An Update of Some Earlier Blog Posts

There have been some new developments recently concerning some of the issues and stories I have discussed previously on this blog, so I thought I would write a new post that updates some of my previous ones.

First, apropos my post of May 25, Pro-death Florida Legislators Run Amok, about a recently-enacted Florida law prohibiting health care practitioners from even discussing health care concerns about gun ownership with their patents: it was temporarily blocked by Federal U.S. District Court Judge Marcia Cooke. The state plans to appeal the injunction blocking enforcement of the law.

Second, concerning the debate about SSRI antidepressants and whether they are better than placebos:  A Commentary in the December 2011 edition of the American Journal of Psychiatry pointed out that placebo response rates to antidepressants in studies have increased as much as 7% per decade since 1980. 

Not coincidentally, this bizarre inflation of placebo response rates correlates very well with the timing of the rise of the so-called contract research organization, or CRO (http://opp.morningstar.com/PDFs/MOI-EvoCRO.pdf).  These organizations are usually doctors in private practice who are hired by drug companies to do their randomized controlled studies of medications.  These doctors get paid - quite handsomely - for each subject that they successfully recruit for the study. 

The subjects are, in turn, recruited through offers to pay them for their participation. ABC News recently did a story about stay-at-home moms who turn themselves into guinea pigs to earn extra cash. The use of paid subjects has led to the phenomenon of the "professional research subject" who participates in multiple drug trials.

Under these circumstances, both the doctors and the patients are being given cash incentives for exaggerating their symptoms in the initial evaluation so they can qualify for the study!  Once they are picked, no one then has a financial incentive to exaggerate symptoms on follow-up exams.

No wonder placebo response rates have skyrocketed.

CRO Newspaper ad clues in potential research subjects who wish to get paid as to what symptoms to complain about



Last, there are two developments concerning schizophrenia and its treatment with antipsychotic drugs. 

First, as the states have been cutting back on funding for community mental health centers due to the economic downturn, we are seeing a lot of what is described in the following news article:

http://www.freep.com/article/20111127/OPINION02/111270434/After-closing-psychiatric-hospitals-Michigan-incarcerates-mentally-ill-?odyssey=tab%7Ctopnews%7Ctext%7COpinion

After closing psychiatric hospitals, Michigan incarcerates mentally ill

"Wayne County Sheriff Benny Napoleon spoke for most sheriffs when he said, during a community meeting earlier this year, that his jail had become his county's largest mental health care institution.
Over the last two decades, changes in state policy and big cuts in funding for community mental health care have pushed hundreds of thousands of mentally ill people into county jails and state prisons...

"'We closed too many (hospitals), too quickly,' Mark Reinstein, president of the Mental Health Association in Michigan, told me this month. "It wasn't done in a planned, rational way."
Community mental health agencies -- which were supposed to take up the slack but never received the resources to do so -- face continuing budget cuts. The state has resumed warehousing its mentally ill -- this time behind bars...

 "In 1999, a Department of Community Health study -- conducted by Wayne State University -- of jails in Wayne, Kent and Clinton Counties found that more than half their populations were mentally ill and one-third were seriously afflicted, suffering from schizophrenia, bipolar and other psychotic disorders... Since 2008, the state has slashed $50 million from community mental health agencies, with Wayne County absorbing more than half of the cuts.

"Treating one client in a community program costs about $10,000 a year, compared with $35,000 a year to house one prisoner.  Statewide, more than 200,000 people a year use community mental health services, but experts say at least twice that many need them."

To really understand what happens when funding to community mental health centers is cut significantly, one has to realize that fewer patients with schizophrenia will get treated with anti-psychotic medication. Such medication is all the treatment that community mental health centers are providing nowadays.  In addition, those patient with schizophrenia who are seen will be seen much less frequently.  We know from multiple sources that lack of close follow-up highly exacerbates the issue of people not taking prescribed medications (non-compliance).

Off their meds, psychotic patients still end up being incarcerated, but as this story indicates, in jail, not in a hospital. Paradoxically, psychotic inmates are usually then prescribed anti-psychotic medications in prison - at a much higher cost.

One wonders how author Robert Whitaker (Anatomy of an Epidemic), who believes that antipsychotic medications make psychotic people worse, explains away how people with schizophrenia somehow become far more likely to end up in jail when they do not take antipsychotic medication.  Or perhaps he thinks that this development is the result of a malicious government plot .

The question of whether schizophrenia is in fact a real brain disease, and why it has been so hard to pin down the actual pathology, was recently addressed in a newspaper column by neuroscientist  par excellence John J. Medina. 

John J. Medina

An excerpt:

"... a biological explanation for the disease seems heartbreakingly just out of reach. Schizophrenia has a powerful genetic component (heritability percentage is in the low 80s), something I’ve known for years, something that could make it low-hanging research fruit. There is also a large clinical base on which to do studies: schizophrenia afflicts millions of people (the estimated prevalence rate is about 1% of the global population). Despite these seeming advantages, a molecular mechanism capable of describing all aspects of schizophrenia has almost completely eluded researchers.

"There’s a simple reason for this. A deep understanding of schizophrenia at such an intimate level has been hampered by a single technical bottleneck: the lack of a robust in vitro [in the lab as opposed to in the body] disease model.

"That may all be about to change. The results from a study that used cells derived from a deceased patient’s skin tissue has recently been published. Findings from the study may provide just such a model. It is not yet full-fledged schizophrenia-in-a-dish, but the findings portend a powerful future for the field."

Medina then goes on to explain a new technology - a way to produce something called Pluripotent stem cells (iPSC's) which I will not go into here.  Basically, they are re-programmed stem cells.  He then goes on to say:

"With these technologies in mind, I now have the tools needed to understand how to create a dish-bound model of schizophrenia. It involves answering some simple questions: What if you took the skin cells from patients who had schizophrenia and turned them into neurons? Would they exhibit behaviors of typical, healthy cells? Or would they exhibit behaviors reminiscent of previously determined properties of neurons in patients with schizophrenia? If the latter were observed, would you have a robust cellular model of schizophrenia, the missing link in this line of work? A consortium of researchers decided to to find out."

Skin cells from diseased patients made iPSCs that were similar to cells that were obtained from unaffected people.

"The most interesting result came from what happened next. Even though the reprogrammed cells were clearly neural tissue, they did not behave like typically functioning neurons. Several observed differences were eerily similar to previous findings other researchers had seen in tissue samples from patients with schizophrenia."

Despite what you may hear from mental illness deniers, neurons (brain cells) derived from patients with previously diagnosed schizophrenia "exhibit specific, aberrant properties."  I do not wish to get into highly technical neuroscience on this blog, but anyone interested might want to look up definitions for the following terms, and learn about how brain cells from people with schizophrenia differ from those who do not show symptoms of the disorder:

Dendritic arborization,  neuregulin expression, and Global gene expression changes.

After pointing out that this technology does have some problematic aspects to be resolved, Medina concludes: "Having a dish filled with cells that carry many characteristics of a human disease is a lot like having a flashlight in a dark cave. The greatest utility is in the ability to illuminate molecular mechanisms that might go undetected without such a model. It can go a long way toward relieving the frustration often associated with this line of work. Give it enough time and it might even—someday—illuminate a cure."

Undoubtedly, mental illness deniers will find something wrong with any evidence that schizophrenia is a brain disease.  It's in their nature.