to a Virginia Commonwealth University survey of a large sample of identical and fraternal twins on such divisive issues as taxes, labor unions, and x-rated movies. It turned out the identical twin pairs showed much greater concordance on political and social issues than did their more fractious (and apparently less) fraternal counterparts.

We have decades of research to back the proposition that our genetic makeup contributes mightily to our gut-level reactions to all manner of things that go off in the world around us. That same body of research also indicates that our pretenses at reasoned discourse are little more than elaborate justifications for our thoughtless emotional reactions.

In his excellent book, "How We Decide," science writer Jonah Lehrer cites an analysis that found that only 16 percent of voters with "strong party allegiances" during the 1976 US Presidential campaign were persuaded to vote for the other party. In a more recent study, political partisans had their brains scanned as they were read out the on-the-record inconsistencies of George W Bush and John Kerry. Predictably, the prefrontal cortices - the seat of reason - were recruited, which should have been a good sign.

For instance, if exposed to the fact that while on the same day George Bush promised "to provide the best care for all veterans" his administration cut medical benefits to 164,000 veterans, you might expect a Republican to seriously question his or her cherished beliefs. Or at least register some level of primal disgust.

Instead, the Republicans (and Democrats, too, when exposed to stupid Kerry tricks) felt a rush of pleasurable emotion. What seemed to be happening was that the thinking regions of the brain were activated - not to dispassionately weigh the facts and formulate some kind of rational response - but to fabricate a favorable interpretation of the facts, no matter how unpleasant those facts happened to be.

Thus, when the thinking brain had successfully arrived at "mission accomplished" - that is, a palpably absurd conclusion - the lower regions of the brain slobbered like a dog gorging on red meat.

As Lehrer contends, these and many more studies force us to rethink the long-held notion that reason, judiciously applied, overcomes ignorance and blind instinct. Adolph Hitler proved us all wrong on that count.

Now I know why I regard engaging in any kind of dialogue with a Republican as a total waste of time. I came to this unfortunate conclusion back in the nineties, but it wasn't always this way. Before that, I actually cultivated conservative friends. I also worked in a field (financial journalism) which involved total immersion in conservative opinion.

These individuals had a strong influence in my moderating many of my core beliefs and turning me around completely on my more flaky ones. Likewise, I like to think that I exercised a similarly beneficial influence. But in today's highly divisive political climate - the worst in my estimation since the Vietnam era - that simply is not possible. Heaven help if I were to point out to a Republican that Clinton actually turned federal deficits into federal surpluses.

I'm sure Republicans can make similar complaints, but how can I take them seriously when they cite Sarah Palin or Glenn Beck with approval? Hopefully, we can eventually restore reason to the dialogue. In the meantime - forgive me for my attitude - I have to go along with my friend: Republicanism is a diagnosis.

More to come ...

Thinking With Our Meat - Part II

Nature/nurture, mind/brain, genes/environment - today’s brain science is providing new insights into how we think and behave. To continue from Part I ...

At the 2003 APA in San Francisco, I heard Daniel Weinberger of the NIMH tell his audience about a study that came out of his lab, published in Science the year before (Ahmad Hariri, lead author). In the study, the researchers rounded up healthy subjects and put them into a brain scan machine (not all at the same time, I presume. I think they lined them up one at a time). The individuals were divided into two groups, those who had a certain variation to a particular gene, what they call the short allele to the serotonin transporter gene, and those who had the long allele.

The serotonin transporter - or serotonin reuptake pump - is the target of SSRI antidepressants. Based on this knowledge, researchers knew there had to be a genetic smoking gun somewhere, but they were stumped. The problem was they were looking for a "depression gene" or a "bipolar gene." Genes, unfortunately, don't code for the way we classify psychiatric disorders.

In 1998, for instance, a German team came to the conclusion that "no association between alleles conveying functional differences in serotonin transport gene expression and major depressive disorder or bipolar disorder could be found."

Basically, genes act as "on-off" switches. But they don't necessarily switch on "depression" or "bipolar" or anything else. Instead, they activate proteins that regulate how cells function and and organize themselves into interacting with other cells. This in turn may influence whether a certain individual is predisposed to depression or bipolar, but you're not going to find that out by looking for a direct link.

It's simple mechanics really. First link the gene to the cellular function it influences. Dr Weinberger and his team already knew that a certain region of the genome, SLC6A4 with the chromosomal address of 17q21, is responsible for the cellular activity that involves vacuuming excess serotonin from the synapse between the neurons.

But then what? What was the connection to behavior? On one hand, Dr Weinberger and his colleagues needed to build on the work of Arvid Carlsson's generation; on the other, they needed to throw away all their preconceptions.

