Gottesman and Shields: Understanding Schizophrenia

In 1972 Gottesman and Shields set out to gather existing evidence about schizophrenia in order to offer up a the most accurate information that was currently known about the condition and specifically the genetic transmission of the schizophrenia.

Before we get in to the detail, the studies that Gottesman and Shields reviewed in order to draw their conclusions were:

  • 3 adoption studies by Kety, Wender and Rosenthal
  • 5 twin studies by Kringlen et al. and Gottesman and Shields

In this climate of uncertainty, behavioral geneticists Irving I. Gottesman and James Shield published a review of contemporaneous studies on schizophrenia entitled “A Critical Review of Recent Adoption, Twin, and Family Studies of Schizophrenia: Behavioral Genetics Perspectives.”

Gottesman and Shields

What is schizophrenia?

Before we look at the findings of Gottesman and Shields lets fine define the condition they were examining.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders states, “Schizophrenia is characterized by delusions, hallucinations, disorganized speech and behavior, and other symptoms that cause social or occupational dysfunction.

For a diagnosis, symptoms must have been present for six months and include at least one month of active symptoms.” The symptoms and diagnostic criteria for schizophrenia are fairly well-defined today, but they were often problematic in the 130-year history of the disease.

Of course it is likely that there have been cases of schizophrenia throughout human history, but psychologists did not identify the disease as a unique condition until the end of the nineteenth century. In 1887, German physician Emile Kraepelin proposed the term “dementia praecox” to describe a disorder characterized by the symptoms now associated with schizophrenia.

As the proposed name suggests, Kraepelin believed that he was studying a form of early-onset dementia and that, as a form of dementia, the disease invariably progressed to the death of patients after the terminal deterioration of their brain tissue.

Kraepelin’s publications attracted attention in the psychiatric community, and scientists built on his work in the ensuing decades. At the beginning of the twentieth century, Swiss psychiatrist Eugen Bleuler determined that Kraepelin’s disease did not necessarily manifest in terminal deterioration of brain tissue and that patients could improve. In 1911, he advocated that the name of the condition be changed to “schizophrenia,” which means “splitting of the mind.”

While Kraepelin and Bleuler brought schizophrenia into the consciousness of the psychiatric community and the world at large, their work left the disease with a legacy of ambiguity. Kraepelin ascribed losses of cognitive abilities and mental control to the disease but never created a list of symptoms for its diagnosis.

Bleuler proposed using the plural form “schizophrenias” to emphasize the fact that he believed that he was describing a group of diseases rather than one disease. Between 1911 and 1972 the concept of schizophrenia expanded to include numerous subtypes as well as a disease spectrum, and the diagnosis, or lack thereof, of a given patient could vary from doctor to doctor.

Is the cause genetic or environmental?

Even as psychiatrists struggled to define schizophrenia, they argued about its etiology, or the factors that caused it. Over the course of the twentieth century, expert opinion shifted the blame from genetic factors to environmental and back.

Beginning with Kraepelin, most psychiatrists who studied schizophrenia worked under the assumption that the disease had a genetic etiology. In fact, scientists in the early twentieth century often structured their studies so as to analyze the mode of inheritance of “schizophrenia genes,” with the existence of such genes being taken for granted.

They studied the families of patients with known cases of schizophrenia in an effort to determine the inheritance pattern of the disease.

In the 1940s American psychiatrist Franz Kallmann appeared to confirm the fact that schizophrenia was a genetic disorder when he published the results of his twin study. Twin studies are a powerful tool for comparing the role of genes and the environment in the etiology of a disease because twins that are raised together share nearly identical environments from conception through the end of childhood but vary in the similarity of their genetic codes.

Identical, or monozygotic, twins share 100% of their genes, but fraternal, or dizygotic, twins share an average of only 50%. If identical twins display higher rates of concordance (i.e. if one twin develops schizophrenia, the other does as well) than fraternal twins, then genes must influence the disease in question. Kallmann’s study showed an 86% concordance among identical twins.

