Dr. Insel, or: How Psychiatry Learned to Stop Worrying and Love the Biomarker
A Response to RDoC
It’s difficult to write about psychiatric diagnosis these days. Not only because it’s a scientific quagmire, but also because one risks getting put into a box. Rhetoric in the clinical world is like a strange game of musical chairs where all battle for a coveted but constantly shifting throne called “middle ground” and those without a seat are typecast as reactionaries or “antipsychiatrists” (or even “cynical pragmatists”).
Interestingly, most well-known “antipsychiatrists” rejected the label, because most (but not all) of them were seeking to improve the psychiatric profession, not to destroy it. They critiqued the current model and envisioned new and more accurate ways of defining psychological suffering. This is why —as Jonathan Raskin has poignantly stated— prominent psychiatric researchers have begun to sound so eerily similar to the antipsychiatrists. Their positions are near to equivalent: current system isn’t valid; we need something new that is both scientifically sound and useful for treating patients. The main difference is belief versus doubt in the hypothesis that what we call mental disorder is primarily a disorder of biology. We treat that hypothesis as unfalsifiable, as if the proof arrived before the evidence. We don’t test whether the hypothesis holds; we test whether and how to make the data fit it. When critics raise doubts, they’re often accused of ignoring the very same evidence that psychiatric researchers have recently declared to be utterly insufficient.
How did a scientific discipline come to excommunicate the skeptics and beknight the believers? The answer to that question —historical as it is political— is far beyond the scope of this blog. This text is written hesitantly, with that question in mind, and with the awareness that merely posing it carries a certain risk. But I also write with firm conviction that if scientific psychiatry is and does what it says—as a scientific and academic discipline—critical thinking will find its place within it.
On April 29, a blog post by National Institute of Mental Health (NIMH) director Thomas Insel rocked the psychiatric world with its proclamation that the “disorders” contained in psychiatry’s official diagnostic manual are not actually real.
One might wonder why one man with one brief blog could generate such a seismic wave of press coverage and academic debates (see this, this, this, this, this, this, this, this, this, this, this, this, this, this, this, this, this, this, this, this, this and this). The short answer is twofold: First, blogs and other web-based commentaries are nowadays taken seriously in academic psychiatry, which is so deep in its scientific paradigm crisis that there is little time for the tedious machinery of peer review. And because it’s a paradigm crisis, the means by which psychiatry is currently re-envisioning itself are not only scientific, but also theoretical and pre-empirical. A return to the drawing board, so to speak. These are liminal years for psychiatry, and the blogosphere has become something of an ad-hoc space for dabbling with taboo tools like opinion and basic theory. (Some have even traipsed into that netherworld called philosophy.)
Second, NIMH is the foremost institution for funding psychiatric research in the United States, so its revocation of funding for research based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) is equivalent to telling a fleet of ships that the horizon they’re heading for is actually a cliff at the edge of a flat planet.
It’s also akin to telling patients that we made a huge mistake.
In psychiatry, there’s a term called “insight” that sits somewhere between gossipy buzzword and technical jargon. “Insight” refers to whether the patient attributes her behavior to mental illness —i.e., whether she believes she has the biologically based DSM (or ICD) disorder with which she’s been diagnosed. For at least three decades, “insight” was a signifier for the extent to which psychiatrists and their patients existed within the same interpretative sphere. Preceded by words like “lack of” or “compromised,” it was also a euphemism for “difficult patient.” If a patient lacked insight, she didn’t speak the same language as psychiatrists. She may have rejected her diagnoses outright, or she may have sat with that apathetic look on their face, rolling her eyes or groaning when told to take her Risperdal.
But these days, in psychiatry, it’s not only patients, but a growing number of pre-eminent academic psychiatrists who suffer from a lack of insight into mental illness. This is because many psychiatrists, like Insel, no longer believe in the validity of the disorders they touted for more than three decades. Take Insel’s (2013) example: “The weakness [of DSM] is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. […] Patients with mental disorders deserve better ” (para. 2). Or take a quote by Darrel Regier (2011), Vice Chair of the DSM-5 Task Force: “[…] that’s what the DSM is — a set of scientific hypotheses that are intended to be tested and disproved if the evidence isn’t found to support them” (para. 30).
Today, we might say that it is the patient who doubts her diagnosis who has insight into cutting-edge psychiatry.
