1 Boring Old Man

Neuroscience, Clinical Evidence, and the Future of Psychiatric Classification in DSM-5
^{by David J. Kupfer, M.D. and Darrel A. Regier, M.D., M.P.H.}
American Journal of Psychiatry 168:672-674, 2011.

^{In the initial stages of development of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders,we expected that some of the limitations of the current psychiatric diagnostic criteria and taxonomy would be mitigated by the integration of validators derived from scientific advances in the last few decades. Throughout the last 25 years of psychiatric research, findings from genetics, neuroimaging, cognitive science, and pathophysiology have yielded important insights into diagnosis and treatment approaches for some debilitating mental disorders, including depression, schizophrenia, and bipolar disorder. In A Research Agenda for DSM-V, we anticipated that these emerging diagnostic and treatment advances would impact the diagnosis and classification of mental disorders faster than what has actually occurred…}

^{The seminal article by Robins and Guze on diagnostic validity, which proposed a classification of psychiatric illnesses based not on psychodynamic, a priori hypotheses but rather on external, empirical indicators, built a direct pathway to DSM-III. Their proposed classification steps included identifying core clinical features, conducting differential diagnosis to separate the condition from similar disorders, gathering laboratory data, assessing temporal stability of the diagnosis, and determining familial aggregation of the disorder. The resultant explicit criteria featured in DSM-III and subsequent editions have significantly improved our understanding of psychiatric disorders, but they did not come without a price. While diagnostic reliability has thrived, large-scale epidemiological studies have underscored the inefficiency of DSM’s criteria in accurately differentiating diagnostic syndromes, especially in community samples. With reification of the criteria through revised editions of DSM-III-R and DSM-IV, proliferation of diagnostic comorbidities and overreliance on the "not otherwise specified" category have continued…}

Research Domain Criteria (RDoC)
National Institute of Mental Health
June 2, 2011

^{Over the past several decades, an increasingly comprehensive body of research in genetics, neuroscience, and behavioral science has transformed our understanding of how the brain produces adaptive behavior, and the ways in which normal functioning becomes disrupted in various forms of mental disorders. In order to speed the translation of this new knowledge to clinical issues, the NIMH included in its new strategic plan Strategy 1.4: “Develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures.” The implementation of this strategy has been named the Research Domain Criteria Project [RDoC]…}

Brain circuitry model for mental illness will transform management, NIH mental health director says
British Medical Journal
by Caroline White
1 September 2011

^{The field of mental health is on the cusp of a revolution, which is set to transform the diagnosis and treatment of mental illness and reverse the lack of major progress made in curbing associated ill health and death over the past 100 years, the director of the US National Institute of Mental Health, has claimed. “We are at an extraordinary moment when the entire scientific foundation for mental health is shifting, with the 20th century discipline of psychiatry becoming the 21st century discipline of clinical neuroscience,” Thomas Insel said before a meeting on the challenges facing mental health research at the Royal Society in London on 31 August…}

^{The seismic shift had been driven by what he described as three “revolutionary changes” in thinking, the first of which was that mental illness was increasingly being recognised as a disorder of brain circuitry, rather than as a chemical imbalance, thanks to neuroimaging techniques and the discovery of some key biomarkers. Secondly, mental ill health was now recognised as a developmental disorder for which early intervention was vital, said Professor Insel, highlighting US research showing that 50% of study participants had reported the onset of mental health problems by the age of 14, and 75% by the age of 24. “We are still stuck with getting to the problem very late. The future will be about understanding the trajectory of illness so that we can identify the first signs before it develops into psychosis,” he said…}

^{Pre-emptive strategies, based on the brain’s plasticity, could include the development of a credible risk score coupled with some, or all of, cognitive training, psychosocial approaches, education, and the use of specially designed video and computer games—a technique that was already being tried out in Australia, he said. But we need to recognise the limits of what we have, he cautioned. “We are not yet at the point of identifying those at high risk as early as we would like.”}

