As a graduate student, I had the good fortune to work with Professor Philip Holzman in the Psychology Department at Harvard University. He was conducting research investigating eye-tracking abnormalities in schizophrenia, which he thought might be linked to an endophenotypic marker of schizophrenia. He was also very much interested in understanding cognitive abnormalities in schizophrenia, which are among the most prominent features of this disorder. I, too, was interested in studying schizophrenia and focusing on the hallmark symptoms of schizophrenia, including delusions, hallucinations, and formal thought disorder, seemed to be an important area of scientific inquiry. I therefore began my work with Professor Holzman as my mentor and thesis adviser. My goal was to further understand formal thought disorder in patients diagnosed with schizophrenia as well as studying these same cognitive abnormalities in the first-degree relatives of patients diagnosed with schizophrenia. Of interest, we found that both patients and their first-degree relatives tended to show formal thought disorder, with relatives evincing the same patterns of thought disorder, albeit in more attenuated form.

This finding was quite exciting and I was interested in determining whether or not there was an association between cognitive abnormalities in schizophrenia and brain structure and function. With these interests in mind, I became a post-doctoral fellow in Biological Psychiatry at Harvard Medical School with Dr. Robert W. McCarley as my mentor. During the two-year fellowship I conducted a study investigating the relationship between formal thought disorder and an event related potential known as the P300. Event related potentials are EEG activity in response to a stimulation controlled by the experimenter. The P300 is an event related potential that occurs 300 ms following the occurrence of a discrepant or novel event in the environment. It is thought to be an index of the brain's ability to detect relevant from irrelevant information in the environment. As patients with schizophrenia are known to have problems with differentiating relevant from irrelevant information in the environment, I thought it would be of interest to evaluate this event related potential in conjunction with measures of cognitive functioning such as formal thought disorder and delusions and hallucinations. These studies led to the finding that patients with schizophrenia show a decrement in the P300 that is evident in the left temporal region of the brain, a region thought to be important in language functioning. This finding has since been replicated in our own research as well as by independent laboratories.

While these findings were exciting, it was clear that event related potentials are limited in terms of spatial localization of brain regions. As I was interested in looking more closely at the brain and specific brain regions that might be implicated in schizophrenia, I jumped at the opportunity to investigate structural brain abnormalities in patients diagnosed with schizophrenia using new magnetic resonance (MR) imaging technology. Accordingly, in 1987, I applied for a Career Development Award from the National Institute of Mental Health to provide me with the time needed to develop the skills necessary to conduct MR studies of schizophrenia. I was fortunate to receive this 5-year career development award, which helped me to launch a career investigating structural brain abnormalities in schizophrenia. This work has been in close collaboration with Drs. Robert W. McCarley, Ron Kikinis, and Ferenc Jolesz.

  What would you rate as your most difficult or trying professional moment?

The most difficult and trying moments professionally were at the beginning of my research career when I sometimes found it difficult to stay optimistic amidst harsh reviews on papers, and amidst the uncertainty of not knowing whether the research idea and its implementation would lead down a rat hole or to important information about schizophrenia. In retrospect, I think this time period was particularly difficult because one hasn't had the experience yet of having papers rejected, ideas criticized, etc., and such rejection is difficult to assimilate early in one's career. What helped was having a positive and encouraging mentor who encouraged me to keep doing the work and to count my successes, not my failures.

A further difficulty which has remained throughout my career is juggling time for family and work. I made the decision early in my career that family and work would be balanced in my life and I have succeeded in keeping the two balanced, though I constantly feel that my resources are being stretched too far in order to maintain this balance.

  Which of your professional achievements brings you the most satisfaction?

I would say that one of the most satisfying professional achievements is the recognition of my work by colleagues in the field. Equally satisfying for me is the recognition I have received for mentoring the next generation of clinical researchers. I understand the importance of mentoring, particularly in the early years of one's career, and I therefore devote a tremendous amount of time and energy into inspiring and supporting the research efforts of junior faculty. I also appreciate the fact that my role as a mentor is both recognized and valued. And finally, I am particularly satisfied when I look back over the course of many years of work and I see how each new question and answer has led to new discoveries and new questions to be addressed. The quest for truth is truly the ultimate satisfaction for researchers.

  What impact might your work and research advances in your field have on the general public?

I think that when I began focusing on neuroimaging studies in schizophrenia I was aware of the fact that this was a new frontier, that there was incredible excitement at being able to address long-held speculations about brain abnormalities in schizophrenia. I was even hopeful that with this new window on the brain we would be able to discern small, subtle, but important differences between control subjects and patients diagnosed with schizophrenia. I thus was aware that the research work I was conducting with my colleagues was extremely exciting because we were using brand-new techniques and applying them to investigate a disorder that has not easily yielded answers in the past. However, I don't think that any of us thought that our early work would become so highly cited. The fact that our work has been so highly cited is a delightful bonus.

  What lessons would you draw from your work to pass on to the next generation of researchers?

I spend a great deal of time working with junior faculty who are just beginning their careers in research and I think there are several lessons that I would want to pass on. First, a young and hopeful investigator must truly answer the question of whether or not s/he wants a research career. Having a research career involves so much sacrifice early on, and the rewards are thin initially, with the need for a very long apprenticeship. Once this question is answered in the affirmative, the next important lesson is to pick your mentors well. Since so much of research is apprenticeship early on, a young and hopeful investigator needs to evaluate the credentials of a mentor. First, they need to select a person who is successful in the field, and who has a track record of supporting junior faculty. The latter can often be discerned by evaluating publications to see whether or not junior faculty are listed as first author. Finally, I would say that what is most important is that junior investigators select a problem or question to address that they are really passionately interested in knowing the answer. To "chase the money" by trying to adapt one's interests to an area that is receiving more funding at the moment is deeply unsatisfactory as it is the interest of the investigator that keeps the research alive and moving. Hence my advise would be to "follow your nose" in terms of research questions but temper that with the voice of experience, i.e., a good mentor.

  If you had the power to make a single, sweeping change in the way that scientific research is conducted and presented, what would it be?

Again, a difficult and ponderous question. I actually believe that the way that research has been conducted and supported in this country works in terms of the peer review system. It isn't perfect, and there are problems, but I don't see a better alternative.

I am, however, often disappointed by the quality of scientific presentations and I think more attention should be given to increasing the quality of presentations, particularly since a clear presentation has much more impact on researchers than one that is difficult to follow and understand. Other changes I would think important are more formalized mechanisms for training the next generation of researchers. This is done on almost a haphazard basis and I think that many very bright individuals leave scientific research before even really getting started.

  Would you like to leave any other comments about your work or share a personal side of yourself to be included in the piece?

I am married and have a 16-year-old daughter.

Martha E. Shenton, Ph.D.
Harvard Medical School, Brigham & Women’s Hospital
Departments of Psychiatry and Radiology
Brockton, MA, USA