Joshua Gordon was a first year M.D.- Ph.D. student at the University of California in San Francisco bent on a career in cancer biology when he heard a talk describing how electrically stimulating cells in a key area of the brains of monkeys could alter the animals’ perception of which direction dots were moving on a computer screen. The power of that manipulation—and the vast possibilities for probing the brain that it suggested—captivated Gordon. He was hooked. He switched his Ph.D. focus to neuroscience.
A quarter-century later, Gordon, 49, has just become director of the $1.55 billion National Institute of Mental Health (NIMH). He assumed the post last month after 19 years at Columbia University, where he completed a psychiatry residency and later joined the faculty.
For much of that time, he explored neural circuits in mice with mutations relevant to schizophrenia, anxiety disorders, and depression, trying to get at how particular mutations lead to corresponding, abnormal behaviors. In recent years, Gordon also oversaw the research projects of Columbia’s psychiatrists-in-training. And beginning in 2001, he maintained a private psychiatry practice 1 night a week, treating patients with depression, anxiety, and, occasionally, bipolar disorder. They saw him for months or years. Closing that practice to move to the NIMH last month was, he says, “very painful.”
Just weeks into his new job, Gordon was challenged by two former colleagues in a pair of prominent op-eds. The clinical psychiatrists charged that under Gordon’s predecessor, Thomas Insel, NIMH—the largest mental health research funder in the world—has swung too far toward basic neuroscience, neglecting research on the issues that touch patients every day. Gordon needs to change that, they asserted.
Science sat down with Gordon last week in his NIMH office to discuss his reaction and other matters. His responses have been edited for brevity and clarity.
Q: How has working in a lab informed your outlook as you take the reins at NIMH? And how has seeing patients done the same thing?
A: The lab has informed it in many ways, [including] the science that I know, which is around neural circuits and their relationship to psychiatric disease. I can pretty easily see the value of trying to understand how patterns of brain activity and the structure of the brain influence behavior.
Perhaps the most profound influence from the clinical side is that virtually no patient I see fits into a neat category [from the Diagnostic and Statistical Manual of Mental Disorders (DSM).] And I don’t just mean the 30 to 40 patients that I had in my practice. I mean all the patients I have ever seen.
In addition, [from 2008] I directed the research programs for the residency at Columbia. I would follow the residents, make sure they got what they needed and were progressing well. And we had residents doing research in all these other domains: clinical research, services research, policy. So through them I’m at least familiar with what it’s like to be a scientist in those areas.
Q: What are your priorities for the institute as you come in?
A: One area that I consider a priority is neural circuits. Another is computational psychiatry. I think bringing more computational formalism to psychiatric research at all levels—basic, clinical, and perhaps even implementation research—will help us do our job better.
Third, suicide is a huge clinical problem. It’s a cross-diagnostic problem and it’s one for which we have evidence bases for at least short-term treatment and prevention.
Q: How and why would you prioritize neural circuit work at NIMH?
A: Advances in technology have led to increasingly powerful tools that enable neuroscientists to measure and influence neural activity in specific neural circuits. Using these tools, we can, for instance, reduce depressionlike behavior in mouse models. It is tantalizing to imagine adapting these tools for use in humans.
We don’t yet know whether these techniques would be therapeutically useful. But unless we start laying the groundwork now, we won’t be able to find out in the future. We can begin by developing the necessary tools and approaches. To some extent, the BRAIN [Brain Research through Advancing Innovative Neurotechnologies] Initiative is engaged in just this. But specific investments in NIMH areas of interest, such as developing approaches to identify and influence circuits related to mood and cognition in animal models that can bridge between mice and humans, will also be crucial.
Q: Recently, The Washington Post and The New York Times published commentaries from clinical psychiatrists who were critical of the recent emphasis on basic neuroscience at NIMH. One accused your predecessor of “strangling [NIMH’s] clinical research budget.” Another argued that NIMH “has lost sight of its most fundamental mission: finding ways to ease the burden of mental illness for those affected by it today.” The second op-ed noted that since 2012, “a full 85 percent of non-AIDS-related grant funding has been channeled to basic scientific research,” shortchanging research on existing treatments and services. Will you change that balance?
A: That [corresponding] 15% number doesn’t count a lot of the [$390 million in] translational-clinical stuff we’re doing as being clinical research. But that’s not fundamental. They are arguing that the balance is off. And I think that’s an argument we have to pay attention to. [But] I don’t think it’s my duty to respond to these articles. Because I am trying to figure out the field as a whole, to listen to others in the field on all sides, and then make a decision about funding.
In terms of the balance, I think my first priority is good science. Where there are opportunities in psychiatry for short-term effects, we are going to try to take advantage of them. Absolutely. We’d be mad not to. We know so little about the brain, we have so few truly novel treatments in the pipeline that I’m all ears. But I’m not hearing a lot of people say to me: “We have these short-term gains that we can make in this area and that area.”
Q: Insel directed NIMH for 13 years. How will your directorship chart a different course, or will it?
A: I don’t know the answer to that yet. … Many of the things [Insel] has done I really think are wonderful. But I know that several of the things he has done are very controversial in the community. That includes [the] RDoC [Research Domain Criteria].
Q: The RDoC project aims to incorporate genetics, imaging, cognitive science, and other quantifiable information to underpin a new psychiatric disease classification system. Is the implication that the DSM’s classification of disease by symptoms should be dispensed with? Is it a 20th century artifact?
A: I’m not sure Tom [Insel] would agree with that last statement. But I certainly disagree. I think [the] DSM is incredibly useful. Doctors talk in terms of diagnoses.
Maybe [the] RDoC is going to be very helpful and we are going to be able to say: “You have [this or that degree of] a deficit in the negative affect domain in fear expression.” But it may also be useful to say: “And it is panic disorder,” or, “It is [an] anxiety disorder.” It may be mathematically that combining those two things [the RDoC assessment and the DSM assessment] gives you more information. And one of the reasons is that it tells you what the clinician sees.
I am a strong supporter of the basic idea of breaking down behavior in parts and [the] RDoC is seemingly one way to do it. If we are going to make transformative progress for our patients, for individuals who are suffering, we need to get to the neurobiology. And so [the] DSM is in my mind not enough.
Q: What is the payline for investigator-initiated [R01] grants at NIMH?
A: It’s between the 10th and 20th percentiles. Almost without exception the top 10% of grants are getting funded. Within that 10th to 20th percentile we do a lot of—and this is actually a controversial thing—evaluating our portfolio, deciding on a grant almost but not quite on a case-by-case basis. Deciding, No. 1, whether that [grant proposal] is really within the heart of NIMH’s mission and, No. 2, whether it might duplicate things that we are already doing.
Q: So in effect you are saying those in the 10th to 20th percentile are all worthy of funding?
A: As a scientist I can tell you that there are grants well above the 20th percentile that are absolutely worthy. And that’s why we do that with the 10th to 20th percentile grants. Because we can’t fund to 20. Not now, anyway. And yet they are all worthy.
Q: Insel was NIMH director for 13 years. How long do you foresee staying in the job?
A: As long as I think that I am making progress and I enjoy it.