WHEN SIGMUND FREUD made his only visit to the United States, to give five lectures at a conference at Clark University in 1909, another speaker on the program decried Freud’s new psychoanalytic approach. Edward Bradford Titchener, chair of the Psychology Department at Cornell, found Freud’s concept of the unconscious to be “both foreign to the spirit and inadequate to the status of experimental psychology,” and called his ideas “antediluvian.” Deriving meaning from symbols, as Freud’s psychoanalytic approach does, is itself just a further creation of symbols, Titchener said. Psychoanalysis would have to give way to a modern approach — by which he meant a scientific, experimental one.

From Titchener forward, scientists would take umbrage at psychoanalysis, and psychiatry would be a dispute in search of a discipline.

Disagreement is central to psychiatry, a fact that resonates throughout Anne Harrington’s masterful history, Mind Fixers: Psychiatry’s Troubled Search for the Biology of Mental Illness (Norton, 2019). And the search for a biological basis of psychiatric diagnosis isn’t the only trouble. The entire project of knowing the mind, Harrington shows, is fraught with uncertainty, shaky definitions, conflicting theories, and challenges to authority (on grounds both scientific and religious). Add to that the pharmaceutical manufacturers and their rosy product claims about “well-being.” There’s no peace of mind in psychiatry.

It shouldn’t be a surprise that the nature of the mind has always been a battleground. Unlike Emerson, who writes in The American Scholar that knowing one’s own mind offers a key to the secrets of all minds, Freud knew that no mind can be known fully, not even one’s own. The world is an existentially uncertain place. Not only is the Earth not the center of the universe, but no individual is “master of his own house,” which Freud himself said about the revolution in consciousness he had wrought. With the Freudian concepts of the unconscious, the Id, and repression, the modern era was born. And modernity always gets people jumpy.

Psychoanalysis was meant to be a scientific approach to dealing with mental unease. But Freud’s most important finding was that it isn’t measurement that matters — it’s narrative. Stories make the self. The unconscious secret sanctum holds the true self, but entry is forbidden. Only painstaking analysis of dreams, slips of the tongue, and word associations would afford a narrative that would make sense of our own psychic troubles.

But here is what you can’t do with psychoanalysis: identify a sick brain region, measure chemical imbalances in the brain, sell drugs that will repair faulty chemical balances, cure anyone, or make anyone happy. As Harrington shows, the distaste for the Freudian mind gave rise to a plethora of alternative approaches, from before the Clark lectures to our own day.

The word psychiatry was coined, it’s said, by the German physician Johann-Christian Reil in the early 19th century, from the Greek for “mind” (or “soul”) and “heal.” Reil viewed psychic distress in the framework of then-popular Romantic ideas: madness arising from the increasing distance between Nature and the fallen state of civilized life. Somewhat in the same vein, the French physician Jean-Étienne Esquirol located madness in a separation between the mind’s faculty for reason and its capacity to generate emotional states. In 1818, Esquirol recommended that insanity be treated by specially trained physicians and argued that lunatic hospitals, staffed by physicians, could be instrumental in the treatment of the mad.

In America, treatment of the insane began even before the nation was born. The Pennsylvania Hospital for the mad opened in 1751 and the colony of Virginia started the first public hospital for the insane in Williamsburg in 1773. American asylum inmates were generally supervised by lay custodians (sometimes including drunkards), not physicians — the American asylum until the mid-1800s was a place for behavioral management, not treatment. Where European asylums had often been harsh, at least until Esquirol (and many didn’t improve much even after), the American asylum was a place for relatively benign behavioral management of the nonconforming.

But by the late 1800s, when Harrington’s book opens, scientific revolutions, most especially germ theory and heredity, were turning most of the forbidding old asylums into mental hospitals. Many people, doctors especially, had come to believe that madness must stem not from civilization, as Reil and Esquirol had it, but some fault in the biology of the brain.

Thus, when Charles Guiteau claimed temporary insanity at his 1881 trial for the assassination of President James Garfield, the psychiatrist John Perdue Gray of the State Lunatic Asylum at Utica, New York, said there’s no such thing. If there is no evidence of brain damage, Gray said, then the patient in question, however mad in appearance or action, could not be helped by medicine. No biological damage, no mental illness. Eighty years later, the psychoanalyst Thomas Szasz would make a similar claim in his influential The Myth of Mental Illness. Szasz’s claim, in Harrington’s words, was that “all real medicine […] dealt with diseases, and all real medicine was clear that before something could be specified as a disease, there had to be some evidence of organ malfunctioning.”

It’s easy to look at the Guiteau trial as a metaphor for psychiatry itself, with opposing camps taking positions on the possibility of madness without a verifiable biological basis. But Harrington shows the disagreements to be still more complex.

Harrington recounts the successive attempts by neurologist-psychiatrists to effect cures for psychoses — especially the most difficult sort, labeled schizophrenia by the Swiss psychiatrist Eugen Bleuler. In 1916, at the New Jersey State Lunatic Asylum in Trenton, Henry Cotton began treating schizophrenia by removing allegedly infected organs, including teeth, testes, ovaries, and more, Harrington reports. Infecting patients with malaria to induce fever, a popular treatment in the early 20th century, was soon replaced by shock therapy — using various modes of inducing coma or near-coma: insulin, camphor, the circulatory and respiratory stimulant metrazol (pentylenetetrazol), and eventually electricity. (Electroconvulsive therapy, ECT, eventually moved out of the realm of treating schizophrenia and into the treatment of depression, where it remains.)

