Tuesday, March 31, 2009

Figuring Out Schizophrenia - Part II

Another full day at the International Congress on Schizophrenia Research, here in San Diego. To recap:

Breakfast: Beatriz Luna of the University of Pittsburgh tells me she isn't a schizophrenia researcher. Rather, she's into something called "development." I'm thinking development, as in a child psychologist.

No, she tells me. This is about brain development, as in the child brain maturing into the adult brain. She will be one of the speakers at a two-hour symposium later in the morning. (That's her in the photo.) Curious, I check it out:

Think of research into normal brain development shedding valuable light on schizophrenia, and, by extension, all of mental illness. The first speaker, Patricio O'Donnell of the University of Maryland, talks about cortical microcircuits and the balance between excitation and inhibition. Dopamine, he says, plays a large role in the modulation of circuits in the prefrontal cortex. During adolescence, he explains, these circuits experience dramatic connecting changes.

For instance, "phasic dopamine" (firing in bursts) gets dialed in, with improved signal to noise ratios.

But suppose the brain doesn't mature? Are we then looking at an approximation of schizophrenia?

David Lewis of the University of Pittsburgh shows slides that highlight the neuron's "dendritic spines." These spines play a major role in brain cells talking to one another. We know that people with schizophrenia are not favorably endowed in this category, but what does it mean?

In normal brain development, he explains, there is an early dramatic increase in spine density followed by a dropping off in adolescence and leveling out in adulthood. But are we talking about a drop-off in "functionally mature" or "functionally immature" connections? In other words, when the brain experiences structural changes, are the right chemical messages crossing the dendritic divide or the wrong ones?

Early intervention, he says, might be directed at enhancing the normal development of these synapses.

Dr Luna informs the audience that adolescence involves major risk of mental illness. As she explained to me over breakfast, this is when the brain changes gears. But what if something goes wrong in the transition? Might this underlie the pathology of mental illness?

During adolescence, the brain undergoes "synaptic pruning," along with axonal "myelination." In essence, brain function becomes more equally distributed, with less reliance on impulses from the basal ganglia and other more primitive regions of the brain.

But what if something goes wrong? Normal child brain function is suddenly not so normal, not in an adult brain anyway. You can kind of see this with the current economic meltdown, Dr Luna explains. It's a new world. AIG and GM and the rest can't behave the way they used to. The failure in executive behavior in this new context, she concludes, now becomes obvious.

Lunch time posters: This is where I get to ask all my stupid questions. For instance, over the past two days, the area of the brain I've been hearing most about is the dorsolateral prefrontal cortex, the brain function I've been hearing the most about is working memory, and the researcher I have been hearing most about is Joseph Callicot of the NIMH.

"Allelic Variation in KCNH2 is Associated with Dorsolateral Prefrontal Cortex Activation During Working Memory," reads the poster.

The name tag on the man standing in front of the poster reads Joseph Callicot.

Knock me over with a feather. Fire away with all your stupid questions, says the look on his face.

I love this job ...

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