Dr. Joshua A. Gordon, the new director of the National Institute of Mental Health, took office in the final year of Barack Obama’s presidency. But he has this much in common with Obama’s successor: He has little patience for incremental reforms.
A 49-year-old psychiatrist who made his reputation as a brilliant researcher of mice with mutations that mimic human mental disorders, Gordon is convinced that radical changes are needed in the treatment of illnesses like schizophrenia. In an interview in his office at the NIMH campus in Bethesda, Maryland, he lamented that while modest improvements have been made in patient care over the last few decades, we don’t know enough about the brain to “even begin to imagine what the transformative treatments of tomorrow will be like.”
Few psychiatrists would disagree that change is overdue. Take depression: Current approaches, which employ drugs like Prozac or cognitive-behavioral therapy, or a combination of the two, can relieve major symptoms in only some patients. The hope is that “precision medicine” — treatments targeted to the specific biological makeup of the patient — can do for psychiatry what scientists like Gordon’s Nobel Prize-winning mentors J. Michael Bishop and Harold E. Varmus did for cancer treatment a generation ago.
Unfortunately, as Gordon is well aware, mental illness is particularly challenging in this regard. In contrast to many types of cancer, where one genetic mutation can cause unregulated cell growth, psychiatric diseases rarely stem from any single faulty gene; instead, they are typically rooted in a complex interplay of genetic, environmental, and cultural factors.
Gordon grew up in the Washington suburb of Silver Spring, Maryland, and his career has now brought him full circle. Last September he left New York City, where he had been an associate professor of psychiatry at Columbia University Medical Center and a research psychiatrist at the New York State Psychiatric Institute, to lead the NIMH. With its annual budget of $1.5 billion, this federal agency is the world’s largest funder of psychiatric research.
As Gordon defines it, the job involves both advocating for the mental health needs of Americans and developing science to guide policymakers and clinicians. He is “very excited” by the mental health provisions included in the 21st Century Cures Act, which both houses of Congress approved by overwhelming majorities late last year. The law allocates $1.5 billion in funding over the next 10 years for Obama’s BRAIN Initiative, in which researchers at the institute play a key role. (The acronym stands for Brain Research through Advancing Innovative Neurotechnologies.) It also strengthens enforcement of the Obamacare requirement that health insurance cover treatment for mental illness.
Of course, Gordon concedes that funding prospects are uncertain at best. In March, in a budget blueprint that offered few specifics, President Trump proposed cutting funding across all branches of the National Institutes of Health by about $6 billion a year, or 18 percent. But a few weeks later, Congress pushed back and actually raised NIH funding by $2 billion, which included a $110 million supplement to Obama’s BRAIN initiative, for this year.
Despite the longstanding support for mental health research from legislators on both sides of the aisle, in mid-May the president proposed trimming NIMH’s 2018 budget by more than $300 million, though again he offered few details. (Gordon wouldn’t comment on the proposal.)
In his doctoral dissertation at the University of California, San Francisco, Gordon pioneered the use of sophisticated genetic manipulations in mice to learn about the plasticity of the visual cortex.
In his lab at Columbia, he conducted numerous mouse studies on neural activity, with important implications for such psychiatric diseases as schizophrenia, anxiety, and depression. In a seminal paper published in Nature in 2010, he demonstrated how a genetic mutation on chromosome 22, which is known to boost the risk of schizophrenia 30-fold, damages the connection between key parts of the brain. As Thomas R. Insel, Gordon’s predecessor at NIMH, observed that spring, “For the first time, we have a powerful animal model that shows us how genetics affects brain circuitry, at the level of single neurons, to produce a learning and memory deficit linked to schizophrenia.”
Like Insel, Gordon plans to emphasize basic research on brain biology. That’s why he wants to continue the work launched several years ago by Insel on the Research Domain Criteria, known as RDoC, the controversial new framework for studying psychiatric disease. In contrast to the DSM, psychiatry’s longstanding diagnostic bible, which identifies broad disease categories such as depression or schizophrenia, RDoC breaks down behavior into small component parts such as apathy. While the DSM has been successful in allowing clinicians to communicate with each other, Gordon says, “as a method by which we try to understand the neurobiologic basis of disease, [it] has failed miserably.” As he notes, RDoC is not designed to replace the DSM. Its promise is that it offers researchers a useful tool to link behavior with brain function.
RDoC is still a work in progress, and Gordon proposes tweaking it. It “was built in much the same way the DSM was built,” he says, “which is to get a bunch of experts in the room and ask, ‘How is behavior organized?’ We really should have more of a data-driven approach.” To come up with the basic building blocks of behavior, he believes that researchers should instead conduct a large battery of behavioral tests on hundreds of individuals, if not thousands.
Gordon argues that such a big-data approach could be useful across his agency’s entire portfolio of research. He cites the Human Connectome Project, a multi-campus research effort modeled on the Human Genome Project. The mental health institute originated the idea, saw it through, and now stores the data. Derived from brain scans collected on 1,200 healthy individuals, the project, completed in 2015, provides a basic map of the brain and the neural connections between various brain regions. When you do this type of testing for that many people “you get tremendous statistical power and confidence in your results,” Gordon says. “We have a basic map of the brain and how it’s connected that other researchers can tap into. They can compare their datasets to it, and they can go looking in that data, because it’s publicly available, for information about how the brain functions and how it’s structured.”
