NIMH FACTS: CAUSE OF SCHIZOPHRENIA UNKNOWN


Here's the current (Saturday, February 20, 1999) "What causes schizophrenia" section of
NIMH's online schizophrenia publication says. Note the use of words such as "may,"
"perhaps," "possible," etc. which basically say that no one really knows what causes
schizophrenia, despite many, many millions of dollars being invested in this "decade of
the brain" to try and find some biological cause. 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. IS SCHIZOPHRENIA 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, A 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 (see website at
http://www-grb.nimh.nih.gov/gi.html) that is gathering data from a large number of
families of people with the illness. IS SCHIZOPHRENIA ASSOCIATED WITH 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 SCHIZOPHRENIA 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. Scientists working at the molecular level, meanwhile, are exploring the
genetic basis for abnormalities in brain development and in the neurotransmitter
systems regulating brain function.