While we were in Hawai’i, I had a new toy in my pocket – an iPhone. It periodically beeps when an email arrives. I get Google Alerts for a variety of things and this one came on top of a volcano [from a recent Miami Herald]:
Medical studies show a strong correlation between an active lifestyle and lower mortality rates and overall better health. It’s particularly important given our aging population. Recent census data indicate that five Florida cities, including Hialeah and Fort Lauderdale, rank among the nation’s top 10 in highest median age (both with 42.2).
“It really has to do with keeping your mind and body active,” said Dr. Charles Nemeroff, director of the University of Miami Center on Aging and chairman of the department of psychiatry at UM’s medical school. “There is an age-related decline in certain functions like memory that happens to everyone. That’s part of the normal process of aging,” Nemeroff said.
As people age, the number of neurons — the brain’s cells — drops off, Nemeroff said. In fact, the brain peaks somewhere between 25 and 40. “Evidence shows if you keep your brain active as well as your body active, you’re going to be successful in terms of developing your brain. Exercise actually grows new brain cells. So for the elderly who could be losing brain cells, exercise is really important,” he said.
The part of the brain involved in learning and memory, the hippocampus, produces approximately 3,000 to 4,000 new brain cells a day. Engaging in any kind of physical activity for up to 30 minutes daily helps increase production substantially, Nemeroff said…
I don’t question that exercise for the elderly is probably a good idea, but the notion of exercising specifically to increase the hippocampal brain cells and thereby avoiding geriatric memory loss strings things together into a creative story that sounds authoritative, but extrapolates us into the realm of science fiction.
I suppose that that kind of speculation in a fluff piece for a local newspaper is benign – no harm done. But when this kind of thinking appears in our scientific literature, it’s a different story. Here’s another public health appeal in one of Dr. Nemeroff’s classic articles [the one that got him fired from the editorship of Neuropsychopharmacology]:
Major depression is now recognized as a highly prevalent, chronic, recurrent, and disabling biological disorder with high rates of morbidity and mortality. Indeed, major depression, which is projected to be the second leading cause of disability worldwide by the year 2020, is associated with high rates of mortality secondary to suicide and to the now well-established increased risk of death due to comorbid medical disorders, such as myocardial infarction and stroke. Considerable strides have been made over the past 2 decades in the development of safe and efficacious antidepressants. Although truly novel therapies with mechanisms other than monoamine neurotransmitter reuptake inhibition represent an active area of investigation, they are years away from being clinically available. Unfortunately, up to 50% of patients with depression do not achieve remission with currently available treatments in short-term (ie, 6–8 weeks), double-blind, clinical trials…
It’s the lead in to his recommending a Vagus Nerve Stimulator made by a company he and the other authors worked for [he neglected to mention that part]. In fact, he probably didn’t actually write it himself. This paper was from his Sally Laden ghost-writing period. The logic train goes:
Untreated depression causes heart attacks and strokes.
Antidepressants only help half the depressed people.
ergo
Save the other half from disability or an early death with the novel VNS apparatus.
A piece of swiss cheese logic that would have Aristotle and the logicians of old rolling in their graves. But ghostwriter Sally Laden was taken with this public health theme. Here’s another version from an editorial she wrote for Drs. Dwight Evans and Dennis Charney published in Biological Psychiatry elaborating that same theme:
Despite efficacious and widely available antidepressants and psychotherapeutic interventions, the psychosocial and medical burden of depression is increasing. In fact, the World Health Organization projects that depression will continue to be prevalent, and by the year 2020, will remain a leading cause of disability, second only to cardiovascular disease). Although we do not know with certainty why rates and disability associated with depression are increasing, it is likely that this mood disorder continues to be remarkably under-recognized and under-treated. Depression frequently occurs in the context of chronic medical illness, and it is only relatively recently that the research community has turned its attention to the relationship between depression and chronic medical conditions. However, there is much work yet to be done. The recently released Institute of Medicine 2003 acknowledged depression as one of a number of chronic conditions that requires priority action, but did not address the importance of comorbid depression and medical illness. The relationship between depression and medical illnesses is complex. A chronically ill patient who also is clinically depressed may experience enhanced morbidity, a poorer prognosis, and even increased mortality from the medical diagnosis. Simply put, depression makes everything worse. But the association with depression goes beyond the effects of comorbidity on the course and outcome of a medical illness. A burgeoning body of evidence has now demonstrated that the relationship between depression and certain medical illnesses may indeed be bidirectional in nature. Depression may be both a cause and a consequence of some medical illnesses, such as cardiovascular disease, stroke, HIV/AIDS, cancer, and epilepsy…
These are powerful messages that must not be ignored. The weight of evidence is so persuasive that there should never again be a valid reason for not aggressively seeking out and treating depression in medically ill patients. Increasing awareness, reducing stigma, and maintaining a high level of vigilance for depression in medically ill patients must become a priority for clinicians. In addition, the efforts of the research communities must continue to better elucidate the prevalence, risk profile, diagnostic criteria, treatment, and biological underpinnings of the comorbid relationship between depression and medical illness. Only by furthering research efforts and aggressively diagnosing and treating depression, will we be able to achieve substantive gains in health care and in our patients’ quality of life.
