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Feature

He put twins on the map

Irving Gottesman showed how to get at the roots of schizophrenia and other complex mental illnesses

By Deane Morrison

September 11, 2007

For the better part of 40 years, University psychologist Irving Gottesman has done battle with a wily opponent that claims victims without warning, spares others just as capriciously, and springs from a shifting variety of causes. The opponent is schizophrenia, and in Gottesman it finally met its match. The much-decorated psychologist has torn the cloak of mystery from schizophrenia and other devastating mental illnesses, as well as criminal behavior and personality, to expose the roles of genetics, environmental factors, and sheer chance in shaping the mind. Thanks in large part to him, scientists have the tools to pick apart the complex causes of mental illness and harmful behaviors, a necessary step in devising treatments and preventive measures. "He's a groundbreaker in psychology, especially psychopathology research," says psychology professor William Iacono. "He laid the basis for schizophrenia resulting from the actions of many genes."

In August Gottesman, a senior fellow in the Department of Psychology and Bernstein Professor in Adult Psychiatry, received the Gold Medal for Life Achievement in the Science of Psychology from the American Psychological Association. While revealing the hand of genetics in all kinds of traits, he has striven to shoot down the idea that genetics is destiny. "We're probabilists," he explains. "Genetics is one factor. The importance of genetics varies across traits and diseases." Born in Cleveland, Gottesman came to the University in 1956 as a graduate student on the Korean War G.I. Bill. Entranced by lectures on the biology of individual differences, he soon began a study of personality traits using identical and fraternal twins who took the Minnesota Multiphasic Personality Inventory, or MMPI. The results were eye-opening. "I found that variances in certain personality traits, as measured by the MMPI in adolescents, were under strong genetic control," Gottesman says. "The main ones were social introversion and aggressive tendencies." Gottesman's work laid the groundwork for using twins to identify the underpinnings of traits, such as the Minnesota Study of Twins Reared Apart, headed by psychology professor Thomas Bouchard. Gottesman left the University after receiving his doctorate in 1960 but returned in 1966 to found the Program in Behavioral Genetics, which combines psychology and genetics to investigate the roots of behavior. In his work with twins, Gottesman discovered a genetic link to being diagnosed alcoholic in both males and females. And, working in Denmark, he found a genetic predisposition toward the commission of felonies in both sexes. But neither result means there's a gene for those specific behaviors; instead, what some people have is really poor self-control.

"I found that variances in certain personality traits, as measured by the MMPI in adolescents, were under strong genetic control," Gottesman says. "The main ones were social introversion and aggressive tendencies."

"There are predispositions that are actually to impulsivity and lack of ability to delay gratification," Gottesman explains. "These predispositions are found on a continuum. Another such trait is authoritarianism, which is a strong drive to impose one's will on others." But it was his work with schizophrenia for which Gottesman made his most indelible mark. In the late 1960s, he and British social worker James Shields undertook an exhaustive study of twins. "It was one of the most influential twin studies in the history of psychopathology research," says Iacono. "At that time, we didn't have good interviewing techniques to identify people with schizophrenia." The resulting book, Schizophrenia and Genetics: A Twin Study Vantage Point, laid out the evidence that schizophrenia results from the actions of many genes and paved the way for others to do rigorous behavioral genetics work.

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Irving Gottesman left the University in 1980, but returned in 2001 and held a retirement party on campus. On that occasion, scientific work that stemmed from his research was presented; it is all available in a book, Behavior Genetics Principles. Other books that summarize much of his work are Schizophrenia Genesis: The Origins of Madness and Psychiatric Genetics and Genomics.

The collaboration with Shields also led to some of the most startling insights of Gottesman's career. At the beginning of their studies, "the origins of schizophrenia, and indeed virtually all forms of mental illness, were attributed to dynamic processes, typically a dysfunctional relationship with parents," says Matthew McGue, University Regents Professor of Psychology. "Unfortunately, this model did not lead to effective interventions for these devastating illnesses." But Gottesman and Shields found that, compared to fraternal twins, identical twins were more likely to share the same status with respect to schizophrenia--that is, either having the disease or not. This pointed to a major role for genetics in the development of schizophrenia and ushered in a new approach to the disease. The two researchers also challenged the notion that diseases like schizophrenia and diabetes, which manifest themselves clearly, must have a clear, simple origin such as a single gene mutation. In 1967 they proposed a model in which it is the actions of many genes together that causes schizophrenia. This model "provides the conceptual basis for essentially all current genetic epidemiological research on schizophrenia," McGue says. But Gottesman wasn't through. With Danish colleague Aksel Bertelsen, he examined identical twins in which one had schizophrenia and one didn't. In such a case, conventional wisdom held that environmental factors must be causing the disease in one twin, since identical twins are genetically the same. The researchers found, however, that the children of both affected and unaffected identical twins had the same relatively high risk for developing schizophrenia. Clearly, unaffected twins could pass a genetic risk to offspring without themselves having the disease. So what actually causes schizophrenia? Although the disease is the same in every person who has it, it is caused by different combinations of traits too subtle to detect just by looking at a person, Gottesman says. Called endophenotypes, such traits are like the borderline inability to metabolize glucose, which can be detected by a test. "[The test] can detect whether somebody who's an unaffected relative of a patient with diabetes is at risk of developing the disease too," says Gottesman. "Then you're in the business of prevention. Similarly, we'd like to know the endophenotypes for obesity, criminal behavior, and alcoholism. All these problems can be attacked by my approach, which is to look for endophenotypes that precede symptoms and the accumulation of symptoms that lead to a specific diagnosis or behavior." A focus on each person's individual patterns of endophenotypes opens the door to tailoring medical treatments to each patient and educational styles to each student, he says. What was perhaps Gottesman's finest moment came in 1972, when a debate was raging about the causes of a 15-point gap between IQ scores of black and white Americans. Minnesota senator Walter Mondale called him to testify before the U.S. Senate about the contribution of genetics to intelligence. Gottesman testified that while genes are a factor, so are economic, educational, and nutritional disparities, among others, likening an IQ test to a thermometer reading. "If, unknown to the examiner, a child had been sucking on ice cubes or drinking hot tea before testing, you would be obtaining accurate but misleading information," he said. "I would suggest to you with respect to the IQ testing of many disadvantaged children, that the readings reflect an intellectual diet of ice cubes between the time of conception and entrance to elementary school."