the monotony…

Posted on Tuesday 12 November 2013

From the President
by Steven Hyman, M.D. and Jeffrey Lieberman, M.D.
October 17, 2013

The first two articles in this series addressed the prospect of change in psychiatric medicine and mental health care and the anticipated effects, in this regard, of health care reform. In this article we discuss the current status of biomedical research and how it will impact our field and practice. The research enterprise has brought clinical psychiatry to an exciting but treacherous juncture. Based on remarkable new tools and technologies in genetics and neuroscience, there has been an explosion of new knowledge about the etiology and neural underpinnings of schizophrenia, bipolar disorder, Alzheimer’s disease, autism, addictions, and other serious conditions. Indeed, the fields of psychiatric medicine and mental health care are poised on the brink of transformative advances in diagnostic methods and therapeutic modalities. However, just at the time when biomedical research is gaining significant traction and momentum in understanding the brain and mental disorders, support for all research, and most importantly biomedical research funded by the National Institutes of Health, is painfully contracting, the result of congressionally driven budget cuts. Just as scientific opportunity in our field is waxing, the ability to exploit it is waning…
One aspirational view of how a therapeutic discovery program in psychiatry might look in the near future follows. Enough risk-associated genetic variation will be known for some disorders in five years to put much of the genetic jigsaw puzzle of risk together. [Already in schizophrenia, many proteins have been implicated by genetics that act in the specialized postsynaptic structures of neurons that receive excitatory signals from the neurotransmitter glutamate.] Studies of relevant protein networks in neurons will help identify a subset that could usefully be targeted by drugs; characterizing the genes that encode those proteins would become a priority. Human cells encoding selected genes—both risky and healthy versions—would be engineered into iPS cells. These, in turn, would be differentiated into relevant neurons and perhaps assembled into small circuits. Turner’s actions resulted in harsher slave laws in the South, but also helped push the abolitionist movement in the North. The biochemistry and physiology of cells with risky and healthy versions of the genes could be compared, and then drug screens could be developed that would identify compounds that normalized disease-risk-associated changes. Such drugs would still be studied in animals for toxicity and assessment of behavioral effects. The main difference from our current approach to drug development is that instead of having to guess about which proteins to target with drugs [or as is now the case, sticking with existing targets and hoping for better results], we could allow the genes that are in the causal chain of pathogenesis to point the way. There are no guarantees, and certainly not enough funding for this research, but it truly appears to be a new way and a new day.
Did you notice? About halfway through the middle of the second paragraph, I stuck a random line from an article about Nat Turner’s slave uprising in 1831. Yesterday was the anniversary of the massacre that ended it [here]. It’s pretty interesting. Maybe you’re one of those trained readers who can scan things and your eyes just picked it up. I’m not that kind of reader, but it doesn’t matter, because I wouldn’t have even started reading it. In fact, I spent maybe the last twenty-five years of my career only seeing the Psychiatric News as I shuttled it from the mailbox to the trash. I’m not even sure that I remembered that it was published by the American Psychiatric Association [it kept coming even though my membership lapsed some time in the distant past]. The part I snipped out in the middle of the article was about genetics and stem cells – designed to get you excited enough to clamor for more funding for psychiatric drug research [I couldn't read it all either]. Who reads such articles? Who was it written to? I wonder if Steve Human, former head of the NIMH, and Jeffrey Lieberman, APA President, holed up in a New York hotel for a weekend to get it written suurounded with articles?

Last summer, we spent a few days with old friends in Washington – a Dermatologist I was in training with as an Intern. He was having trouble using his computer to take some CME quizzes. His desk was covered with articles he’d snipped to put in his file cabinets, clinical dermatology stuff – mostly cases – but some research. Now it’s a year later and he’s retired. And then there was a visit to another friend in Jackson Mississippi a year or so earlier – a Gastroenterologist. Another request for computer help to make some slides about recent research on colon visualization using new technologies. He’s finally retired now too in his 70s [yeah, I'm one of those computer guys].  But the point is that on both of those occasions, and many others, I felt vaguely guilty that I wasn’t a medical literature hound [any more]. But the feeling that was even  stronger was a longing. I longed for those days when I was excited to sit down on a break and thumb through my journals. It wasn’t obligation, it was enjoyment. I wanted to do it. And I envied my friends having something to keep up with. I think the reason I’m one of those computer guys is that in those latter years, I thumbed that literature – a displacement activity.