In this case, we are being entreated to save lives by treating depression in medically ill patients. There’s little evidence that medications help people with depression in medical illnesses. There is no solid evidence that treating depression prevents or improves medical illness. It’s just another fantasy creation designed to get physicians to prescribe more antidepressants – no scientific basis that I know of. In politics, this is called "spin." The scientific concepts, public health and prevention, are being co-opted to serve the marketing goals of the pharmaceutical sponsors. This "borrowing" of valid science for other purposes extends far and wide. For example, note the use of the word novel in the VNS example above. It’s found repeatedly in the literature, a particular favorite of Dr. Nemeroff. Where does it come from?
CTS: A New Discipline to Catalyze the Transfer of Information
Clinical and Translational Science
by Arthur M. Feldman MD, PhD
21 MAY 2008
Forty years ago, the editors of the New England Journal of Medicine first used the term “bench-bedside interface” to describe the diffusion of information that needed to occur between the clinical arena and the basic science laboratories assessing the biochemical, morphologic, and genetic phenomenon that characterized the phagocytic process in patients with chronic granulomatous disease. This concept of “translating” novel discoveries found at the laboratory bench into the clinical investigation of new technologies and methodologies to both diagnose and treat human disease at the bedside gained increasing focus over the past decade as an explosion of innovative technology supported scientific advances in numerous fields, including genomics, proteomics, gene transfer, stem cell biology, structural biology, and imaging. As these new fields of biology leapt onto the scientific stage, scientists became increasingly aware that the road from the bench to the bedside was not a single lane roadway, but rather a multilane highway that could be traversed in either direction. Indeed, some of the most important discoveries of the past decade have come from observations that were made by investigators in the clinical arena that then stimulated research at the laboratory bench. It was this recognition of the need for a bidirectional linkage between the bench and the bedside that led to the development of a new moniker for this type of research: clinical and translational science…
It’s a catchy idea, Translational Science. The gist of the concept is simple, taking clinical questions into the laboratory, finding solutions, then getting the resulting discoveries or treatments back to the bedside to benefit patients. It specifically refers to the newer technologies ["genomics, proteomics, gene transfer, stem cell biology, structural biology, and imaging"]. What’s not to like about that for a research focus? No more egghead scientists in the lab studying things for their simple love of science. Let’s get our scientists focused on practical solutions to real clinical problems.
"Translational Science" joined "Evidence-Based Medicine" as a buzz-word in psychiatric research. And in psychiatry, "Translational Science" often reduced down to clinical trials of one sort or another. Many grant proposals included a blurb about the urgent, pressing clinical problems addressed by the proposed study. I’ve already mentioned those introductions in articles that quote alarming public health statistics like the morbidity of depression or the comorbid relation of psychiatric illness to physical problems – a standard justification for the poly-pharmacy studies in depression like STAR*D and CO-MED. Note in the piece above from the premier issue of the journal Clinical and Translational Science the phrase "’translating’ novel discoveries found at the laboratory bench into the clinical investigation of new technologies and methodologies to both diagnose and treat human disease at the bedside…" The word "novel" was picked up and added to "Translational Science," "Evidence-Based Medicine," and "Comorbidity" in the vocabulary of a subset of our psychiatric researchers. Novel is used as an excuse for wild speculation that skips necessary basic science underpinnings. Note also the term "bidirectional" in Sally’s introduction and Feldman’s description of Translational Science [in green]. While this last comparison may seem far fetched, I don’t think so. The "concept borrowing" is so rampant as to justify the comparison.
