Schizophrenia

Numerous twin, family, and adoption studies from around the world indicate a familial basis for schizophrenia and point to a genetic influence. The first-degree biological relatives (parents, siblings, and children) of a person with schizophrenia have about a 10 percent chance of having the diagnosis whereas the risk for second-degree relatives (uncles, aunts, cousins, and grandparents) drops by more than half. The risk to the co-twin of an identical twin with schizophrenia is about 50 percent (Gottesman 1991). Findings such as these hold even when individuals are not raised by their biological relatives and clearly indicate that the risk of having schizophrenia is a function of the degree of genetic overlap with an affected person. If schizophrenia were due only to heredity, then because identical twins share all of their genes in common, both members of a pair would be affected if one develops the disorder. When both are affected, the pair is said to be concordant. The fact that identical twins are often discordant for schizophrenia confirms the important role environmental factors play in its genesis. These findings have given rise to a diathesis-stress model positing that it is the risk for schizophrenia (the diathesis) that is inherited, not schizophrenia per se. Whether schizophrenia arises in an individual with the diathesis depends on other factors, including the nature of environmental stress encountered over the lifespan.

Various research strategies have taken advantage of the familial nature of schizophrenia risk in an effort to elucidate causal mechanisms. One approach has been to study prospectively the young children of those with schizophrenia. As adults, study participants can be divided into those who did and those who did not develop schizophrenia and can be compared on measures collected before the onset of illness. Several of these investigations, called longitudinal high-risk studies, have been launched in different countries including Denmark, Israel, Sweden, and the United States (see Erlenmeyer-Kimling 2000). Compared to children of healthy participants, children of schizophrenic parents tend to have neurological, motor, social, memory, planning, and attentional dysfunctions that precede illness and are similar to those seen in adult schizophrenia (Erlenmeyer-Kimling 2000).

No genes for schizophrenia have been found, and the genetic mechanism by which the diathesis for schizophrenia is transmitted is unknown. There is growing concern that this state of affairs will persist as long as the identification of gene carriers depends on diagnosing schizophrenia based on the self-report of symptoms. The symptoms of schizophrenia are not present in all gene carriers (as the findings of discordant identical twins illustrate). Moreover, these symptoms may not be directly reflective of the biological underpinnings of the disorder. Because biological relatives of schizophrenia patients share genes with the patient, it is possible that many of them, even though they are not symptomatic, will exhibit neurobehavioral characteristics that are manifestations of the genetic diathesis. Many such characteristics have been documented in schizophrenia families, including difficulty producing certain kinds of simple eye movements and poor performance on tasks of attention and memory (Kremen et al. 1994). These investigations, like the high-risk studies mentioned above, are producing promising results, but much remains to be done before the biological mechanisms underlying the diathesis are clearly understood.

Environmental risk factors investigated in schizophrenia can be broadly grouped into social and neurobiological factors. Early theories of schizophrenia positing social influences, such as rearing by a cold and domineering (schizophrenogenic) mother (Fromm-Reichmann 1948), have not been supported by the results of controlled scientific investigation. The evidence that stressful life events contribute to the development of schizophrenia, as opposed to being a consequence of its early manifestation, is also limited. A correlation has been observed between social class membership and schizophrenia, with schizophrenia predominating in the underclass. This observation has been used to advance the hypothesis that the stresses associated with underclass rearing contribute to the development of schizophrenia. Investigations of this hypothesis have shown that this correlation is due in part to the debilitating consequences of schizophrenia leading to social migration from the upper classes into the underclass (Gottesman 1991). Nevertheless, schizophrenia patients are disproportionately born into the underclass, an observation that may reflect the likelihood that the accomplishment of the parents of schizophrenia patients is compromised because they too carry the genetic diasthesis for schizophrenia.

Birth complications constitute a neurobiological factor associated with the risk for schizophrenia. Schizophrenia has been associated with an excess of winter births. This finding is consistent with results from other investigations suggesting that events that are more likely to occur during winter pregnancies, such as viral infections, may affect the prenatal development of schizophrenia-prone persons (Torrey et al. 1994).

Investigations of risk factors have supported neurodevelopmental theories of schizophrenia. These theories hypothesize that schizophrenia develops from deleterious events early in life that disrupt pre- and post-natal brain development. This disruption may lead to poor communication among different brain regions, dysregulation of particular neurotransmitters such as the chemical messenger dopamine, and many of the neurobehavioral deviations associated with schizophrenia (Weinberger and Lipska 1995). Investigations with identical twins who are discordant for schizophrenia have indicated that a twin with schizophrenia can have abnormalities in brain structures that are not observed to the same degree in the healthy cotwin. Because identical twins have the same genetic diathesis for schizophrenia, this finding is consistent with the hypothesis that birth complications or in-utero viruses could, in a genetically vulnerable individual, constitute environmental stressors leading to disruptions in brain development.