Psychiatric uncertainty and the neurobiological buzzword

A few years ago I wrote that uncertainty is inevitable in psychiatry.  We literally don't know the pathogenesis of any psychiatric disorder.  Historically, when the etiology of abnormal behavior became known, the disease was no longer considered psychiatric.  Thus, neurosyphilis and myxedema went to internal medicine; seizures, multiple sclerosis, Parkinson's, and many other formerly psychiatric conditions went to neurology; brain tumors and hemorrhages went to neurosurgery; and so forth.  This leaves psychiatry with the remainder: all the behavioral conditions of unknown etiology.  Looking to the future, my fervent hope that researchers will soon discover causes and definitive cures for schizophrenia, bipolar disorder, and other psychiatric disorders comes with the expectation that these conditions will then leave psychiatry for other specialties.  We will always deal with what is left.  At minimum we psychiatrists should accept this reality about our chosen field.  After all, there appears to be no alternative.  Some of us go beyond this to embrace uncertainty as intellectually attractive.  We like that the field is unsettled, in flux, alive. Yet many of us clutch at illusory certainty.  Decades ago, psychoanalysis purportedly held the keys to unlock the mysteries of the mind.  It later lost favor when many conditions, particularly the most severe, were unaffected by this lengthy, expensive treatment.  Now the buzzword is that psychiatric disorders are "neurobiological."  This is said in a tone that implies we know more than we do, that we understand psychiatric etiology.  It's a bluff.

Patients are told they suffer a "chemical imbalance" in the brain, when none has ever been shown.  Rapid advances in brain imaging and genetics have yielded an avalanche of findings that may well bring us closer to understanding the causes of mental disorders.  But they haven't done so yet — a sad fact obscured by popular and professional rhetoric.  In particular, functional brain imaging (e.g., fMRI) fascinates brain scientists and the public alike.  We can now see, in dramatic three-dimensional colorful computer graphics, how different regions of the living brain "light up," that is, vary in metabolic activity.  Population studies reveal systematic differences in patients with specific psychiatric disorders as compared to normals.  Don't such images prove that psychiatric disorders are neurobiological brain diseases?

Not quite.  Readers of these exciting reports often overlook two crucial facts.  First, these metabolic differences only appear in group studies and cannot be used to diagnose individual patients.  As of this writing there is no lab test or brain scan to diagnose any psychiatric disorder.  Attempting to do so would be like diagnosing malnutrition based on height.  While malnourished people are shorter than the well-nourished on average, there is wide overlap and height is not diagnostic.  Second, etiology — the cause of these differences in brain function — remains unknown.  Differences in brain function (and structure) are not necessarily inborn.  Brain anatomy can change as a result of life experience, and metabolic activity (function) from experimental manipulation of cognitive effort, induced mood, guided imagery, etc.  Just as multiple factors affect a subject's height, multiple biological and psychological factors affect brain findings as well.  Thus, learning that patients with borderline personality show decreased metabolism in the frontal lobes (hypofrontality) is neither surprising nor indicative of a neurobiological etiology.  We already know the frontal lobes inhibit impulsive activity, and we already know borderline personality is characterized by impulsivity.  What else would we expect?

Genetic studies consistently show both heritable and environmental factors at play in psychiatric disorders.  Since the 1960s, psychiatry has called this combination the diathesis-stress model: an inborn predisposition meets an environmental stress, leading to an overt disorder.  The model helped shift the field from "nature versus nurture" to "nature and nurture" — and no research discovery or neurobiological rhetoric so far has shifted it back.  Patients and their doctors still contend with diathesis and stress: recreational drug use tips one patient into psychosis, sudden abandonment tips another into borderline rage.  Indeed, clinicians remain much more able to influence stress than diathesis.  A dispassionate assessment of what we currently know should lead to humble agnosticism about psychiatric etiology.  Genetics, biology, and environment all play a role, but beyond that there isn't much we can say.  This is why all current psychiatric medications treat symptoms and are not curative.

In this light, the popularity and zeal of neurobiological language is startling.   The American Psychiatric Association (APA) subtly changed the wording in its new Diagnostic and Statistical Manual, DSM-5, to imply that all psychiatric conditions are biological in nature.  The National Institute of Mental Health (NIMH) assumes that "Mental disorders are biological disorders...."  The National Alliance on Mental Illness (NAMI) says, "A mental illness is a medical condition...."

