Schizophrenia Research History

Schizophrenia

Changes in methods used to study a problem evolve as questions change. As answers to questions are found, new issues and new questions arise, which may require new methodologies. Therefore, the methods used in a research area change as original questions are answered and new questions are formulated.

An example is the historical sequence of the study of genetic influences on schizophrenia (Gottesman, 1991). One of the initial questions asked whether genetic factors contribute to schizophrenia. Subsequent clinical observations suggested that schizophrenia runs in families, but the observations were informal and less than systematic. In time, more precisely controlled research was carried out that verified the initial clinical observations. Verification was accomplished through differential research in which the rates of schizophrenia were measured in samples of families of patients with schizophrenia and control families. But, as you may have recognized, a major confounding variable (environmental influences) was uncontrolled in the studies. That is, the higher frequency of schizophrenia in the families of patients with schizophrenia might have been caused by either genetic influences or environmental conditions. Research methods were needed to separate the influences of genetics and environment. One of the ways developed was to study patients who had been adopted as infants and who later developed schizophrenia. The patients had a set of relatives who shared their genetic heritage (their biological relatives) and a set of relatives who shared their environment (their adoptive relatives). The rates of schizophrenia in each of these sets of relatives indicated the contributions of genetics and environment to the development of schizophrenia. The studies showed that schizophrenia is more likely in the biological relatives than in the adoptive relatives of patients with schizophrenia who had been adopted at birth. Data from such studies answered the initial question and made it clear that genetics plays an important role in the development of schizophrenia.

With that question answered, new questions were raised. For example, if genetics plays a role, what role is it and what is the role of other factors in the eventual development of the disorder? The new question was addressed by looking back into the developmental histories of schizophrenics for clues. But this is an ex post facto approach to research, and it does not allow us to test causal hypotheses. A better method was needed. Because it was known that genetics strongly influenced schizophrenia, Mednick and Schulsinger (1968) suggested studying individuals who are genetically related to schizophrenics—the offspring of mothers with schizophrenia. The approach was called “high-risk research” because the subjects identified for study had a much higher risk of developing schizophrenia than did an unselected sample. However, 95% of all patients with schizophrenia do not have a parent with schizophrenia. Therefore, this research approach produced a biased sample of patients with schizophrenia. A behavioral high-risk approach was proposed (Chapman, Chapman, Raulin, & Edell, 1978), which identified people at risk for schizophrenia on the basis of personality characteristics. The current functioning of these subjects could be studied (e.g., Levin & Raulin, 1991; Silverstein, Raulin, Pristach, & Pomerantz, 1992), and the subjects could be followed over time to determine their risk for schizophrenia and other disorders (Chapman, Chapman, Kwapil, Eckblad, Zinser, 1994; Kwapil, Raulin, & Midthun, 2000).

With the genetic risk factor established for schizophrenia, researchers began to look for the mechanisms responsible for the disorder. Careful measurement of performance known to be related to specific brain functioning gave us insight into the underlying neurological mechanism for schizophrenia (Gupta et al., 1995; Sanders, Keshanavan, & Schooler, 1994). CAT scans and MRIs allowed researchers to look at the structure of the brain of patients with schizophrenia and compare it with the structure of brains of controls (e.g., DeLisi et al. 1997; Lewine, Gulley, Risch, Jewart, & Houpt, 1990). PET scans (e.g., Buchsbaum, 1990; Stevens, 1997), rCBF records (e.g., Wood & Flowers, 1990), and EEGs (e.g., Gattaz et al., 1992; Josiassen, Roemer, Johnson, & Shagass, 1990) allowed researchers to look at the functioning of a schizophrenic patient’s brain. Computer models of brain functioning have built in various hypothesized schizophrenic brain dysfunctions to see if the models would create the symptoms seen in patients with schizophrenia (Cohen & Servan-Schreiber, 1992). Careful study of key subjects (e.g., identical twins—one of whom has schizophrenia while the other does not) has has helped to identify environmental factors contributing to the disorder (Cantor-Graae et al., 1994; Torrey et al., 1994). The nature of the risk factors has been probed with mathematical procedures developed for that specific purpose by Meehl and his colleagues (e.g., Meehl, 1995; Meehl & Yonce, 1994; Waller & Meehl, 1998). Several investigators (Korfine & Lenzenweger, 1995; Lowrie & Raulin, 1995), using these techniques, have found evidence for a taxonic category of risk—that is, for a risk factor that is all or nothing. The information gained from all these lines of research and a dozen other research approaches has fueled a renewed attack on this devastating emotional disorder.

The example illustrates how questions help shape research designs. Studies designed to answer one question often raise other questions in the process. The new questions sometimes require new research approaches, which often are created by scientists as a by-product of a “need to find the answer." We cannot predict what the next major research approach in the study of schizophrenia will be. It will be selected and/or created as the need develops, and the need to do so will be shaped by answers to current questions. But the principles behind any new research approach in this area will be the same ones underlying the designs discussed in the current text.

References

Buchsbaum, M. S. (1990). The frontal lobes, basal ganglia, and temporal lobes as sites for schizophrenia. Schizophrenia Bulletin, 16, 379–389.