So the notion of "Translational Science" was incorporated in toto by our mental health subset, including the NIMH itself, which is funding Translational Centers and giving out Translational Awards [Tom Insel moved to Director of the NIMH from a Translational Center at Emory – hired there by Dr. Nemeroff]. The Translational idea is, of course, perfect for the psychopharm set because it encourages rapid movement to consumers. Here’s a funded NIMH Grant write-up from Madhukar Trivedi:
The timely selection of the best treatment for patients with depression is critical to the goal of improving remission rates. Due to the biological heterogeneity and variable symptom presentation of depression, it is unlikely that a single clinical or biological marker can guide treatment selection. Rather, a biosignature developed from a systematic exploration of a group of clinical and biological markers is more likely to be successful. Two types of biosignatures are needed to achieve improved outcomes: 1) biosignatures to maximize the selection of optimal treatment for individual patients at the beginning of treatment (moderators) and 2) biosignatures to identify indicators of eventual outcomes early in treatment (mediators). This approach has great potential to personalize treatment and maximize the number of patients who can be treated to full remission with a given treatment. We propose a comparative effectiveness trial of three mechanistically distinct treatments for MDD (citalopram, bupropion, and cognitive behavioral therapy) in which we will assess a comprehensive array of carefully selected clinical (i.e. anxious depression, early life trauma, & gender) and biological (i.e. genetic, neuroimaging, serum, epigenetic & qEEG) moderators and mediators of outcome. Using innovative statistical approaches the identified moderators and mediators will then be used to develop a differential depression treatment response index (DTRI). The proposed study is a randomized two-stage trial (Stagel:12 wks; Stage2: 12 wks) design with 675 MDD patients (with a history of one adequate trial of an SSRI except citalopram) assigned to one of three treatment conditions (n=225 each). This two stage approach is similar to a Sequential Multiple Assignment Randomized Trial (SMART) design. This application brings together researchers with extensive experience in conducting large clinical trials and experts at the forefront of the neurobiology of depression, including: clinical trials (Trivedi, Fava, Schatzberg, Nierenberg, Shelton, Gaynes, Hollon), genetics (Smoller, Binder, McMahan, Perils), neuroimaging (Phillips, Sheline, Etkin, Pizzagalli, Buckner), qEEG (losifescu, Ellenbogen), neurotrophins/cytokines (Duman, Sanacora, Turck, Shelton), clinical predictors (Shelton, Hollon, Trivedi, Fava, Nierenberg, Goodman, Yehuda), neuroendocrine markers (Holsboer, Schatzberg, Shelton, Yehuda), epigenetics (Nestler, Yehuda),and cognitive behavior therapy (Hollon, Manber, Arnow). This team will also be guided by internationally known biomarker scientists (Holsboer, Schatzberg, Krystal, Charney, Goodman), as well as a highly qualified group of biostatisticians (Kraemer, Wisniewski, Schoenfeld). PUBLIC HEALTH RELEVANCE : This study will examine multiple carefully selected clinical and biological markers, using both existing state of-the-art technologies as well as pioneering, innovative approaches. Evaluation of the usefulness of these markers in a trial with three different treatments will assist in generating a depression treatment response index (DTRI). The DTRI will help clinicians match treatments to patients with MDD, resulting in timely selection of treatments best suited for individual patients. Results from this study could significantly improve the treatment of patients with MDD.
