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Why Are There No Biological Tests in Psychiatry?

This article was published in Scientific American’s former blog network and reflects the views of the author, not necessarily those of Scientific American


Part 5 of a 5-part series

By Allen Frances*

When the third edition of psychiatry’s manual of mental illness, the DSM-III, was published 30 years ago, there was great optimism it would soon be the willing victim of its own success, achieving a kind of planned obsolescence. Surely, the combining of a reasonably reliable system of descriptive diagnosis with the revolutionary new tools of neuroscience would quickly yield a deep and broad understanding of psychopathology. And just as surely this would translate into standardized biological tests that would replace the cookbook listing of subjective symptoms and subjectively evaluated behaviors that comprised the DSM-III criteria sets.


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Sadly, progress has been much slower than anyone expected, with many exciting findings turning out to be no more than dead ends. The vast research funding has indeed provided a basic science revolution, but so far its discoveries have had no impact whatever on clinical diagnosis. Even the most promising candidates—biological tests for the accurate diagnosis of dementia—are several years away. And, for the rest of psychiatry, there is no immediate prospect that our rich basic science knowledge base and powerful investigative tools will contribute to clinical practice any time soon.

We have learned a great deal in the past 30 years, but perhaps the most important lesson is that the brain is ineluctably complex and reveals its secrets only slowly and in very small packages. There has been no low hanging fruit. The expectation that there would be simple gene or neurotransmitter or circuitry explanations for schizophrenia or bipolar or obsessive-compulsive disorder has turned out to be naïve and illusory. The problem of teasing out heterogeneous clinical presentations in psychiatry is compounded by the fact that they also have heterogeneous underlying mechanisms. There will not be one pathway to schizophrenia; there may be dozens, perhaps hundreds. Biological tests that appear to be associated with schizophrenia are never useful for making the diagnosis because they always show more variability within the category than between categories. And seemingly intriguing findings usually don't replicate.

That progress in psychiatric diagnosis is slow should perhaps occasion no surprise. In every branch of medicine, the translational step between basic to clinical science has been difficult. For example, the discovery of genetic correlates for breast cancer has been much more of a slog than originally anticipated, with each advance explaining only a very small portion of the variance. And psychiatry faces the most awesome of translational leaps: the brain is ever so much more complicated than any other body organ, wired with complex redundancies that will defy simple and sweeping explanations of how it generates symptoms and behaviors. For the foreseeable future, except for dementia, we must reconcile ourselves to the staying power of purely clinical diagnosis in psychiatry.

Fortunately, despite all its obvious limitations, the DSM system does the necessary everyday job of fostering clinical communication and providing the foundation for treatment planning and clinical research. Granted that psychiatric diagnosis and treatment are purely empirical rather than based on understanding of mechanism, but this is also true of almost all available medical treatments. The good news is that descriptive diagnosis, when done well, usually leads to psychiatric treatment that is effective and efficient.

But we must also not minimize the grave practical problems and limitations associated with not having biological tests to identify psychiatric disorders. Most troubling is the fact that the overwhelming majority of prescriptions for psychotropic medicines are written by primary care physicians who often have little training in psychiatry; little time to perform an adequate diagnostic evaluation; a tendency to depend on tests rather than talking to patients; and too great a susceptibility to quick trigger diagnosis and poorly chosen pill solutions (fostered by aggressive and misleading drug company marketing). The lack of precise and easily available biological tests in psychiatry permits much loose diagnosing and cowboy prescribing.

And beyond this, a diagnostic system without objective tests is vulnerable to arbitrary changes that can do more harm than good. The furor over the draft of the upcoming edition of psychiatry’s diagnostic bible, the DSM-5, is caused by its radical expansion of the boundaries of psychiatry that will increase by tens of millions the number of people presumed to be suffering from mental disorders. This would be done based on fallible committee decisions, unsupported by solid scientific understanding. Seemingly small and weakly supported changes in the definition of mental disorders can have huge real world impacts, often with extremely harmful unintended consequences.

The safest and most realistic course is to recognize and respect the limitations of descriptive diagnosis. DSM-5 got off on the wrong track because it held the completely unrealizable ambition to provide a paradigm shift. Striving to do the undoable, the framers of the DSM-5 have encouraged recklessly innovative proposals well before their scientific foundation has been prepared.

In clinical psychiatry, as in the rest of medicine, modesty is the best policy and “Do no harm” is the most important injunction. Descriptive psychiatry can serve us well if we don't stretch it beyond its realistic limits.

*Allen Frances, an emeritus professor of psychiatry at Duke University, chaired the task force for the DSM-IV.

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