A more ground-level version is expressed by editor-in-chief Henry A. Nasrallah, MD in the latest edition of Current Psychiatry.  In an editorial not-so-subtly titled, "Borderline personality disorder is a heritable brain disease," Dr. Nasrallah proclaims BPD a "neurobiological illness" and "a serious, disabling brain disorder, not simply an aberration of personality" — as though these were distinct alternatives rather than two terms for the same thing.  After citing a number of biological findings which fail to prove etiology (e.g., the hypofrontality mentioned above) and which show partial heritability, Dr. Nasrallah concludes that "the neuropsychiatric basis of BPD must guide treatment."

Of course, it already does.  We already treat borderline personality disorder the best we know how, with psychotherapy (shown by functional imaging to modify brain metabolism, by the way) and often with adjunctive medication to treat symptoms.  What more do breathless declarations of brain disease buy us, other than reduced credibility?  It's not as though any of us currently withhold neurobiological treatment as a result of outmoded ideology.  On the contrary, the moment the FDA approves a cure for borderline personality disorder based on an established neurobiological etiology, I will gladly refer my patients to the neurologist, virologist, or genetic counselor who would thereafter treat such patients.

Undermedicated

A patient I see for psychotherapy, without medications except for an occasional lorazepam (tranquilizer of the benzodiazepine class), told me his prior psychiatrist declared him grossly undermedicated in one of their early sessions, and had quickly prescribed two or three daily drugs for depression and anxiety.  He shared this story with a smile, as we've never discussed adding medication to his productive weekly sessions that focus on anxiety and interpersonal conflicts.  Indeed, the lorazepam is left over from his prior doctor.  I doubt I would have ordered it myself, although I don't particularly object that he still uses it now and then. Of course, there's a completely innocuous way to explain this difference between his prior psychiatrist and me.  My patient could have looked much worse back then, in dire need of pharmaceutical relief.  However, he didn't relate it to me that way, and I have no reason to doubt him.  There's also the possibility that I'm missing serious pathology in my patient — that I too would urge him to take medication if only I recognized what I'm now overlooking.  But... I don't think so.  I'm left to conclude that his prior psychiatrist and I evaluated essentially the same presentation rather differently.

In particular, I'm struck by the term "undermedicated" (more often spelled without the hyphen, according to my Google search).  This judgment most often comes up in speaking about populations, as in the debate over whether antidepressants are over-prescribed or under-prescribed in society at large, or whether children are diagnosed with ADHD and prescribed stimulants too often, or not often enough.  Under- and overmedication are also commonly mentioned when describing medication management of pain, a thyroid condition, mania, or chronic psychosis in an individual.  Here the terms express disagreement with a particular dosage, where the benefits of treatment and adverse side-effects or risks are deemed out of balance one way or the other.

"Undermedicated" also implies that adding medication is the preferred or only sensible treatment approach.  While this may always be true in hypothyroidism, it clearly isn't with regard to physical or emotional pain.  The term rhetorically denies non-medication alternatives.  I would also add that, to my ear, "overmedicated" and especially "undermedicated" sound dehumanizing, as though referring to a machine that is out of adjustment, or a chemical solution being titrated on a lab bench.  Since the natural state of human beings is not to be medicated at all, it sounds a bit odd to hear someone — as opposed to one's disease — assessed this way.  Perhaps I am especially sensitized to this after reading a controversial article by Moncrieff and Cohen that highlights the "altered state" induced by psychotropics and their lack of known, specific mechanisms of action.  There is often a supposition that medication dosage correlates with symptom relief.  This is not always true of subjective states, underscoring that the complexity of human experience often belies simple "over/under" judgments.

My patient's mood and anxiety vary with his interpersonal situation.  It wouldn't occur to me to turn his "thermostat" up or down in general, even if drugs reliably could do this.  Yet I know colleagues who'd argue that one, two, or even three daily medications could help him overcome his everyday challenges of dealing with people.  These approaches point to different fundamental viewpoints in psychiatry.  Does the patient have a disease, an as-yet-undiscovered chemical (or electrical, viral, inflammatory, etc) imbalance in the brain that is best remedied by a medical intervention, accurately dosed neither "over" nor "under"?  In acute mania or florid psychosis, as in hypothyroidism, it seems to me the answer may be yes, although this is unproven and time will tell.  Perhaps, too, in severe melancholic depression.  But in social anxiety?  Self-consciousness?  Feeling discouraged about one's career?  The field's perspective on these has shifted in recent decades, such that now a hidden biological cause is assumed by default, or at least held out as a rationale for treatment.  It is only by making this dubious assumption that one can speak of undermedicating such complaints, or the people who have them.