The most drastic of the attempted cures for psychosis was lobotomy, created by the Portuguese neurologist Egas Moniz, who was later awarded the Nobel Prize for his work. Lobotomy was popularized from the mid-1930s to the early 1950s in a nationwide crusade by the American psychiatrist Walter Freeman, an avowed opponent of Freudian concepts, and neurosurgeon James Watts. The original procedure involved entering the brain from the side of the skull and surgically severing the neural connections to the brain’s prefrontal cortex. Seeking to make it easier and more accessible, Freeman (apparently over Watts’s objection) pioneered the transorbital lobotomy in 1946: a sharp instrument (an ice pick, in the initial operations) was inserted directly into the front of the brain through the patient’s eye socket.

Lobotomy spread extensively in the early 1950s, Harrington reports, especially to Veterans Administration hospitals eager to find an effective treatment for the many soldiers suffering the effects of exposure to combat horrors. Lobotomy was never fully repudiated — it was just replaced by medication therapy.

The question of biology was highlighted by the advent of drugs for mental illnesses. The full-throated endorsement of medication treatment by mainline medicine, including psychiatry, made it seem that the biological question had been resolved — in favor of the “chemical imbalance” faith. Harrington unpacks the complicated attempts to link human brain chemistry to madness with crystalline clarity, showing just how little evidence there was for chemical fluctuations causing any psychic illness that could be validly and reliably diagnosed.

Psychoactive drugs “cure” an illness that is largely defined by the existence of the drug itself. In the 1950s, imipramine, the first of the so-called tricyclic antidepressants, appeared — based on thin experimental evidence, but bolstered by a new theory that certain -amine and -azine compounds worked on the brain’s neurons to alter “psychic energy.” Later there were the monoamine oxidase inhibitors and so-called atypical antidepressants like bupropion (Wellbutrin). This was the beginning of the era of chemical imbalances as explanations for all sorts of “feeling states.” If worry, anxiety, and melancholia are relieved by drugs, then they must be more than just moods — the chemical imbalance concept turned them into diagnoses.

Diagnostic categories proliferated, and so did the writing of prescriptions to medicate them. In 1968, “depressive neurosis” made its first appearance as a diagnostic category in the second edition of the Diagnostic and Statistical Manual of Mental Disorders the DSM. In the late 1980s, Prozac reached the market, and in 1993 Peter Kramer’s Listening to Prozac was published to great acclaim — followed, Harrington says, by a 15 percent increase in sales of the drug. Within a decade of Prozac’s licensing, the prevalence of diagnosed major depression more than doubled among American adults.

Other conditions showed a similar pattern. Pharmaceutical treatment for anxiety disorder had begun in the 1950s and ’60s with Valium and Librium. Once “panic disorder” had been added to the diagnostic manual, and Xanax (alprazolam) licensed, anxiety diagnoses increased, roughly doubling from 1981 to 2000. Later revisions of the DSM expanded the number of mental diagnoses, increasing, in particular, the ways that depression could be diagnosed. Bipolar disorder in children became a kind of vogue, and so did attention-deficit/hyperactivity disorder, ADHD, and consequent concerns about overmedicating kids with Ritalin, Adderall, and other popular stimulants.

Harrington’s book isn’t an indictment of the pharmaceutical companies, though. There are too many players on the stage of modern mental illness, and the book refreshingly avoids singling out any one as the villain (although the book makes clear that private insurance companies have much to answer for). Mind Fixers even acknowledges a partial upside of diagnostic expansion: “Patients present with acute mental or emotional distress,” Harrington writes, “and doctors look for a DSM diagnosis that will make sense of their suffering. They prescribe drugs because that is what insurance companies will pay for, and because they believe drugs will take the edge off their patients’ distress.” This pattern, however, perpetuates what Harrington calls “the fiction that the drugs they are prescribing are correcting biochemical deficiencies.” But what else is to be done?

To Harrington’s credit, Mind Fixers ends with a proposal for an alternative: a bigger tent. The psychiatric establishment could be sharing power and decision-making with social workers, social service providers, primary-care physicians, counselors, and other sorts of helpers. And with patients. Change the narrative, she urges. Seek a broader and more fully shared understanding of the true range of human suffering.

Overall, though, the story that Mind Fixers tells is a tragedy. So much mental effort, by so many dedicated human beings, has gone into understanding the mind in ways that will keep the “unscientific” Freudian drama at bay. Yet the mind remains a mystery, as Freud said it must. There is so much suffering, all of it real, which is to say experienced by the mind, but not all of it falling into any DSM category. We remain far “from the promised land of real medical understanding of real mental illness,” concludes Harrington. Worse, we remain existentially, vitally unsure of who we are — perhaps more unsure now than ever. We need stories, but we don’t know which ones.

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Philip Alcabes teaches at Hunter College in New York City. He has written a book on epidemics (Dread: How Fear and Fantasy Have Fueled Epidemics) and essays for The American Scholar, VQR, and other publications, and reviews for TLS and LARB. He is working on a book on psychiatric diagnosis and psychoactive medication.