Cantor-Graae, E., McNeil, T. F., Torrey, E. F., Quinn, P., Bowler, A., Sjöström, K., & Rawlings, R. (1994). Are neurological abnormalities in well discordant monozygotic co-twins of schizophrenic subjects the result of perinatal trauma? American Journal of Psychiatry, 151, 1194–1199.

Chapman, L. J., Chapman, J. P., Kwapil, T. R., Eckblad, M., & Zinser, M. C. (1994). Putatively psychosis-prone subjects 10 years later. Journal of Abnormal Psychology, 103, 171–183.

Chapman, L. J., Chapman, J. P., Raulin, M. L., & Edell, W. S. (1978). Schizotypy and thought disorder as a high risk approach to schizophrenia. In G. Serban (Ed.), Cognitive defects in the development of mental illness (pp. 351–360). New York: Brunner-Mazel.

Cohen, J. D., & Servan-Schreiber, D. (1992). Context, cortex, and dopamine: A connectionist approach to behavior and biology in schizophrenia. Psychological Review, 99, 34–77.

DeLisi, L. E., Sakuma, M., Kushner, M., Finer, D. L., Hoff, A. L., & Crow, T. J. (1997). Anomalous cerebral asymmetry and language processing in schizophrenia. Schizophrenia Bulletin, 23, 255-271.

Gattaz, W. F., Mayer, S., Zielger, P. Platz, M., et al. (1992). Hypofrontality on topographic EEG in schizophrenia: Correlations with neuropsychological and psychopathological parameters. European Archives of Psychiatry and Clinical Neuroscience, 241, 328–332.

Gottesman, I.I. (1991). Schizophrenia genesis: The origins of madness. New York: W. H. Freeman.

Gupta, S., Andreasen, N. C., Arndt, S., Flaum, M., Schultz, S. K., Hubbard, W. C., & Smith, M. (1995). Neurological soft signs in neuroleptic-naive and neuroleptic-treated schizophrenic patients and in normal comparison subjects. American Journal of Psychiatry, 152, 191–196.

Josiassen, R. C., Roemer, R. A., Johnson, M. M., & Shagass, C. (1990). Are gender differences in schizophrenia reflected in brain event-related potentials. Schizophrenia Bulletin, 16, 229–246.

Korfine, L., & Lenzenweger, M. F. (1995). The taxonicity of schizotypy: A replication. Journal of Abnormal Psychology, 104, 26-31.

Kwapil, T. R., Raulin, M. L., & Midthun, J. C. (2000). A ten-year longitudinal study of intense ambivalence as a predictor of risk for psychopathology. Journal of Nervous and Mental Disease, 188, 402-408.

Levin, R., & Raulin, M. L. (1991). Preliminary evidence for the proposed relationship between frequent nightmares and schizotypal symptomatology. Journal of Personality Disorders, 3, 8–14.

Lewine, R. R. J., Gulley, L. R., Risch, S. C., Jewart, R., & Houpt, J. L. (1990). Sexual dimorphism, brain morphology, and schizophrenia. Schizophrenia Bulletin, 16, 195–203.

Lowrie, G., & Raulin, M. L. (1995, April). Schizotypy: Taxonic or Dimensional? Paper presented at the Annual Convention of the Eastern Psychological Association, Boston.

Mednick, S. A., & Schulsinger, F. (1968). Some powerful characteristics related to breakdown in children with schizophrenic mothers. In D. Rosenthal & S. S. Kety (Eds.), The transmission of schizophrenia (pp. 267–291). Oxford: Pergamon.

Meehl, P. E. (1995). Bootstraps taxometrics: Solving the classification problem in psychopathology. American Psychologist, 50, 266–275.

Meehl, P. E., & Yonce, L. J. (1994). Taxometric analysis: I. Detecting taxonicity with two quantitative indicators using means above and below a sliding cut (MAMBAC procedure). Psychological Reports, 74, 1059–1274.

Sanders, R. D., Keshavan, M. S., Schooler, N. R. (1994). Neurological examination abnormalities in neuroleptic-naive patients with first-break schizophrenia: Preliminary results. American Journal of Psychiatry, 151, 1231–1233.

Silverstein, S. M., Raulin, M. L., Pristach, E. A., & Pomerantz, J. R. (1992). Perceptual organization and schizotypy. Journal of Abnormal Psychology, 101, 265–270.

Stevens, J. R. (1997). Anatomy of schizophrenia revisited. Schizophrenia Bulletin, 23, 373-383.

Torrey, E. F., Taylor, E. H., Bracha, H. S., Bowler, A. E., McNeil, T. F., Rawlings, R. R., Quinn, P. O., Bigelow, L. B., Rickler, K., Sjöström, K., Higgins, E. S., & Gottesman, I. I. (1994). Prenatal origin of schizophrenia in a subgroup of discordant monozygotic twins. Schizophrenia Bulletin, 20, 423–432.

Waller, N. G., & Meehl, P. E. (1998). Multivariate taxometric procedures: Distinguishing types from continua. Thousand Oaks, CA: Sage.

Wood, F. B., & Flowers, D. L. (1990). Hypofrontal vs. hypo-sylvian blood flow in schizophrenia. Schizophrenia Bulletin, 16, 413–424.