Tuesday, January 31, 2012

Robert Whitaker: Dangerous in America

On his Mad in America blog, in a Jan 12 post Rethinking Brain Research in Psychiatry, Robert Whitaker, author of "Anatomy of an Epidemic," made the very legitimate point that brain studies on those with mental illness fail to account for the effects of exposure to psychiatric drugs.

Agreed. So, if you slice and dice the brains of deceased individuals with schizophrenia and bipolar and compare them to “healthy” brains, as scientists at the Scripps Institute very recently did, and find that DNA “stays too tightly wound” in the brain cells of schizophrenia subjects, is the effect attributable to the illness, as the researchers suggested, or to the meds the patients have been on all these years, as Whitaker argues needs to be controlled for?

Furthermore: If we can’t say for sure, is the study actually worth the paper it’s printed on? No to everything, says Whitaker most emphatically. “First, let’s look at this particular study,” says Whitaker, who then does not look at this particular study. What Whitaker fails to mention is the study’s real finding and its implications: that a certain gene regulation process observed in neurological disorders also has a correlation to schizophrenia.

The study, published in Translational Psychiatry, sheds very important light on the developing field of epigenetics, which is rewriting the entire book on genetics. If you haven’t heard of epigenetics, don’t worry - you will. I first reported on the topic back in 2004, when a PubMed search listed but one author researching bipolar from an epigenetic perspective. Now epigenetics is emerging as the main event. Last year, I heard Jonathan Sebat of UCSD talk about “copy number variants” in schizophrenia and autism.

Back to the study: The devastating effects of the acetylation of histones (which appears to drive the “tightly wound” DNA dynamic) is the narrow story. The insights the study sheds into the dynamics of epigenetics is the wider story. Both together add up to the real story. Here is the scientific gobbledygook from the research article:

The major findings from this study are: (1) histone ac-H3K9K14 levels are correlated with gene expression levels for several schizophrenia-related genes, including GAD1; (2) age is strongly negatively associated with promoter-associated histone acetylation levels in normal subjects and those with bipolar disorder, but not schizophrenia and (3) histone H3K9K14 levels are hypoacetylated at the promoter regions of important genes in young subjects with schizophrenia.

Maybe another group of scientists will discover that psychiatric meds are involved in the histone acetylation process, but a further study would require funding, and here Whitaker has his own agenda.

Whitaker says the researchers at Scripps could have “administered neuroleptics to healthy rats.” Huh? This was an epigenetics study, not a drug company pre-clinical trial. Does Whitaker even know the difference? Has Whitaker even heard of epigenetics?

“This is why I think it is time for the NIMH to reallocate its research dollars,” says Whitaker. “Decades of such brain research has not produced any notable therapeutic payoff.”

And it is an absolute certainty that there will be no payoff if propagandists such as Whitaker have their way. For there to be any kind of therapeutic pay-off, first we need to find out what is really going on in the brain. NIMH research has led the way in busting old myths (ironically, Whitaker relies on this research in Anatomy of an Epidemic) and has totally changed how we think about brain function and mental illness.

But it also reveals how little we truly know. Alas, there are no easy answers. All the low-hanging therapeutic fruit has already been plucked. Research is badly underfunded, especially with no short-term pay-offs in sight. Today's research efforts are for the benefit of future generations. That's what civilization is all about. We work, we sacrifice, for those who come after us. But there are no guarantees in the frustrating and noble quest for knowledge.


kimbriel said...

John, the point is that these same "brain changes" observed from "schizophrenia" can also be found in primates who are administered neuroleptics. That has been shown time and again. Researchers don't account for it, even though it's basic. It's getting to be where I don't think it's a case of anything more than willful blindness.

My concern is more pragmatic. We can't have all these people going out on disability due to mental illness. The system wasn't designed for it, and the system is crumbling. I do agree that science is important, but all the science research we've done in the last 50 years has only resulted in more and more people claiming disability due to mental illness. Disability claimant rates for all other disabilities over the same time period have fallen slightly. It's time to look at how we can get most of these people in jobs and occupations. The current mode of investigation isn't doing that. We can't continue to afford barking up these same old trees.

John McManamy said...

Hey, Kimbriel. I acknowledge the point that brain scientists should not be willfully blind to meds changes in the brain. Let's have a conversation on this. If sweeping changes are called for let's advocate for the sweeping changes. But let's leave Whitaker out of it.

Daniel B said...

Thanks for this analysis. I think in order to appreciate Whitaker's claims and when (or if) they are valid, we need to divide up what results might be affected medications and what results couldn't be.

I'm unfortunately an expert in the brain, but a clear explanation by brain scientists (is that what they're called) of why medications couldn't affect certain outcomes would really blunt Whitaker's criticisms.

John McManamy said...

Hey, Daniel. I fully agree. At the very least, authors of these studies should be obligated to mention:

Option one: "We have controlled for the possible effect of psychotropic medications etc etc

Option two: "It was not possible to control for the possible effect of psychotropic medications. These are our reasons for hypothesizing why our findings are nevertheless valid. ..."

Option three: "It was not possible to control for the possible effect of psychotropic medications. This is indeed a confounding variable. More research is needed ...

If brain science were to cave into Whitaker's demands, there would be no brain science. In a bipolar or schizophrenic population virtually everyone has been on meds. Yet we need to do fMRIs.

A lot of what we know from brain scans - NIMH-funded - has come from healthy subjects. But then we need to follow up with scans on those with various psychiatric diagnoses.

Yes, we have a problem, but Whitaker's solution - to not perform these studies - is absurd.

But yes, let's have the conversation.