As the study subjects' brains were being scanned, they were made to perform a simple cognitive task involving looking at images of "scary" faces. If you have any doubts about what a two-dimensional image can do to the brain, simply turn on Fox News without the sound. Seriously, just the sight of those idiots - don't get me started.

It turned out that the "short allele" people - that is, those with a certain variation to the gene in question - in reaction to the scary faces, a certain portion of their brains lit up like a Christmas tree. You guessed it, we're talking about the amygdala, which features mightily in my adventures with raccoons and skunks.

As we know, the amygdala mediates fear and arousal, and is directly and indirectly wired into all areas of the brain. Think of the amygdala as a simple smoke alarm. It can detect smoke, but it's too dumb to know whether the smoke is related to grilled meat or a five-alarm fire. The thinking areas of the brain will eventually provide you with the info you need to make a rational decision, but all that takes too way long to boot up.

In the meantime, it's prudent to sound the alarm, even if it is a false alarm. But what if the alarm is over-sensitive or won't shut off? It's one thing for your fight or flight response to kick in at the sight of a predator (or Dick Cheney with a face lift) at the door, but what if you keep having the same reaction to, say, the UPS guy?

When the amygdala goes off, we are reacting rather than thinking. We are operating out of fear. As Dr Weinberger explained to his audience, "this could be the first study to link genes to emotions."

What does this mean?  Let's turn to a closely related study:

About 35 years ago, researchers from the University of Otago recruited a "birth cohort" of more than 1,000 infants born in Dunedin, New Zealand, and subsequently assessed them every two or so years. Had my daughter (who was born in Dunedin) arrived five years earlier, she might have been part of that cohort. Then again, had she been born five years earlier, I wouldn't have been the father.

"Longitudinal" studies of this sort represent the gold standard of population research, as opposed to "retrospective" findings based on recalled events. Over the years, this cohort has been to medical and psychiatric and behavioral research what wild Tanzanian chimps have been to Jane Goodall.

On July 18, 2003, the journal Science published the latest installment coming out of Dunedin. The year before, the same research team had identified certain childhood risk factors in antisocial behavior, together with a strong link to a suspect gene (acting on the enzyme MAO-A). This time, the researchers (Avshalom Caspi, lead author) analyzed the cohort for stressful events over the past five years, such as death in the family, losing a job, or breakup with a partner and this time their attention was directed at the very same gene that featured in Dr Weinberger's study.

Lo and behold, of those meeting the criteria for at least four recent stressful events, 43 percent of the short allele people experienced depression vs just 17 percent with the long allele.

In a field where researchers are accustomed to teasing out frustratingly small statistical blips, these numbers represent something truly seismic.

It is important to note that the researchers did not identify this variation as a "depression gene." Rather, drawing the short genetic straw makes one susceptible to stress and its downstream effects (which may include depression). One also needs to have regard for the fact that not all depressions are caused by stress.

Think of the short allele as a "vulnerability gene." Those with the long allele, by contrast, may be regarded as the proud owners of a "resilience gene."

To further clarify the resilience factor, the depression rates for those with the long allele did not vary, regardless of whether they had experienced zero recent stressful events or four or more. Those with the short allele, by contrast, only experienced this same low depression rate as the long allele people when not exposed to any major stress, period.

As Dr Weinberger described it at a subsequent APA, this particular gene "impacts on how threatening the environment feels." Or, as his colleague Andreas Meyer-Lindenberg put it at yet another conference I attended, the short allele "impairs your ability to respond to what life throws at you."

Noted the Dec 19, 2003 Science: "Together, these studies suggest that the gene variant biases people to perceive the world as highly menacing, which amplifies life stresses to the point of inducing depression."

So, oddly enough, when the Freudian-inspired DSM-I of 1952 fingered "the stresses of interpersonal relations" as complicit in our behavior it was on the right track. Moreover, it wasn't far off in assuming that mental illness was the result of a maladaptation of the individual to his or her environment.

Where Freud's followers went wrong was in thinking that these "neurotic reactions" - to which they assigned a quasi-mystical quality - had little or nothing to do with the meat housed inside our skulls. But that is changing.

More later ...

Thinking With Our Meat

In my previous three blog pieces, I discussed how working on our own various personality issues and behavioral quirks loom large in our recovery. The last piece ended with the proposition that the mind and the brain may be an artificial distinction. To back up my point, I need to backfill the narrative with some brain science (from an earlier piece). Bear with me ...

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 ...

Cool Stuff I Love Talking (and Writing) About

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, 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 (pictured here), 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 literally discovered that dopamine is 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.

Back in those days, scientists were divided into two hostile camps that literally didn't talk to each other - those who believed cells instant-messaged each other electrically and those who thought that chemicals were the prime agents. 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, literally 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.

To be continued ...