And these follow-up studies have already begun. The Austen Riggs Center, a residential treatment facility in Stockbridge, Massachusetts, is now mapping the brains of a sample of its patients, who suffer from complicated psychiatric disorders. “We want to compare their characteristics to those of the normal subjects in the Human Connectome Project,” says Andrew J. Gerber, the medical director of Austen Riggs. “We hope to identify a brain region that might be amenable to change by a particular intervention — say, a new medication or type of psychotherapy.” Even though he specializes in long-term psychotherapy, Gerber is a big supporter of Gordon. “Josh focuses on neurobiology, but he also did clinical work at Columbia and his vision represents a deep integration of all perspectives,” he adds.
Gordon says he chose to do his residency at Columbia because he wanted to ensure he “got a rigorous clinical education.”
“My experiences with patients have had a big impact on me,” he adds. He was deeply affected by the fierce independence of a rail-thin middle-aged woman with schizophrenia, whom he treated in an inpatient unit during his first psych rotation at UCSF.
“Her teeth were all falling out, and she could barely put three words together,” he says. “After I put her on antipsychotic medication, she began speaking, and the first thing she said was, ‘I am not staying here.’ It made me realize that there is a person underneath this devastating illness.”
While Gordon was a popular choice among psychiatrists to lead NIMH, he does have his share of critics. Their main concern has less to do with him personally than with the overall direction of his agency over the last two decades.
Founded in 1949, the National Institute of Mental Health used to take a much more hands-on approach to treatment. In the early 1960s, when the federal government decided to deinstitutionalize many patients locked up in state psychiatric hospitals, the agency worked closely with community mental health centers to devise clinical care for the chronically mentally ill. But in the early 1990s, its role changed when the newly established Substance Abuse and Mental Health Services Administration began overseeing the delivery of services to psychiatric patients. Ever since the 1990s, which it designated “the decade of the brain,” the mental health institute has focused primarily on basic research.
The psychiatrist E. Fuller Torrey, founder of the Treatment Advocacy Center, a nonprofit based in Arlington, Virginia, that supports patients with illnesses like schizophrenia, argues that NIMH has strayed too far from its original mission. Torrey is impressed by Gordon’s qualifications, but he worries that he will not sponsor enough research on serious mental illnesses. “The share of the institute’s funding devoted to serious mental illnesses has gone down steadily over the last 20 years,” he says.
“The families of patients are upset that what it has done has not led to any new drugs or treatments,” he added.
Allen J. Frances, a former chair of the department of psychiatry at Duke University School of Medicine, who headed the task force behind DSM-IV, worries about the plight of America’s chronically mentally ill — particularly the 350,000 who are in prison and the 200,000 who are homeless. “The rest of the world doesn’t criminalize the mentally ill,” says Frances. “This is a crisis. Brain research is wonderful, but the agenda of the National Institute of Mental Health is unbalanced. And none of its research efforts over the past 25 years have helped a single patient.”
Richard A. Friedman, a professor of psychiatry at Weill Cornell Medical College in New York City, who specializes in psychopharmacology, agrees that the mental health institute’s decades of brain research have yielded few tangible results. Friedman, who is also a contributing op-ed writer for The New York Times, faults the institute for spending only 10 percent of its research funding on clinical trials research — and just half of that on psychotherapy clinical trials. “Looking at the basic mechanism of disease is useful, but we can’t wait for complete knowledge to explain all of human behavior,” he says. “Psychiatry as a whole has been neglecting the benefits of both psychotherapy and self-understanding.” Friedman argues that Gordon should fund more studies designed to help patients now coping with such common disorders as depression or anxiety.
When asked to respond to these critics, Gordon defended the institute’s priorities. “NIMH spends, on clinic trials, the same percentage as the rest of the NIH,” he says. “And you could argue that we should be spending less because we know less about the brain.
“We actually are spending a significant amount of money on clinical trials and other kinds of research that have impact on patients.”
Gordon acknowledges that psychiatry has not come up with any significant new treatments since the advent of the selective serotonin reuptake inhibitors (antidepressants such as Prozac) and the second-generation antipsychotics (such as Seroquel) decades ago. That’s precisely why he thinks the institute should continue to invest so heavily in basic science. “Our first priority is to find novel targets in the brain so that we come up with transformative treatments,” Gordon says. He suggests a new medication that directly addresses a flaw in neural connectivity, for example and says he wishes more drug companies were still involved in this kind of work.
Gordon is not interested in funding studies that do not aim high. “Some people want to take a treatment that we know works and test it in a different population or tweak it slightly, but we do not to want to make modest changes; we want to do things that matter.”
Despite his emphasis on the long game, Gordon’s research portfolio does include some initiatives that can help contemporary Americans. “The reason to focus on suicide is that modest improvements can make big differences,” he says. Out of the 44,000 Americans who committed suicide in 2015, “virtually all of them [had] been to a primary care doctor in the last 12 months.” Gordon explains that there are evidence-based methods to screen for high-risk individuals, which can get them into psychiatric care. And once these individuals have been identified, Gordon says, researchers can look at what types of treatments will actually keep them alive.
Gordon also wants to increase access to an evidence-based treatment approach called coordinated specialty care, developed by the NIMH psychologist Robert A. Heinssen, that helps patients between the ages of 15 and 25 after a first episode of psychosis. By providing an array of clinical services, including assertive case management, individual or group psychotherapy, and medication, this intervention is designed to prevent the onset of chronic mental illness.
Though Gordon hopes to revolutionize psychiatric care, he is still a strong advocate for today’s standard treatments, such as antidepressants, antipsychotics, and psychotherapy. “We know that they work — only modestly, but they do work,” he says, but adds: “These do make huge differences and improve patients’ lives. But they don’t improve them enough in many patients, and unfortunately, there are many patients who don’t get that improvement. And this is the problem that fuels my desire for transformative treatments.”