The Slovenian philosopher Slavoj Žižek –citing Blaise Pascal’s imperative, “Kneel down and you will believe!”—has argued that religious rituals are performed by proxy— or for a proxy. In other words, the devout kneel down and pray in order to prove —to themselves and to others— that they believe. Paradoxically, this ritual liberates the supplicant from the weighty burden of direct belief itself.
Patients are expected to believe in their diagnoses. We expect them to act like good fundamentalists, performing the prescribed rituals: a pill, an injection, a 50-minute session. In the meantime, we’re busy prognosticating about the dawn of the psychiatric Enlightenment. Our most prominent researchers believe that contemporary psychiatry is comparable to astronomy before Copernicus, biology before Darwin.
Psychiatry’s unicorn is not a heliocentrism or evolution, but something called “biomarkers.” Biomarkers are hypothetical biological markers of mental illness, physiological “things” that would lead to definitive laboratory tests for mental disorders, putting psychiatry on par with the rest of medicine. A recent blog post defending the status quo in psychiatry noted that clinical researchers have been promising biomarkers for at least two decades. Similarly, chair of the DSM-5 Task Force David Kupfer recently said, “We’ve been telling patients for several decades that we are waiting for biomarkers. We’re still waiting.” And if one looks farther back in history, it’s not easy to dismiss the fact that the imminent discovery of biomarkers has been the driving expectation in psychiatry since its birth in the 18th century custodial-cum-lunatic asylums.
So when DSM-5 developers stated they were after a “paradigm shift” that would lead to the discovery of biomarkers , they were repeating a mantra that was not only the basis for Insel’s vision (and the DSM-III/neo-Kraepelinian revolution), but also something that has existed in the psychiatric imaginary for over 100 years.
Perhaps they didn’t read Thomas Kuhn’s observation that scientists tend to toss the previous textbooks to allow for the paradigm shift, or perhaps they just didn’t concur. Or perhaps they were even threatened by the idea that their claims of imminent “biomarker” revelation were no different from those of their professional counterparts one century before.
My first clinical training experience took place at an urban forensic psychiatric hospital, where most of my patients were suffering from what DSM defines as “schizophrenia” and other psychotic disorders. One of my group-therapy patients —”one of the most dangerous,” they said— was a 50-something African-American man who once dazzled the prison SWAT team with his superb defense techniques before they “subdued” him and sent him our way. With us, he claimed to be a divinely appointed prophet who received command messages about entrepreneurial inventions. They ranged from new torture techniques to Sky-Mall gadgets like battery-powered toasters. He was often taken to dramatic antics, holding his dreadlocks in the air while shouting, YOU DON’T UNDERSTAND. I HAVE A CHEMICAL BRAIN IMBALANCE THEY CALL SCHIZOAFFECTIVE DISORDER. A CHEMICAL BRAIN IMBALANCE. DON’T YOU BELIEVE ME? CHEMICAL. BRAIN. IMBALANCE. In staff meetings, behind closed doors, this made the treatment team break into uncontrollable giggles. Our laughter was not only a natural reaction to unsubdued theatricality, but also to our unspoken bewilderment that this man —who’d been homeless and hungry his whole life after suffering under the murderous rage of a crack-addicted mother, herself painfully poor— attributed all of his problems to an excess of dopamine in his brain. (Incidentally, contemporary psychiatrists have nearly abandoned chemical imbalance theories, including the dopamine theory of schizophrenia-spectrum disorders).
But suspicions about primary environmental causes were easily shrugged off. After all, the doxa holds that mental disorder leads to poverty and homelessness, whereas poverty and homelessness cannot cause mental disorder without an underlying biological predisposition. That premise, which remains largely unchallenged, is where Insel and DSM find common ground.
RDoC’s claim is that DSM obfuscated rather than cleared the path towards biomarkers. In other words, biomarkers for mental disorder exist; we just haven’t succeeded in discovering them. There are two problems with this theory. The first is that —though scientific skepticism is an anathema to pre-enlightenment diagnostic psychiatry— clinicians and patients might to think twice before heeding their professional lives to an ancient and unfulfilled promise. The signs of the apocalypse, so to speak, have been there since the dawn of time.
The second problem is a matter of pragmatism: RDoC’s blueprint is no less theoretical than DSM-5. It’s intended to be more empirical, to divide symptoms along the lines of their basic biological dimensions. But one glance at RDoC’s matrix paints a different picture. RDoC’s “symptoms” are not symptoms at all, but units of measurement for psychological processes that are grouped into superordinate “constructs” (an unfortunately chosen term that, in philosophy, denotes a non-empirical concept) and meta-theoretical “domains.”
