Feature

The American Psychological Foundation (APF) recently awarded its first Alexander Gralnick Research Investigator Award to Philip S. Holzman, PhD, in recognition of his distinguished and innovative research career.

APF will award the $20,000 prize biennially for exceptional research contributions and mentoring accomplishments in the area of schizophrenia and other serious mental illnesses.

The fund supporting the award honors the late Alexander Gralnick, MD, and reflects the breadth of his accomplishments and contributions to the field of serious mental illness.

After serving in World War II, Holzman trained in clinical psychology at the Menninger Foundation while receiving his doctoral degree in psychology from the University of Kansas. His early research was on perceptual and cognitive consistencies. In 1968, he became professor at the University of Chicago, and, in 1977, he accepted a professorship at Harvard University, where, in 1984, he was named the Esther and Sidney R. Rabb Professor. At Harvard, Holzman focused on schizophrenia as a brain disorder and initiated the first modern studies of the ocular motor system in schizophrenia.

He demonstrated that the eye-movement abnormality that he had discovered was genetically transmitted and could serve as a powerful phenotypic marker for molecular genetic studies. His other systematic studies are in the areas of working memory and thought disorders. He introduced the now widely adopted strategy of studying unaffected relatives to examine schizophrenia.

Q: What initially drew you to research on schizophrenia and what keeps you interested in this area of inquiry?

A: My first serious encounter with schizophrenic illness was in 1947, when, as an intern at the Menninger Clinic in Topeka, I was assigned to spend three months at the Topeka State Hospital, which was, like most state hospitals at that time, stark, smelly and dank, with no rational treatment for chronically psychotic patients. I spent much of my time talking with the patients, trying to engage them by finding out about their lives before their illness. I was struck by a bewildering discrepancy between their ability to tell me about their lives--they were mostly farmers--and their work, on the one hand, and the strangeness of their speech, on the other. Although they could tell me factual things about their lives, their language was peppered with new, idiosyncratic word coinages, peculiar misusages of phrases and illogical connection between ideas.

This discrepancy intrigued me. I wondered how their memories of their past life could be accurate (I did verify their stories) and how their thoughts, conveyed by their language usage, could be so impaired.

Q: Which areas of schizophrenia research are showing promise and which seem underdeveloped to you?

A: Today the search for brain loci of behavioral aspects of schizophrenia (and of the other psychotic conditions) seems to me to be a most valuable and productive research direction. In the past, many psychologists belittled this biological direction as a methodological error, which they disparagingly termed "reductionism." I believe that the search for the biological roots of the thought disorders that first intrigued me about schizophrenia--the unquestionable impairments in short-term ("working") memory, the dysfunctions in eye tracking that are characteristic of schizophrenic patients and a large number of their unaffected relatives--demand a relentless dissection into their simplest components, which, in turn, may involve brain physiology.

In this activity, however, many investigators have become fascinated by the new and spectacular imaging techniques, such as functional magnetic resonance imaging and positron emission tomography. They have leaped to embrace these techniques while simultaneously failing to develop the appropriate psychological paradigms that could elicit the phenomena under study. In this new era of neuroscience exploration, I believe that one should be cautious about taking "off-the-shelf" existing tests and measures for use in imaging studies. Rather, one should strive to tailor the behavioral techniques to the behaviors one is trying to study.

Q: What qualities do you try to instill in the young researchers whom you have influenced through the years?

A: There are several qualities that, on reflection, seem to be implicit, yet prominent, in our laboratory. I assume as a given that the young researcher must be absorbed, perhaps obsessively engrossed, in the subject of the investigation. Instilling in the young scientist respect for the data is a primary quality that one must teach by example. To paraphrase Polonius's advice (with apologies), "to thine own data be true." One must go where the data lead you.

A second quality is persistence. Research is exciting, but there can be long periods of routine activity when little happens that is new, and it is then that one must keep striving and call upon one's patience. Another quality is to adhere to the warning "never fall in love with one's hypothesis." Such loyalty to one's ideas can blind the scientist to their flaws and errors. It is better to be a perennial skeptic of one's own work--to be the first, not the second, to say that this or that idea of mine was incorrect.

Another maxim in our laboratory is "always pay attention to the discrepancies in the data." Do not be content only with mean values; there is a need to find the solution to the problem of the exception, the one case that doesn't follow the general trend in the data--the mystery of the outlier. Every discrepancy in the data should be explored. The variations are as important as the major theme, and, as Beethoven showed in his Diabelli Variations, the variations can be the major attraction, whereas the theme from which they sprang can be rather trite.

Q: Where do you see your own research heading over the next few years, and how specifically will the Gralnick Award assist you?

A: The research in my laboratory faces in two directions. The first stems from our conviction that schizophrenia is broader than the psychotic phenomena and includes many behaviors that occur in unaffected relatives of the patients. These include eye-tracking dysfunctions, formal thought disorder, working memory impairments and cranio-facial dysmorphic features. We intend to continue the study of each of these behaviors.

The second direction will continue our search for the genetic roots of schizophrenia. In this research program, we continue the analysis of DNA from a Danish sample of large families and from smaller families in an American sample. The money from the Gralnick goes, with gratitude to the American Psychological Foundation, to the laboratory to support both of these tracks of research.

Theodore Baroody is assistant director of the American Psychological Foundation.