^{The third change was the recognition that mental ill health is a complex mix of genetic and experiential factors. “This is not new,” he affirmed. “But what is new is the ability to probe the genetics of the disorder.” But whether the drug industry will take up the challenge, in the absence of plentiful molecular targets, is unclear, he suggested. “[It] has invested in me too compounds—and sometimes in compounds that are identical to someone else’s. And let’s be frank, that has worked really well for them,” he said. But he declared, “Antipsychotics and antidepressants are not very good.” Much more research into the biology of mental illness was needed, he said.}

^{The consequences of the “remarkable lack of progress” in tackling mental illness effectively were legion, he said. Depression alone was the number one source of disability, he said. “The rate of suicide is way way beyond the rate of homicide in most of the world. In the US, it’s double the rate of homicides and higher than road traffic accidents,” he commented, adding that suicide killed more soldiers in the US military than enemy combat…}

The NIMH has launched an alternative classification project, RDoC, that proposes a research classification based on a matrix of observable behavior and the findings of neuroscience independent of the DSM line of thinking – eliminating traditional categories and reported symptoms from the mix. Dr. Kupfer is taken with that idea and seems to be including some of that information in the narrative sections of the DSM-5.

We already heard from Dr. Stephen Stahl that Drs. Insel and Kupfer were off to London to the Royal Society of Medicine for a meeting, though his report of the meeting topic was somewhat different. Stahl said they were meeting to discuss "the future of new drug development in psychiatry" whereas in the Insel article, it was "the challenges facing mental health research." To each his own, I guess. To my reading, Insel was chiding the pharmaceutical industry for being lazy and taking the safe road by copying existing drugs rather than developing new strategies [I would have preferred another topic for his criticisms].

Dr. Insel’s speech raises his idea of calling psychiatry clinical neuroscience to tectonic heights. We’ve been wrong – mental illness isn’t a chemical issue, it’s in the brain electronics [neuroimaging?]. Solutions aren’t in treatments, they’re in preventive medicine strategies [McGorry?]. And the future is on the genomics side of the endowment/environment equation, and he challenges the drug companies to rise to the task [personalized medicine?]. He concludes with his signature Public Health dirge.

I can’t help being a little sarcastic here. At least I didn’t bring up the part about the Australian computer games or name this post Speculation: The New Generation. I actually like the idea of the RDoC – a research classification separate from our clinical diagnostic scheme. Speculation is the stuff of research, as much a part as experimentation, data collection and analysis. Neuroscience actually has moved along in the last quarter century and deserves a place of its own. When some piece of it reaches clinical usefulness, we can move it into our clinical schema in a heartbeat. Dr. Kupfer doesn’t seem to quite get that point. I guess he’s afraid it’ll get lost – an irrational fear.

My personal reflections on these topics are probably predictable and best reserved for another time. Right now, I want to focus on some mistakes being made here. The first one is glaring. This last epoch has been a time when neuroscience has, in fact, flowered a bit. But what’s on the front burner right now are its current limitations – but even more, the absolutely remarkable trail of pseudoscience, conflicted interests, exaggeration, out-right fraud, and unadvertised drug toxicity. Instead of pointing to the brave new world and future challenges, Insel, Kupfer, the NIMH, Stahl, and anyone else representing the interior of the current psychiatric power base needs to acknowledge these failings and talk about what we’re going to do about them. Failed dreams are the stuff of any movement. We’re not mad about that. But we’re absolutely furious about the collusion with the dark side. Both Kupfer and Insel skirt the elephant in the room. Big mistake! A mistake as big as the elephant they are ignoring. Huge!

Their second error is the same one the psychoanalysts and other mind scientists made fifty or sixty years ago. They had explanatory models that were useful in their areas of origin, but they tried to generalize them to the whole problem of mental illness. They didn’t fit. Instead of highlighting limitations, many stuck to the asset side of the equation [including taking all paying comers as patients]. The results of that mistake are now legend and a lesson for the current neurobiologists. Disillusionment in a period of paradigm exhaustion is a force of often unrecognized fury. Another elephant! As they say, "the bigger they are, the harder they fall."