To be generous, the matrix is no less contrived than that of your standard taxonomy.
The question then becomes: taxonomy of what?
RDoC’s basic units/constructs are, in fact, much more basic, much more measurable than the putative disorder categories listed in the DSM. That’s because the RDoC constructs are essentially no more than basic human emotions and behaviors. “Reception of facial communication,” “goal selection,” “habit,” “visual perception” — these are all normative psychological/neurological processes. Great, but how do they relate to mental disorder?
DSM’s contribution was the codification of clusters, frequencies, and intensities of suffering. It defined mental disorder as abnormal patterns that —depending on which edition you look at— were mental disorders precisely because they disrupted the psychological status quo or functioning in society. That is not to say that this is the way that mental disorder should be defined. The phenomena and thresholds targeted by DSM-5 were historically controversial; nevertheless, they were backed by thoughtful, albeit rudimentary and problematic theories about what constitutes “healthy,” livable mental life. DSM, at least in its more recent versions, defined mental disorder as something that had an impact on interpersonal, societal, and ecological functioning.
That fact deserves repeating: DSM defined mental disorder. Meaning it made some sort of elementary distinction between the subject matter of psychiatry and that of neurology, genetics, and general medicine. If you suffered from X or Y problems for more than Z days in the year, and if these problems caused you distress or trouble at work/home/school, you had a mental disorder. For some disorders, it was sufficient for your relatives to suffer you.
RDoC takes as its basic premise the empirical finding that these DSM-era diagnoses are invented by professional consensus —often substandard, groupthink consensus— and not science. This premise is now commonly accepted. But how will RDoC make clinically meaningful determinations about its theoretical “constructs” and their “domains”? How will research on the neuroscientific and genetic coordinates of “systems for social process” or “positive valence systems” reveal anything beyond neurogenetic coordinates of normal psychological processes?
In other words, how is RDoC anything beyond basic (non-clinical) neuroscience?
Let’s say that, hypothetically, RDoC maps out the precise neurological circuits that underlie fear or loss (two of its “constructs”). And let’s say that this leads to the development of biomarkers, laboratory tests, and new pharmacologic agents for altering the synaptic potentials of somatostain-positive neurons in the central amygdala or enhancing the activity of adrenocorticotropic hormone in the hypothalamic-pituitary-adrenal (HPA) axis. Let’s say that the biomarkers are pathognomonic (for fear and loss responses, respectively), the new tests have near-perfect diagnostic sensitivity and specificity, and the drugs are targeted, safe, and effective.
Let’s say this perfect scenario occurs. It still tells us nothing about whether and when to test and treat a patient. When is fear a mental disorder? Does fear of bears and snakes indicate need for treatment? What about fear of illness? Or the fear a soldier experiences when going to war? And what about loss? Should I seek psychiatric treatment if I lose my mortgage? My wife? My job?
These are the kinds of answers DSM categories, with their clunky and seemingly arbitrary clusters of symptoms, tried to answer. Depression is a “disorder” if it impairs my social or occupational functioning for at least two weeks. But it isn’t a disorder if it occurs within two months of a major loss, even if it has the same neurochemical signature. A phobia is a disorder if I think the fear is excessive and unreasonable, and if the phobic stimulus causes me intense anxiety or distress. But a phobia isn’t a disorder if it doesn’t cause significant distress or impairment. It isn’t a disorder if the stimulus is absent in my environment — for example, if I am afraid of grizzly bears but live in Manhattan. Fear of homosexuals (homophobia) and ethnic “others” (xenophobia) are not mental disorders, even if those fears involve activity of somatostain-positive neurons in the central amygdala.
A whole host of ethical, social, political, and philosophical questions awaits RDoC. The big question is whether and how this new paradigm will define psychiatric disorder. According to the NIMH RDoC website, there are two primary ways in which psychopathology might be identified within the proposed matrix of units of analysis/constructs/domains:
Two general [research] approaches are as follows. The first is to include all patients presenting for treatment at a given type of treatment facility, as in the second example below; the statistical approach then becomes one of regression. The second approach is to specify a particular criterion for selecting multiple groups – e.g., patients who score more than one standard deviation below the mean on a cognitive task, patients who show significant activation in a specified brain area on a neuroimaging task – and compare these to other patients not meeting the criterion and/or to a non-clinical control group.