Still, proponents of the environmental etiology of schizophrenia emerged in the 1950s to question the methodology and validity of twin studies such as Kallmann’s. They gained support for their theories in 1963 when Finnish psychiatrist Pekka Tienari published the data from his own twin study. He reported 0% concordance between identical twins.

With twin studies providing conflicting results, psychiatrists turned their attention to the adoption studies published at the end of the 1960s. In some ways, adoption studies are the inverse of twin studies. A child who is born to a parent with schizophrenia and adopted by parents without the disease shares a similar genetic background but occupies a completely different environment than a child raised by a parent with schizophrenia.

Thus, genetic similarities are held constant, but environmental factors are varied, and similarities between children who were adopted away and children who were not adopted away must be due to genetics. At the “Transmission of Schizophrenia” conference held in Puerto Rico in 1967, a group of scientists reported data from adoption studies carried out in Denmark. They found children adopted from parents with schizophrenia to exhibit higher incidences of the disease than the general population.

Why did Gottesman and Shields conduct their study?

In 1966 Gottesman and Shield published a paper in which they emphasized their belief that schizophrenia did not have either a genetic or environmental cause, but rather, they believed that genetics and the environment were both involved in the development of the disease.

Scientists who published studies that appeared to be in disagreement with one another were simply providing proof of the complexity of the disease.

In 1972 Gottesman and Shield undertook a systematic review of recently published papers on schizophrenia in the field of behavioral genetics, the study of the role that genetics and the environment play in shaping the environment of an individual.

They analyzed adoption, twin, and family studies published following the 1967 “Transmission of Schizophrenia” conference. They did not conduct their review with the intent of providing a definitive statement on the etiology of schizophrenia. Instead, they sought to provide a report on the current knowledge on schizophrenia available in their field.

What did Gottesman and Shields find and how did they impact the field?

Gottesman and Shield looked closely at the methods and results of the studies that fell in their areas of interest. They did not accept the conclusions of their peers without a thorough investigation of their own, and in fact, they refuted the conclusions that some scientists had drawn from their own studies.

Ultimately, Gottesman and Shield found that there was ample evidence in the recent studies published in their field to support their assertion that genetic factors and environmental factors were both necessary for the development of schizophrenia.

Further, they showed that published data suggested that schizophrenia is a polygenic condition rather than monogenic. A trait or disease is polygenic if it is controlled by more than one gene, while it is monogenic if it is controlled by only one gene.

They found ample evidence to support the liability-threshold model of schizophrenia inheritance, a model which they first proposed in 1967. According to this model, a child inherits the liability to develop schizophrenia from his or her parents, and if the sum of a number of genetic and environmental factors reaches a certain threshold value, then the child will develop the disease.

Perhaps most importantly, Gottesman and Shield stressed the fact that their liability-threshold model could not be clearly defined in mathematical terms but that the model’s ambiguity actual made it useful. At the time of their review, the understanding of schizophrenia in the field was too limited to make definitive statements.

Gottesman and Shield believed that continued research on schizophrenia would require scientists to embrace the uncertainty that surrounded the disease until scientists could more directly analyze its physical causes.

Today, the etiology of schizophrenia remains elusive, but the work of Gottesman and Shield helped to shape the study of this complex disease. Subsequent research focused on determining schizophrenia “endophenotypes,” or traits that could lead to the observed symptoms of schizophrenia and be more closely associated with genes.

This line of research recently enabled scientists to associate the Reelin gene with schizophrenia, and other genes continue to attract the interest of scientists in the field.

Scientific study conditions us to expect precise results, but often our level of understanding in a particular field prevents us from attaining them. In 1972 Gottesman and Shield advocated embracing the uncertainty that surrounded the study of schizophrenia.

They believed that progress in the field depended on researchers admitting that they lacked the information necessary to understand the disease fully and refocusing on their efforts on finding the missing information. Their direction continues to guide scientists today.