Thursday, September 1, 2011

Understanding Schizophrenia

Psychosis gets nearly all the attention in schizophrenia, but that is not necessarily its most prominent feature, according to Cameron Carter of UC Davis (pictured here). Dr Carter keynoted the NAMI CA convention in Sacramento about two weeks ago. Rather, the big concern is cognitive disorganization. Cognitive deficits, he said, involve compromised ability to control our own thinking and behavior.

Thirty years ago, Dr Cameron related, a psychiatrist told him that schizophrenia was not a brain disorder. Rather, it was a psychosis (in the Freudian sense of the term) that could be treated with family therapy. Too bad no one got better.

The first indication that schizophrenia could in fact have something to do with the biology of the brain came more then three decades ago in the form of a breakthrough brain scan study by Johnstone and Crow. The scans, which compared the brains of those with schizophrenia to controls, revealed that those with schizophrenia possessed larger ventricles (open spaces) than the controls. Check out what looks like a butterfly silhouette in the two images below. Notice the decidedly more pronounced butterfly on the right.

Dr Carter recounted reading the Johnstone and Crow study back when it was first published in The Lancet in 1976. “Bollocks!” (a UK term of derision) someone had scribbled in his copy.

More sophisticated imaging studies over the years reveal losses in gray matter volume in different areas of the brain, but this is not the same as loss of brain cells as in Alzheimer's, Dr Carter was quick to point out. All the cells are there. What seems to be going on, among other things, is loss of connectivity (circuitry anomalies, especially in the dorsolateral prefrontal cortex) and neuronal oscillations (particularly in GABA cells). The different regions of the brain, in effect, are out of sync. Thinking gets disrupted.

Dr Carter gave the example of an American tourist in the UK having to negotiate crossing the street. Habitual responding won't do.

But cognitive challenges and psychosis are related, with the first anticipating the latter. Well before psychosis rears its head, it appears that first there are changes in the cortical areas. As these changes progress, this may lead to subcortical dopamine dysregulation and psychosis.

Then there is something called “psychosis risk syndrome.” Thirty to forty percent of those who experience attenuated psychosis features - ie not meeting DSM criteria - go on to develop schizophrenia or bipolar over two years.

So perhaps by improving function in the cortical areas prior to first psychosis, we can prevent psychosis.

This is one of the hot areas in schizophrenia right now. Dr Carter heads up the EDAPT program - Early Diagnosis and Preventive Treatment of Psychotic Illness - at UC Davis. Family involvement, Dr Carter, told us, is the most effective component. New developments include the likelihood of two or three new meds - not antipsychotics or dopamine blockers - that would target cortical areas to improve cognition. Also, cognitive training - pioneered by Sophia Vinogradov of UCSF - based on the “use it or lose it” principle is taking off. Another possibility is transcranial magnetic stimulation.

The brain science over the past five or six years has led to enormous advances in our understanding of schizophrenia. But will our knowledge lead to better treatments and possibly even prevention? Good question.


Smitty said...

The big question is still this, John: Are these images of the schizophrenic brain on drugs?

You are familiar with the European studies a few years back, which showed how the brain actually shrunk in naive patients who had been treated with antipsychotics? I believe the drug was Haldol. The shrinkage was a measurable effect resulting from first time medication.

Smitty said...

And further: a link from an article in the LA Times

John McManamy said...

Hey, Smitty. Off the top of my head, Nancy Andreassen found brain shrinkage attributable to antipsychotics a little while ago. I wasn't familiar with the European studies. I do need to update my website article on antipsychotics in light of this, so many thanks for the reminder.

I don't know if these images are of individuals on meds. It's a very good question.

Smitty said...

I cannot believe Dr. Lieberman said haloperidol is better than nothing, when this is the drug that shrinks the cognitive section of the brain!

John McManamy said...

Hey, Smitty. The link on your second comment - yes, the Andreasen study. Re the Lieberman comment - I'm not ready to condemn him for one remark, especially when we don't know the context. There is a lot of nuance to the "bad drug is better than no drug at all argument," especially if the bad drug is all we've got.

Often, the drug only becomes bad in the hands of an incompetent clinician, and there are no shortage of them.

Smitty said...

Hmm. So you are saying Haldol can be good if in the hands of a good clinician, yet you say such clinicians are a rarity? I'm not sure that makes sense to me.

I'll say this from my own experience: It turned me into a zombie, with a wooden gait. It took my emotions from me, and it also made it impossible to write because my handwriting just got smaller and smaller. And it made my upper back muscles absolutely rigid. And no amount of massage made impact on that. No, and I don't think the big H had any positive effect on my emotional state, and by-the-way, I still had breakthrough symptoms.

Thanks but if I had my choice I would chose anxiolytics first....

John McManamy said...

Hey, Smitty. You got it right. The catch is finding a good clinician and good luck finding one. I'm guessing you got prescribed Haldol because some idiot valued your life at 10 cents, which I think is the unit cost of a tablet.

No doubt, the same idiot also told you that you would have to be on Haldol the rest of your life.

We really are out on are own. Hence the title to this blog.