I’ll address the second suggestion first. RDoC proposes that researchers compare the mean (average) to those that fall above or below it. In other words, RDoC proposes to equate mental health, “normality,” with (statistical) normativity. The closer you are to the mean (average), the healthier you are. This is a standard statistical problem beset by numerous complications, including regression to the mean. It is also a standard social, psychological, and ethical problem. Even if we wanted to believe that normativity is synonymous with health, the research says otherwise. In fact, according to epidemiological estimates, half of Americans will have clinically significant symptoms of a mental disorder at least once in their lifetime. Minority status, on the other hand, does predict the absence of mental disorder — when it corresponds to above-average economic status, above-average intelligence, or above-average education.
RDoC’s primary imperative to researchers is that they should compare clinical groups —those presenting for or already receiving treatment— to controls. This is nothing new; we do the same under the research umbrellas of DSM and ICD. But if RDoC is seeking a new paradigm, it runs into its own special Catch-22: clinical groups are pre-selected —by clinicians and/or the patients themselves— according to DSM (and sometimes ICD) criteria. True, many patients don’t fit standard DSM categories. Yet they showed up for psychiatric treatment because someone —the patient, a family member, or a clinician— recognized that their symptoms were roughly similar to those that fall into psychiatric purview, i.e., the DSM. Moreover, decades of epidemiological research have revealed that “normal” populations are surprisingly “clinical,” so to speak. (The clinical-psych grad students at my old alma mater conducted most of their research on undergrads for precisely that reason.)
As an investigation based primarily on comparisons between groups with and without treatment-seeking behavior, RDoC is less a new means of classifying mental disorder than it is a matrix for differentiating people with and without psychiatric “insight.” Those who interpret their problems in psychiatric language are more likely to seek psychiatric treatment. In other words, most people voluntarily presenting for mental health care typically have some modicum of conviction that their problems might add up to mental disorder.
But not all people presenting for psychiatric treatment do so voluntarily. And researchers who study “insight” know that it would serve as an unfortunate selection criterion for differentiating people with and without psychiatric symptoms. If RDoC specifically targeted unwitting transfers from the general ER, that might be another story entirely. Perhaps RDoC will include patients who lack psychiatric insight, such as patients who were picked up by the SWAT team before they understood anything about their CHEMICAL. BRAIN. IMBALANCE. That would take a mere modification of sampling procedures.
Even if NIMH researchers begin to target patients without insight —first-episode psychosis, let’s say— there’s still an elephant in the room.
The most consistent finding in psychiatric epidemiology is that demographic factors —including SES, gender, age, urbanicity, and unemployment— are our most robust correlates of what we call mental disorder, especially in its more persistent form (see, e.g., 1, 2, 3, 4, 5, 6, 7, 8).
We could suppose that the elephant in RDoC’s room is some as-yet-undiscovered neurocircuit or genetic marker. We could also suppose that it’s a living, breathing animal. As scientists, we might start by examining the evidence.
I wrote this blog in response to Insel’s announcement, which (as described above) shook things up. After the blog was published on NIMH’s website, it took no time at all for the major parties to sort their opponents according to the familiar categories. Same script, different cast. RDoC advocates became the new idealists. DSM advocates, once the idealists, took the reactionary/conservative seat. Those who raise eyebrows at both DSM and RDoC are the new “antipsychiatrists” (see also this). RDoC supporters, DSM supporters, skeptics. One, two, and three.
(1) RDoC is developing a new research model that will undoubtedly yield unprecedented data, but it focuses on the biogenetic correlates and normative mapping of basic psychological processes like visual perception, language, fear responses, and circadian rhythms. The idea is to create interventions for psychological and physiological processes that deviate from the norm. For this reason, RDoC is less likely to save psychiatry than it is to resurrect eugenics.
(2) DSM is probably out of the picture, given a decade or less.
(3) If we’re really to seek a psychiatric Enlightenment, we might return to that great star that guided our scientific forefathers: skepticism. Without it, biomarkers are nothing more than metaphysical conjecture disguised as fact —Platonic ideas. The null hypothesis (that biomarkers are effectively nonexistent unless empirical data says otherwise) will continue to be rejected as blasphemy. In the meantime, there’s a pool of very concrete data that has long been neglected. And those facts we can’t ignore—like the human experience of loss, or fear—will remain scientifically unexplained.
Thomas Insel got it right: patients deserve better.