My problem is that I stopped believing in the psychopharmacology articles [for good reason] and things like this [from the above piece] sounded like science fiction [likewise fantastic, at least any time soon]:
These induced pluripotent cells [iPS cells] can be readily differentiated into neurons. Today many scientists are learning how to turn iPS cells or even skin fibroblasts into different types of neurons including those thought to be affected in schizophrenia, bipolar disorder, and autism. Others are collecting skin cells from patients whose genomes have been studied and turning them into neurons for study. Yet others are attempting to turn engineered neurons into small neural circuits to study their patterns of communication with and without disease risk mutations. Circuits might be assembled on a “chip” using small wells etched into an appropriate support or might be assembled in three-dimensional gels. Such technologies are so new that they are not ready for routine application to drug discovery. They are potentially so powerful, however, that a few companies that had abandoned psychiatry are starting up small exploratory programs. 
There wasn’t anything in between. I still feel kind of guilty. It’s no longer because I didn’t read and keep up in the latter years. It’s because I didn’t rise up and shout about what was missing, about the monotony and the poverty of thought. I expect it would’ve been a wasted effort, but I’d feel better now. I didn’t know that a lot of those articles weren’t written by their listed authors, but I feel like I should have. And I feel kind of ashamed that Jeffrey Lieberman and Steve Hyman aren’t writing about the Risderdal® settlement and what it means about the profession…
    Bernard Carroll
    November 12, 2013 | 12:17 PM

    Your samples from Hyman and Lieberman are stupefying… handwaving at its best – or worst. Another good term would be propaganda, created for the purpose of attracting funding. It’s soporific, all right, but I sure noticed your trick with Nat Turner… so my anterior cingulate must still be in good shape. LOL.

    What’s missing here is pathophysiology. Exhibit A for the disconnect between the level of the gene and the cell on the one hand and the level of the person and the illness on the other hand is Huntington’s Disease. We knew the gene around 1982 and we knew the trinucleotide CAG repeat expansion mechanism around 1993 and now, 20 years later, the clinical management of HD hasn’t changed at all except for genetic testing. But there have been no “transformative advances in … therapeutic modalities.”

    November 12, 2013 | 1:57 PM

    It’s also propaganda for the rank-and-file — your ordinary phoning-it-in-psychiatrist who bought the “chemical imbalance” theory before and is now telling patients they have a genetically determined disease, or maybe a diseased brain structure.

    November 12, 2013 | 3:52 PM

    As I normally do, I just plowed into the text until I got to ” Enough risk-associated genetic variation will be known for some disorders in five years to put much of the genetic jigsaw puzzle of risk together. [Already in schizophrenia, many proteins …” Then I looked at the author’s name, thought ‘of course’ and stopped bothering with Lieberman’s drone.

    At times I can’t tell if the trouble I have reading sometimes is due to the lesions in my corpus callossum or if what I’m trying to read is just thick marketing drivel masquerading as an academic work. When I saw what you did there I Iaughed. What brilliant mockery! I laughed, am still smiling, and feel a bit buoyant. Well played, sir!

    Today’s event in glazed eyes and restless reading is Lieberman’s Disorder.

    November 12, 2013 | 6:48 PM

    It’s getting so hard to tell what is real, what is marketing, and what is a joke these days.

    Is this a joke?

    We know that the main target for alcohol in the brain is the neurotransmitter system gamma aminobutyric acid (Gaba), which keeps the brain calm. Alcohol therefore relaxes users through mimicking and increasing the Gaba function. But we also know that there are a range of Gaba subsystems that can be targeted by selective drugs. So in theory we can make an alcohol surrogate that makes people feel relaxed and sociable and remove the unwanted effects, such as aggression and addictiveness…

    All that is needed now is funding to test and put them on the market. A few contacts within the alcohol industry suggest they are interested but do not need to engage until this new invention becomes a threat to their sales. This is a similar situation to that of the tobacco companies when e-cigarettes were being developed. They stood back at first but now own many of the companies making the safer alternatives to cigarettes. Likewise, without investing in a new approach to alcohol, we shall not realise the enormous health potential of a safer alternative.

    The analogy between the effort to change the way the brain responds to alcohol when one’s neurotransmittersare tweaked and the e-cigarette is ridiculous. The e-cigarette is just a vehicle for delivering nicotine to the brain that doesn’t really change the way a brain responds to nicotine in any meaningful way.

    The naked industry involvement is brazen.

    The scientific community is being exceedingly lax about what they consider to have been scientifically validated. These people toying with our brains with no real solid ground to stand on.

    This is an age of a bad research boom that needs to be arrested if these scientists want to, you know, be scientists and all.

    Note the fortune-telling, just around the corner, easy as pie tone that he shares with Lieberman. Nutt has a popular style of writing, but what he’s saying is just as unflippingly unbelievably confident as the shilling articles like the subject of this post.

    November 12, 2013 | 7:27 PM

    Snake oil salesmen. What has changed these couple hundred years?

    The duplicity and cluelessness of alleged government regulatory bodies like the FDA, as a start. Again, who are these people who belong to the APA and support it by such memberships?

    No one with a conscience nor a caring soul, that’s who!

    November 12, 2013 | 8:38 PM

    Loved your Turner insert line–very crafty, but you do have analytic training so I should have suspected you would be smart enough to pull it off! The rest of this Hyman-Lieberman article smacks of a biological psychiatrist’s wet dream. I hope they found pleasure in the “release”, as it were.

    November 13, 2013 | 1:21 PM

    Masturbatory! Exactly.

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