Psychiatry as behavioral neuroscience — Sloppy thinking in psychiatry 3

This third installment in my series on sloppy thinking in psychiatry addresses something a little more subtle than "chemical imbalance" or polypharmacy.  It is the growing vision, well represented by this recent editorial in Current Psychiatry, that the only salvation for the field lies in embracing the language and practice of neuroscience.  With "chemical imbalance" discredited, attention has turned to functional brain imaging and genetics as our last and best hope to retain a shred of dignity as a medical specialty.  Dr. Nasrallah's editorial goes further than most, arguing that we need a new name for psychiatry:  Psyche is an "archaic concept" that "has outlived its usefulness and needs to be shed."  Likewise, our "brilliant future anchored in cutting-edge neuroscience" will be hastened by renaming the major mental illnesses, calling psychotherapy “verbal neurotherapy," and by embracing the language of "brain repair."  But it's not all a matter of terminology: "The disastrously dysfunctional public mental health bureaucracy must be abandoned and transformed into 'brain institutes,' in all states, similar to cancer centers or cardiovascular institutes, where state-of-the-art clinical care, training, and research are integrated." I share the sentiment, really I do.  Wouldn't it be great to see shiny Brain Institutes cropping up all over, replacing those sad, underfunded public mental health clinics?  Wouldn't we hold our heads higher if our business cards promised "verbal neurotherapy" and "brain repair"?  We could call ourselves medical doctors without a hint of doubt or insecurity, sit proudly at the hospital cafeteria table  with the other doctors — you know, the surgeons and cardiologists and such — and charge higher fees as a premier medical specialty instead of our current status as mental health "primary care."  There's a lot to recommend this vision; where do I sign up?

Unfortunately, there is nowhere to sign up.  This is a pipe dream.  Psychiatry isn't clinging to archaic language about the psyche out of nostalgia.  It's the best we have.  "Verbal neurotherapy," while technically a valid description of psychotherapy, is absurd hand-waving.  By the same token, taking a vacation is "locational neurotherapy."  We aren't going to gain anyone's respect by dressing up our current practices in pseudoscientific jargon.

Nor are we withholding "behavioral neuroscience" from our patients now.  In addition to the verbal neurotherapy, i.e., psychotherapy, that forms the mainstay of my practice, I also offer pharmaceutical neurotherapy, advice regarding nutritional and exercise neurotherapies, discussion of various occupational and relational neurotherapies — I even suggest an occasional locational neurotherapy.  I simply lack the hubris, or perhaps it's the marketing genius, to call it that.

When scientists develop safe, effective psychiatric treatments based on neuroplasticity and neuroprotection I'll happily offer them to patients (or refer patients to centers where such treatments are available).  When my Election Day ballot includes a measure to upgrade public mental health facilities to state-of-the-art Brain Institutes, you can count on my vote.  I'm not holding my breath.

Kidding aside, there is nothing sloppy or ill-advised about incorporating neuroscience into psychiatry.  Nor is it a new idea.  From prehistoric trepanning to Freud's 1895 "Project for a Scientific Psychology" (pdf of a 2004 review), from the introduction of neuroleptics in the 1950s (modern commentary here) to the "decade of the brain" in the 1990s, psychiatry has nearly always paid homage to the neural underpinnings of behavior.  The only obvious exception was the heyday of psychoanalysis, from about 1950 to 1980.  Otherwise, we use the best neuroscience we have at the time.  The real problem, of course, is that we ask more of our neuroscience than it can deliver.  Trepanning probably didn't help, Freud abandoned his "project," neuroleptics caused major side-effects and failed to allow patients to return to the community, and the "decade of the brain" turned many psychiatrists into drug-doling technicians.  Science keeps improving, and I'm sure we'll see good things emerge in the coming years.  However, progress will occur at its own pace, and no amount of wishing or envisioning will make it happen any faster.

It is sloppy thinking to imagine that behavioral neuroscience is something new and revolutionary.  The real revolution in psychiatry, if it ever happens, will be the integration of careful neuroscience, psychology, sociology, and other disciplines to elucidate and benefit our lived experience.  This integration will incorporate, not supplant, our higher level understandings of psychology and psychodynamics.  When psychiatry is ripe for the "creative destruction" of polarized thinking and choosing sides, it will be stronger than the sum of its parts, and will have finally reinvented itself  into something we can unequivocally be proud of.

