Thursday, April 2, 2009

Figuring Out Schizophrenia - Part III


Yesterday was the last day of the International Congress on Schizophrenia Research, held in San Diego. A brief recap of my third day there:

Early morning: My brain has clearly not booted up, not even after two coffees. I sleepwalk into the main hall for a lecture on "The Hidden Life of Genes: Endophenotyping Schizophrenia," by David Braff of UCSD, the year's recipient of the Congress' prestigious William Warren Award (that's Dr Braff pictured).

I've already given you a major hint into endophenotype: Me, with bipolar, with major difficulty regulating my sleep, which seriously interferes with my ability to function. The general population also experiences sleep disorders, but clearly sleep is tied into my illness.

Thus, rather than look for illness-specific genetic needles in haystacks, it may be more constructive to seek out more common and obvious bio-markers (such as sleep) and work one's way upstream or downstream from there.

Dr Braff was writing about endophenotypes back in the seventies, but it is only within the last five years or so that the topic has really taken off. For instance, Dr Braff explains, patients with schizophrenia experience major problems in sensory gating, ie screening out irrelevant stimuli (such as a noisy ventilation system) which plays havoc with their ability to focus on relevant stimuli (such as a conversation).

What we are finding, according to Dr Braff, is a clustering of patients around various different endophenotypes (eye movement - saccades - involving reaction time is another). Thus, one drug is not going to fit all. The next generation of meds, he says, need to be far more specific.

Schizophrenia, Dr Braff concluds, is a malignant terrible disease that is not going to give up its secrets readily. Instead, we "have to conquer schizophrenia gene by gene, step by step."

Late morning: "Optimizing Cognitive Training Approaches in Schizphrenia," reads the title to this two-hour symposium. Translation: The brain is plastic. As Michael Merzenich of UCLA 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.

Afternoon: Today's poster presentation has a treatment theme, and here there is a clear disconnect from the rest of the conference and earlier poster presentations. Pharma is out in force, with products based on 50s technology. An example:

I stop at a J&J poster testing Invega on a schizo-affective population. No surprise, the antipsychotic knocks out the psychosis. Invega is son of Risperdal, which in turn is a descendant of Haldol.

See what I'm driving at? The emphasis of current schizophrenia research is on cognition and the underlying biology. Psychosis is what gets patients in trouble, but difficulties thinking is what keeps them from winning back their lives. Pharma has nothing in its current inventory for this, but they're still in a state of denial pretending that they are still relevant. (Think Detroit, only not nearly as smart.)

So here is J&J, pitching a med with roots in the 1950s, with a study designed for no other purpose than to milk its current patent. I ask some of the other researchers about this and get a lot of nodding heads and knowing looks.

If only these researchers were running Pharma, I can only think. The good news: Everywhere, Pharma is clearly losing both its influence and credibility. The bad news: In another year or two, we are going to know J&J as makers of baby powder and other fine consumer products. Same with the other drug companies.

Where, then, are the new smart meds going to come from?

Much more in future blog posts ...

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