Other than using synonyms for novel [pioneering, innovative], this is a "full Monty" import of the Translational Science concept to psychiatry – new technologies en masse brought to bear on the [quaisi] clinical problem of "treatment resistant depression." Trivedi and Rush flunked on "treatment resistant depression" with STAR*D, CO-MED, and TMAP, so Trivedi’s come back with a new version. If one were going to do a shotgun study like this on depression, it would seem like one would use these new technologies to look for biomarkers in depression in general, in hopes of refining the hopelessly broad diagnostic category of MDD [Major Depressive Disorder]. That’s something we need to know. But characteristically, Trivedi’s study skips this important question, and goes straight to treatment choice in "treatment resistant depression." He makes his point explicitly in his comments at the Mayflower Conference held by the Brain Resources company [@ 5:30]:
We have a history of biomarker studies but I think that .?. is very appropriately talking about trying to find some biosignatures for treatment response. And there I think what we have to start focusing on, not so much and I’ve been indirectly saying that throughout in my questions, is that we should not only focus on whether we can predict somebody’s bad outcome or good outcome, because that clinically doesn’t help. If you tell the patient, "bingo you have a bad disease," I don’t think they say, "wonderful doc I’m so glad you told me." So clinically that is a big problem. The second issue is that clinicians have to decide on treatments and therefore the best goal, interim goal at least, we may want to understand the pathophysiology better and I’m not against that, but I think we have to help clinicians decide on one versus the other treatment.
So here we have to add another buzz word – "Personalized Medicine" – borrowed from medicine proper – oncology. Rather than looking at the shaky category of MDD and looking for clarity, Trivedi urges us to skip understanding and move to biomarkers for treatment choices [Celexa vs Wellbutrin vs Cognitive Behavior Therapy]. That’s solid Translational Science – bench to bedside – but it’s hardly science.
I know I’m covering familiar ground here, but there is a point to collecting a few of what could be many examples of perverse science. There is a subset of people in the psychiatric research community who are Pseudoscientists. They have a number of shared characteristics that identify them as a group:
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Academic Positions: They are all well placed in academic positions in prestigious universities, sit on prestigious committees.
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PHARMA Connections: They all have strong ties with multiple Pharmaceutical Companies [lucrative ties].
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Pop Science, Jargon: They borrow popular scientific concepts from other disciplines and each other – quickly learning the lingo and moving from one to the other with ease. They use phrases like Translational Science, Evidence-Based Medicine, Comorbidity, Novel, Personalized Medicine, Alogorithms, Neurobiology of …, Neurogenesis, etc.
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Inflated CVs: They all have CVs listing hundreds and hundreds of articles.
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Single Purpose: Almost all of their research is ultimately oriented towards promoting some marketable product – usually drugs.
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Expensive: They use up an inordinate share of the available research money, public and private.
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Fraternity: They all know each other and frequently appear together as authors or on panels. They frequently quote each other.
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Shared Themes: They are often working on the same things – treatment resistant depression, personalized medicine, pharmacological augmentation, etc.
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Little Scientific Product: While they are listed authors on many papers and frequent speakers at conferences, they have added little to nothing to the enduring scientific record.
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Logic: They are all given to fuzzy logic and rampant speculation bordering on science fantasy. If it might be true, it is often presented as true.
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Wealthy: They are all rich.
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Ethics: All are ethically challenged, at best.
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Notoriety: We all know who they are.
My last post quoted an article asking "Why Does Academic Medicine Allow Ghostwriting?" In the comments, Dr. Carroll asks:
Why does the Society of Biological Psychiatry tolerate ghostwriting? Why does the American College of Neuropsychopharmacology tolerate ghostwriting? Why does the American Psychiatric Association tolerate ghostwriting? Why do these supposedly prestigious professional organizations continue to pander to their corporate supporters and corporate members, even when those corporations have been adjudicated felons
In this post, I want to ask a similar question, "Why has psychiatry allowed itself to be dominated by this fraternity of pseudoscientists?" It’s embarassing, but worse, it’s destroying the credibility and viability of the specialty…
Your commentary is right on target. These impresarios are the flim flam artists of academic psychiatry. Lots of buzzwords, lots of programmatic pie in the sky, lots of promissory notes, lots of symposia organized at international meetings (with Uncle Pharma helping to pay their way), but little progress on the really hard issues. Thank you, too, for pointing out the waste of precious research resources. The synergy that can develop between these weak scientists and an NIMH director like Insel is a net negative for the field.
Speaking of buzzwords, there is no one to compare with Nemeroff. Just read a few of his papers and count how often you find the terms burgeoning, preeminent, concatenation, unique… pseudo-scientific grandiosity anyone?
This to me, is the saddest part: the waste of precious research resources. What COULD have been learned in the last 25 years to help ease human suffering? What COULD have been learned????
Peggi,
Your point is, of course, the only real point – twenty-five years lost…