Wednesday, November 9, 2011
Daniel Weinberger is a brain scientist at the NIMH. Eavesdropping on brain scientists talking to each other is kind of like overhearing two women having a heart-to-heart coming out of the women’s room - totally unintelligible to outsiders. But this was a psychiatric conference - the American Psychiatric Association annual meeting in San Francisco - and Weinberger compassionately dumbed down his talk. This way, I could almost understand it.
Years later, I would hear Dr Weinberger give a presentation to a room full of fellow brain scientists that included Nobel Laureate Arvid Carlsson and all I could understand were the prepositions.
In a study published in Science in 2002, Weinberger and a team of researchers scanned the brains of healthy individuals as they looked at pictures of scary faces. The scans revealed that those with a certain gene variation - a double short-allele combination to the serotonin transporter gene - lit up like a Christmas tree in a certain part of the brain. That part of the brain was the amygdala - fear central - that kicks off the fight-or-flight response.
As Dr Weinberger explained it, this may have been the first study to link genes to emotions. A few months after hearing the talk, Science published another study examining the same gene variation. This time a research team surveyed a population cohort in New Zealand for recent stressors (such as financial difficulties) in their lives. It turned out that the short-allele people who had experienced high stress suffered way higher rates of depression than the high-stress long-allele group.
(A year earlier, this same research group using similar methodology found a connection to a gene variation that acts on the enzyme MAO - involved in breaking down dopamine and serotonin - and antisocial behavior.)
So - picture me in 2003 as the light bulbs are starting to go off. We have a gene variation that appears to affect the brain in a certain way that makes some of us over-react to stressful situations. And one of the end results is depression.
No, the gene variation did not cause depression. In no way could this be called a depression gene. A stress gene, maybe. Depression was the downstream effect, perhaps just one of many possible downstream effects.
But if you looked at the gene in terms of pure mechanics, it was just a biological unit that switched on something in the brain - in this case the serotonin transporter inside the neuron. The serotonin transporter - or reuptake pump - sucks excess serotonin from the synapse - gap - between two neurons in preparation for another release of the neurotransmitter.
But if the gene responsible for efficient serotonin transporter function isn't doing its job, we have the equivalent of a traffic jam. Bumper-to-bumper serotonin in the synapse. The new serotonin has trouble reaching its destination with its important chemical message.
That message may be trying to tell the other neurons in the brain to calm down, that the situation is OK. But if the message is tied up in traffic, the amygdala - fear central - may be the dominant voice in the brain, sending out a far more alarming message.
But wait - the meat inside our skull doesn’t just operate in a vacuum. It is reacting to what is going on around us. So, if the world out there is just fine, if our lives are just humming along, maybe it doesn’t matter that some rogue gene variation is messing with our serotonin traffic.
It’s amazing how long it took scientists to get this basic point. A PubMed search I did some years back revealed that researchers were hot on the trail of this gene variant at least as far back as 1992. They knew there had to be some mood disorder and other behavior connections somewhere, but the standard gene association studies came up empty.
Basically, to figure out how the gene variant affected behavior, scientists had to tickle it. Expose its owners to stress. As I heard Dr Weinberger explain three years later, this particular gene "impacts on how threatening the environment feels."
By now, the studies were coming in thick and fast. A totally new picture of how our genes and the environment interact and how this played out in the brain and affected behavior was beginning to emerge. The old diagnostic categories - useful to a point - were far too simplistic. So was our conception of biological psychiatry.
I have written on these studies many times, here on Knowledge is Necessity and elsewhere. What caused me to revisit the topic was picking up Barbara Oakley’s 2007 "Evil Genes" two days ago. (See my previous piece, Figuring Out Evil).
“If you ever want to know whether your tax dollars are being used for a good purpose,” she writes, “go take a look at the extraordinary work that the National Institute of Mental Health and other National Institutes of Health are doing in digging out the genetic bases of psychiatric illness.” Dr Weinberger is mentioned often.
It turns out that Dr Oakley and I shared very similar voyages of discovery. The studies I have cited here feature very prominently in her book. She also cites related studies that I have also referred to here and elsewhere, illustrating the vast complexity of the brain as it attempts to simultaneously grapple with the genetic hand it has been dealt and the environment that turns these genes loose.
As I read her words, I found myself re-experiencing the thrill of my awakening that began eight years ago. Call it reverse post-traumatic-stress. The memories joyfully came flooding back. Naturally, I had to write about it.
Much more to come ...
Further reading on mcmanweb: Psychiatry's Big Bang