And yet again, photo courtesy of Petr Kratochvil.

Chemical imbalance — Sloppy thinking in psychiatry 1

There's a lot of sloppy thinking in my field.  This troubles me.  While psychiatry inevitably deals with the speculative and poorly understood, this surely cannot excuse faulty logic and intellectual laziness.  Worse yet, this laxity of thought extends across the field, from biological psychiatry to psychotherapy, and from the general to the specific.  My next few posts will address what I see as major areas of psychiatric sloppiness. "Chemical imbalance" is a phrase used by psychiatrists and laypeople alike.  When a mental problem seems to arise from within instead of without, it is said to be due to a chemical imbalance.   In truth, however, no chemical imbalance, nor any structural abnormality in the brain, has ever been found to account for anything we currently consider a psychiatric disorder.  Historically, whenever chemical or structural abnormalities were found to account for abnormal mental functioning, those conditions were no longer considered psychiatric and were adopted by another branch of medicine.  If this trend continues, psychiatry will never include pathophysiology in the usual medical sense.  It certainly does not at present.

Like many paving stones on the road to hell, the phrase "chemical imbalance" was sincere and well-intended at first.  It originally referred to the  biogenic amine model of depression, i.e., the hypothesis that a lack of excitatory neurotransmitters such as norepinephrine and serotonin underlies depression.  While it's a fairly compelling concept, it suffers from a lack of solid evidence.  People who are depressed do not have "decreased serotonin in the brain," and taking an SSRI does not "correct" the serotonin level.  Such drugs may offer benefits as a result of boosting serotonin, but that's not because serotonin levels were low to begin with.  Moreover, the fact that SSRIs increase the amount of serotonin in brain synapses says nothing about the ultimate cause of depression.  A cascade of downstream effects follows from tinkering with serotonin, including receptor down-regulation and probably new protein synthesis.  If there's any inherent chemical imbalance being remedied, we don't know a thing about it.

Population studies show subtle changes on average in the brains of patients with certain psychiatric disorders.  However, the findings in subjects with psychiatric diagnoses overlap so much with those of normal subjects that no blood test or brain study can diagnose mental illness in an individual.  (Dr. Daniel Amen claims otherwise regarding SPECT scanning of the brain, but many critics are skeptical.  Likewise, a putative new blood test for depression raises many questions.)  At best, "chemical imbalance" is shorthand for a presumed brain abnormality that no one has yet proven.  At worst, it is disingenuous hand-waving aimed to add medical legitimacy to the field of psychiatry.

Why is "chemical imbalance" so often advanced as a pseudo-explanation for mental illness?  Many psychiatrists confidently proclaim that psychiatric disorders "are medical conditions just like diabetes and hypertension" to justify chronic ongoing management and the need for medication even when the patient feels subjectively well.  Suffering a "chemical imbalance" implies that proper medication will correct a pre-existing, permanent organic abnormality.   The problem here is that the end (patient cooperation) does not justify the means (lying).  The honest answer is that we psychiatrists believe our medications help relieve psychiatric symptoms and distress — although even that is hotly debated — including maintenance treatment to forestall relapse.  This belief is based on outcomes research and clinical, aka anecdotal, experience, not on knowledge of biological mechanisms.

Psychiatry has long been the red-headed stepchild of medicine.  In medical centers we're often in a separate building across the street from the main hospital.  Other physicians sometimes don't understand what we do and make nervous jokes.  Critics accurately note that psychiatric disorders are never found in standard pathology textbooks, and some claim the field is baseless and harmful.  "Chemical imbalance" gives some psychiatrists the medical bona fides they crave, but at the price of intellectual laziness and sloppy thinking.  This serves no one.  Psychiatry must embrace uncertainty, and not seek false security in empty phrases.  Physicians prescribed aspirin for pain and fever long before we understood the intricacies of these conditions, or the mechanism by which aspirin affected them.  We simply knew it worked — no one claimed that a subtle "aspirin imbalance" was being corrected.  Like it or not, psychiatry is in much the same place now.

I'm hardly the first to critique "chemical imbalance," although some still defend it.  I started with this as the prime example of sloppy thinking in psychiatry.  But as we shall see, there are many others.

Photo courtesy of Petr Kratochvil.