Originally published on Scientific American’s Blog on April 25, 2017.
In April, JAMA Psychiatry published a groundbreaking addition to its lineup: an educational review intended to educate psychiatrists about neuroscience. A group of psychiatrists led by David Ross of Yale University described how and why post-traumatic stress disorder (PTSD) should be clinically evaluated from a neuroscience framework. The fact that this editorial was published in one of psychiatry’s leading journals is no small feat.
Psychiatry houses a large and powerful contingency that argues that neuroscience has little clinical relevance. The relevance of neuroscience to psychiatry was the subject of a recent op-ed debate in the New York Times: “There’s Such a Thing as Too Much Neuroscience” was rebutted by a letter under the print headline “For More Neuroscience” (“More Neuroscience, Not Less” in the online version). This specific debate—and the dense politics as a whole—exists because competing frameworks are vying for competing funding, a conflict that predates Sigmund Freud’s departure from neurology.
That the relevance of neuroscience to psychiatry is still questioned is blatantly outlandish: What organ do psychiatrists treat if not the brain? And what framework could possibly be more relevant than neuroscience to understanding brain dysfunction?
In the review, Ross and his colleagues tactfully presented their case for neuroscience, describing the obvious choice for a clinical framework as one “perspective,” thus making a delicate intellectual curtsey while supporting their assertions with data.
The researchers discussed five “key neuroscience themes” (read: lines of evidence from burgeoning subfields) relevant to understanding and treating PTSD: fear conditioning, dysregulated circuits, memory reconsolidation, and epigenetic and genetic considerations. Each theme accounts for the diverse biological, psychological and social factors involved in PTSD—which is to say, these factors all have some effect on the brain’s mechanisms. Most important, Ross’s group described how a mechanistic approach allows clinicians to trace the specific causes of PTSD to specific treatments that can target those causes.
The delicate balancing act that Ross et al. performed reflects a conflict between competing clinical frameworks, which, in turn, boil down to two different worldviews: one is intuitive; the other is data-driven. How and why these perspectives clash is better felt than explained. Perhaps I may explain the way I once felt.
The first time I saw a Purkinje cell, I was a high school sophomore in AP Biology. My teacher, Mr. Francom, had just explained that the Purkinje cell is a brain neuron and that, from a central nub, its arms splay throughout the cerebellum, connecting with other neurons. Similar connections throughout the brain formed the hardware for mental phenomena—our abilities to move, think, love, remember, and so on. Experiments and data were involved.
Following this teaser, Mr. Francom slid the Purkinje cell transparency onto the projector with a magician’s élan, revealing an eerie monstrosity: a fluorescent green cell. With its long, dendritic tentacles, it seemed less like something you’d find between your ears and more like The War of the Worlds meets the Kraken.
I’m sure I blurted out, “That thing lets me think?”
The Purkinje cell was an uncomfortable disconnect from my intuition of what makes me me. Were my thoughts and feelings and memories all some extension of a tentacled neuron?
There was a palpable threat to realizing that my mental behavior, the phenomenon of me, was produced by venomous-looking neural hardware—as if someone had pulled back the magician’s sleeve to reveal my own secret, destroying the beauty of my mental life.
Of course, that was just adolescent silliness. The beauty of the brain remains that it actually works, that combinations of lipid membranes, saltwater and proteins actually do produce the love I feel toward my wife or my experience of a sunset while zipping home on my Vespa. And yet it isn’t intuitive at all that this neural hardware exists. Would you have assumed your thoughts came from a Purkinje cell?
Knowledge of the brain’s hardware is even more relevant when things go awry, especially to understand specific phenomena that patients report as symptoms in mental illness.
In a recent Molecular Psychiatry article, Michael Treadway and Chelsea Leonard, both at Emory University, discussed the distinction between a patient’s reported symptom and that patient’s underlying neural hardware, which they referred to as the neural “substrate.” More than a scholastic exercise, this distinction is a clinical tool that allows greater clinical precision because symptoms can have multiple causes.
Imagine it is 3 A.M., and a patient enters the emergency room reporting “chest pain.” The doctors will know that this a serious symptom with many causes and that to treat the patient, they must correctly diagnose and treat the underlying cause. They will immediately examine the patient and order an electrocardiogram to see if the heart’s electrical activity has changed, revealing a heart attack. They will draw blood to look for evidence of heart damage or clot formation. They will order a chest x-ray to rule out pneumonia or a broken rib.
Anxiety is also a cause of chest pain. After ruling out life-threatening causes, the doctors learn that while in the food court at a local mall, the patient broke out in a sweat, her vision blurred and her chest tightened. If she further reports that this happens every time she goes to a large public space, the doctors might diagnose her with a panic attack produced by agoraphobia, a fear of open public spaces.
But consider if our patient recently immigrated from Syria and last year was shopping with her family in a city marketplace when a car bomb exploded. PTSD now becomes the leading diagnosis.
And yet PTSD, agoraphobia and panic attacks are not causes. They are phenomena. Anxiety is a symptom, an anthropomorphism of the phenomenon produced by a network of millions, if not billions, of tentacled neurons firing together.
Ross’s paper helps us understand that patients with PTSD have an overactive sympathetic nervous system, which contributes to symptoms such as hyperarousal, hypervigilance and accentuated startle response, symptoms that can spiral into a panic attack. Further refining our scope to the overproduction of adrenaline in the hypothalamic-pituitary-adrenal axis guides the clinician to prescribe propranolol and prazosin. These medications block aspects of the adrenergic system, thus targeting specific mechanisms that alleviate PTSD symptoms.
Treadway and Leonard would view Ross’s system as substrate-centered, one wherein mental phenomena are followed to, and treated at, their root cause.
Treating a person by focusing on a single receptor—in the case of prazosin, the alpha-1-adrenergic receptor subtype—is not a cold, dehumanizing abstraction. By looking beyond the phenomena of our inner experience to the Purkinje cells hard at work, we can create a pragmatic, nuts-and-bolts method of understanding and healing ourselves.
Plus, studies show that it works.