Delusion's Chemical Source

 

“The Madness Pill

 

By Justin Garson

 

St. Martin's, 240 pages, $30

 

Well into the 1950s, many psychiatrists regarded schizophrenia -- a mental illness with myriad symptoms that range from full-blown psychosis to disordered thought and social withdrawal -- as an incurable manifestation of the patient's unconscious conflicts, childhood trauma and stalled mental development.

 

That view was challenged by scientists who investigated the biology of psychotic thinking. As Justin Garson writes in "The Madness Pill: One Doctor's Quest to Understand Schizophrenia," the effect on psychiatry was like "the Copernican revolution in physics." The debilitating onset of psychosis was "no longer the start of an inner journey. It was a brain disease."

 

Among the medical pioneers responsible for the breakthrough was Solomon H. Snyder. As a college student in the late 1950s he'd been inspired to become a psychiatrist after reading Sigmund Freud's work. But he soon became disillusioned with the psychodynamic account of mental illness advanced by Freudians and looked instead to the brain's chemistry for answers.

 

His dedicated interest in schizophrenia began while he was a medical student at Georgetown in the early 1960s and grew during his time as a researcher at the National Institutes of Health. By 1970, as a professor at the Johns Hopkins University School of Medicine, Dr. Snyder had devoted himself to identifying the brain receptor for the neurotransmitter dopamine. His pursuit of the biological basis of schizophrenia -- and his quest for a pharmaceutical treatment for the disease -- is the subject of Mr. Garson's engaging scientific biography.

 

Dr. Snyder began by weaving together evidentiary strands collected by other investigators in the 1950s and '60s. Among the most important came from Arvid Carlsson's work establishing dopamine as a major neurotransmitter. Another was the discovery that Thorazine, the first antipsychotic medication administered to schizophrenic patients, had been shown to block dopamine activity -- and, in so doing, melted away delusions and hallucinations.

 

Around the same time, Mr. Garson explains, researchers identified "amphetamine psychosis" in habitual users of stimulants -- and in humans and animals given amphetamines in the laboratory. Many of its symptoms were virtually identical to the delusions of paranoid schizophrenia. Scientists noted, too, that amphetamine bore a chemical resemblance to dopamine, adding further weight to the connection between dopamine and schizophrenia.

 

Drawing on these findings, Dr. Snyder hypothesized that naturally occurring psychotic episodes were likely caused by high dopamine levels in the brain. But how did dopamine exert its effect? The answer, discovered in 1975 by Dr. Snyder and one of his graduate students, Candace Pert, was a cellular site -- a receptor -- to which dopamine attached. Effective antipsychotic medications, they argued, were those that blocked these dopamine receptors.

 

Psychiatry's embrace of Dr. Snyder's finding was foreshadowed by a convergence of pre-existing forces. "Psychiatrists were fed up with psychoanalysis and longed to be seen as part of a valid medical profession," Mr. Garson writes. "Patients were tired of being told that their debilitating psychological problems were caused by childhood traumas or bad parenting." The pharmaceutical industry, meanwhile, was eager to create "the next blockbuster drug, something on the order of Thorazine and Valium."

 

Mr. Garson makes the case that Dr. Snyder's research into dopamine and mental illness "sculpted science's overarching understanding of how such drugs work." His findings would eventually pave the way for new types of psychopharmaceuticals, including selective serotonin reuptake inhibitors (SSRIs), such as Prozac (fluoxetine), as well as second-generation antipsychotic drugs.

 

To Dr. Snyder's credit, his concerns went beyond the molecular. As a psychiatrist, he was mindful of the whole person who was suffering -- not merely a disordered brain. This compassionate perspective runs through his many books, including "The Troubled Mind: A Guide to Release From Distress" (1976), in which he presented psychological strategies for coping with depression and anxiety.

 

Now 87 years old, Dr. Snyder is a professor emeritus at the Johns Hopkins University School of Medicine. "The Madness Pill" is a vivid and affectionate tribute to a brilliant scientist, though, the author writes, one who "is almost unknown outside of scientific circles." Mr. Garson, a professor of philosophy at the City University of New York, has written previously on mental illness, and the opening pages tell us why the topic captivated him. When Mr. Garson's father, John, was working as a trade lawyer in the Nixon administration, John became convinced that the Washington Post was reporting on his activity -- through coded references he believed he could spot in the paper.

 

The elder Garson's initial delusions resolved, but later returned and were treated with antipsychotic medications. These subdued the psychosis but produced a mental fog that affected his ability to work and demoralized him profoundly. Side effects caused difficulty in motor control and swallowing. "But the voices were gone," Mr. Garson reports. "His doctors considered his treatment a success."

 

While Dr. Snyder's dopamine hypothesis was a scientific milestone, it turned out to be incomplete. We now know that additional neurotransmitters are involved in schizophrenia. Most scientists today view it as a neurodevelopmental disorder, and clinicians debate whether the protean manifestations of schizophrenia are all part of a discrete biological phenomenon.

 

Medications that target dopamine receptors offer hope to many suffering from psychotic disorders, but there are serious limits. As many as 30% of current schizophrenic patients derive little benefit from antipsychotic medication. What's more, we cannot yet prevent schizophrenia or offer patients drugs that don't produce side effects such as agitation, weight gain and tremors.

 

Despite these sobering realities, "The Madness Pill" is a celebration of scientific genius and a salute to the wild complexity of the brain. It is also a powerful reminder of the ordeal of serious mental illness and the ever-pressing need to find better drugs to treat it.

 

---

 

Dr. Satel is a psychiatrist, a senior fellow at the American Enterprise Institute and a lecturer at Yale University School of Medicine.” [1]

 

1. Delusion's Chemical Source. Satel, Sally.  Wall Street Journal, Eastern edition; New York, N.Y.. 29 July 2026: A13.