We were kind of dragged in this direction. I was working with a group that did a lot of psychiatric rehabilitation, such as training patients on social skills, how to manage their medication, and how to develop recreational skills. The goal of this area of psychiatric rehabilitation was to teach skills to chronic patients. What we noticed was that there were huge differences from patient to patient in how well they benefited from psychiatric rehabilitation—how well they learned the material and acquired skills. This was the early 1990s, and so one of the questions we asked was: what was it about the patients that tells us whether or not they’re likely to benefit from rehabilitation? If we have a patient and we can measure a bunch of things, what’s going to explain the differences in how easily they acquire information in their rehabilitation program? This was an effort to explain variability in success of rehabilitation.

Yes. What we found in these early studies, and what has since been replicated, is that cognitive deficits tell you an awful lot about how well patients will acquire skills and learn in rehabilitation. But the factors that seemed most likely to predict rehabilitation, namely clinical symptoms such as voices, delusions, and thought disorder, didn’t tell us much about how well patients would learn in rehabilitation. It was the cognitive deficits that explained success in rehabilitation.

Not immediately. It led to a series of modest studies in the early 1990s. Nothing earth-shattering. But that was clearly the lead-up to the interest in cognition as it relates to daily life of patients. The article itself was a literature review and commentary: a summary of four of our studies, along with 12 other studies.

The paper was referred to as a special article in that journal. The American Journal of Psychiatry was the highest visibility outlet I knew of for think pieces like this related to psychiatric illness. At that point in time, they would have one or two special articles whose titles they would list on the cover, and those were high-visibility reviews or conceptual pieces.

It represented an important shift in focus. It required a refocusing away from the psychotic symptoms, which are quite frankly a lot more dramatic, to problems in attention and memory and problem-solving, which are quite frankly not that dramatic. In other words, Hollywood doesn’t make movies about these problems. When schizophrenia is portrayed in movies, the emphasis is always on paranoia and hallucinations. To make things even trickier, the medications we have for schizophrenia work well on psychotic symptoms but don’t work well on cognitive deficits. Maybe they work a little but they’re certainly not great. So the paper was a refocusing and made the argument that the psychotic symptoms which have been the focus of our diagnosis and of our treatment, and which are more interesting to many of us, do not tell us very much about how patients will move into the community and how well they manage daily activities. The cognitive deficits, which require laboratory measurements to assess and which are not as dramatic but are very stable and quite common in schizophrenia, do tell us something about how well patients function in daily life.

The conclusions also helped to resolve one paradox: that while antipsychotic medications reduce psychotic symptoms, they have made very little difference in improving community functioning for patients with schizophrenia. And the explanation for that paradox is that drugs work on one part of the illness, the psychotic symptoms, that do not account for community functioning and the drugs do not work on another part of the illness, cognitive deficits, that do explain community functioning.

The cognitive deficits we study are measured in the laboratory. Some of the measures come from clinical neuropsychology and some come from experimental psychology. For verbal memory, for instance, we might ask people to remember lists of words. For short-term memory, we might ask people to remember a series of digits. For attention, we might ask people to press a response button whenever they see a particular target stimulus that is briefly presented on a computer screen. For speed of processing, we might use paper and pencil tests that require people to quickly connect symbols on a piece of papers.

Yes. The typical individual who has schizophrenia will have these clinical symptoms, and for the most part these symptoms will be reduced by medications. They may or may not be completely gone, but they’ll be reduced. That’s the good news. But those individuals still will have trouble getting a job; they will still have trouble handling public transportation, maintaining friendships and connections with their family, even though their symptoms no longer pose a great problem. Of course, I’m talking in generalities now. And the question was, why is that happening? The cognitive deficits are helping to explain some of those lingering problems. They’re not changing with the medications, or not very much.

It did generate some controversy. There were two kinds of reactions to the paper, from academics and also from clinicians. One reaction was, "Well, wait a minute, are you saying that psychotic symptoms aren’t important? And if these cognitive deficits are so important, how come they’re not part of the diagnosis of schizophrenia and we don’t see them prominently in our patients?" So some clinicians thought that this was minimizing what they were treating. And I have always tried to be clear that when a patient goes into the emergency room with an acute psychotic episode, you don’t call a neuropsychologist. You immediately try to reduce the clinical symptoms. That’s the first thing you do. But six weeks later when the patient is stabilized you worry about why he or she hasn’t returned to functioning in the community. The other reaction I got was from clinicians, academics, and many family members who said this focus on cognition makes perfect sense. They did not know exactly what to call it but the idea that their patient, their son, their friend has problems in attention and memory and that’s why they’re not doing well in day-to-day life, that made sense to them. On one level people responded as though it was intuitive, and others responded a little negatively. One thing about this focus on cognitive deficits, it has a good historical precedence. In the last 50 years, clearly the focus in schizophrenia was on psychotic symptoms, but if you go back 100 years to the early writers in schizophrenia, there was in fact a focus on cognitive deficits, although they were not measuring them.

There’s been considerable progress, in two forms. First, the conclusions have been replicated in many follow-up studies. Second, there has been more of an effort to develop drugs that will treat cognitive deficits in schizophrenia. The National Institute of Mental Health, NIMH, now considers the cognitive deficits in schizophrenia to be a public health problem, and they have been trying to stimulate drug development specifically to treat the cognitive deficits in schizophrenia. This is best represented by an initiative from NIMH called MATRICS. Just within the last year, the FDA has also said they are willing to approve drugs for this purpose. So there is now a very strong commitment from NIMH and the pharmaceutical industry to find drugs to improve cognition in schizophrenia. Maybe in the not-too-distant future, patients with schizophrenia will receive two drugs: one to manage psychotic symptoms and one to manage cognitive deficits. We see them as two parts of the same illness, and so they deserve separate treatments. Another thing that’s happening is that we’re trying to better understand the mechanisms by which cognition is related to community functioning and to map out the intervening steps that go from attention deficits to someone having trouble on a job or maintaining contact with family members. You can think of these intervening steps as a combination of cognitive and social capacities.

Well, to some extent, I’d just be redundant. What we’re doing is taking a very complicated disease with a very high level of disability and trying to understand a component of the disease that has not traditionally received much attention. So we’re trying to understand the disability and why these patients generally don’t do well in the community, and we’re hoping to use that information to start thinking about development of new drugs to reduce this disability and make it easier for these people to function in daily life and in the community.