What causes Schizophrenia?

There is no known single cause of schizophrenia. Many diseases, such as heart disease, result from an interplay of genetic, behavioral and other factors, and this may be the case for schizophrenia as well. Scientists do not yet understand all of the factors necessary to produce schizophrenia, but all the tools of modern biomedical research are being used to search for genes, critical moments in brain development, and other factors that may lead to the illness.

Can It Be Inherited?
It has long been known that schizophrenia runs in families. People who have a close relative with schizophrenia are more likely to develop the disorder than are people who have no relatives with the illness. For example, a monozygotic (identical) twin of a person with schizophrenia has the highest risk — 40 to 50 percent — of developing the illness. A child whose parent has schizophrenia has about a 10 percent chance. By comparison, the risk of schizophrenia in the general population is about 1 percent.

Scientists are studying genetic factors in schizophrenia. It appears likely that multiple genes are involved in creating a predisposition to develop the disorder. In addition, factors such as prenatal difficulties like intrauterine starvation or viral infections, perinatal complications, and various nonspecific stressors, seem to influence the development of schizophrenia. However, it is not yet understood how the genetic predisposition is transmitted, and it cannot yet be accurately predicted whether a given person will or will not develop the disorder.

Several regions of the human genome are being investigated to identify genes that may confer susceptibility for schizophrenia. The strongest evidence to date leads to chromosomes 13 and 6 but remains unconfirmed. Identification of specific genes involved in the development of schizophrenia will provide important clues into what goes wrong in the brain to produce and sustain the illness and will guide the development of new and better treatments. To learn more about the genetic basis for schizophrenia, the NIMH has established a Schizophrenia Genetics Initiative that is gathering data from a large number of families of people with the illness.

Is It Caused by a Chemical Defect in the Brain?
Basic knowledge about brain chemistry and its link to schizophrenia is expanding rapidly. Neurotransmitters, substances that allow communication between nerve cells, have long been thought to be involved in the development of schizophrenia. It is likely, although not yet certain, that the disorder is associated with some imbalance of the complex, interrelated chemical systems of the brain, perhaps involving the neurotransmitters dopamine and glutamate. This area of research is promising.

Is It Caused by a Physical Abnormality in the Brain?
There have been dramatic advances in neuroimaging technology that permit scientists to study brain structure and function in living individuals. Many studies of people with schizophrenia have found abnormalities in brain structure (for example, enlargement of the fluid-filled cavities, called the ventricles, in the interior of the brain, and decreased size of certain brain regions) or function (for example, decreased metabolic activity in certain brain regions).

It should be emphasized that these abnormalities are quite subtle and are not characteristic of all people with schizophrenia, nor do they occur only in individuals with this illness. Microscopic studies of brain tissue after death have also shown small changes in distribution or number of brain cells in people with schizophrenia. It appears that many (but probably not all) of these changes are present before an individual becomes ill, and schizophrenia may be, in part, a disorder in development of the brain.

Developmental neurobiologists funded by the National Institute of Mental Health (NIMH) have found that schizophrenia may be a developmental disorder resulting when neurons form inappropriate connections during fetal development. These errors may lie dormant until puberty, when changes in the brain that occur normally during this critical stage of maturation interact adversely with the faulty connections. This research has spurred efforts to identify prenatal factors that may have some bearing on the apparent developmental abnormality.

In other studies, investigators using brain-imaging techniques have found evidence of early biochemical changes that may precede the onset of disease symptoms, prompting examination of the neural circuits that are most likely to be involved in producing those symptoms. Meanwhile, scientists working at the molecular level are exploring the genetic basis for abnormalities in brain development and in the neurotransmitter systems regulating brain function.