While the reliability of the schizophrenia diagnosis introduces difficulties
in measuring the relative effect of genes and environment (for example, symptoms
overlap to some extent with severe bipolar disorder or major depression), there
is evidence to suggest that genetic vulnerability modified by environmental
stressors can act in combination to cause schizophrenia.
A recent review listed seven genes as likely to be involved in the inheritance
of schizophrenia or the risk of developing schizophrenia. Evidence comes from
research (such as linkage studies) suggesting multiple chromosomal regions are
transmitted to people who are later diagnosed as having schizophrenia. Some
family association studies have demonstrated a relationship to a gene known
as COMT that is involved in encoding the dopamine catabolic enzyme catechol-O-methyl
transferase. This is particularly interesting because of the known link between
dopamine function, psychosis, and schizophrenia.
While highly heritable (close to 70%), schizophrenia is a disorder of complex
inheritance (analogous to diabetes or high blood pressure). Thus, several genes
interact to generate risk for schizophrenia. Genetic evidence for the role of
the environment comes from the observation that identical twins do not universally
develop schizophrenia. A recent review of the genetic evidence have suggested
a 28% chance of one identical twin developing schizophrenia if the other already
There is also considerable evidence indicating that stress may trigger episodes
of schizophrenia. For example, emotionally turbulent families8 and stressful
life events9 have been shown to be risk factors for relapses or triggers for
episodes of schizophrenia. Other factors such as poverty and discrimination
may also be involved. This may explain why minority communities have much higher
rates of schizophrenia than when members of the same ethnic groups are resident
in their home country.
One particularly stable and replicable finding has been the association between
living in an urban environment and risk of developing schizophrenia, even after
factors such as drug use, ethnic group and size of social group have been controlled
for. A recent study of 4.4 million men and women in Sweden found a 68-77% increased
risk of psychosis for people living in the most urbanised environments, a significant
proportion of which is likely to be accounted for by schizophrenia.
In addition to the risk factors listed above, researchers have curiously found
that those suffering from schizophrenia are much more likely to have been born
during the Winter months, particularly February and March. Researchers studying
manic-depressive disorder have also found that this phenomenon applies to their
patients as well.
Although no definite causes of schizophrenia have been identified, most researchers
and clinicians currently believe that schizophrenia is primarily a disorder
of the brain.
It is also thought that processes in early neurodevelopment are important,
particularly during pregnancy. For example, women who were pregnant during the
Dutch famine of 1944, where many people were close to starvation, had a higher
chance of having a child who would later develop schizophrenia10. Similarly,
studies of Finnish mothers who were pregnant when they found out that their
husbands had been killed during the Winter War of 1939 - 1940 have shown that
their children were much more likely to develop schizophrenia when compared
with mothers who were found out about their husbands' death before or after
pregnancy11, suggesting that even psychological trauma in the mother may have
In adult life, particular importance has been placed upon the function (or
malfunction) of dopamine in the mesolimbic pathway in the brain. This theory,
known as the dopamine hypothesis of schizophrenia largely resulted from the
accidental finding that a drug group which blocks dopamine function, known as
the phenothiazines, reduced psychotic symptoms. These drugs have now been developed
further and antipsychotic medication is commonly used as a first line treatment.
However, this theory is now thought to be overly simplistic as a complete explanation.
Partly as newer antipsychotic medication (called atypical antipsychotic medication)
is equally effective as older medication, but also affects serotonin function
and may have slightly less of a dopamine blocking effect. Psychiatrist David
Healy has also argued that pharmaceutical companies have promoted certain oversimplified
biological theories of mental illness to promote their own sales of biological
Much recent research has focused on differences in function in certain brain
areas in people diagnosed with schizophrenia. Studies using neuropsychological
tests and brain scanning technologies such as fMRI and PET have shown that differences
seem to most commonly occur in the frontal lobes, hippocampus, and temporal
lobes. These differences are heavily linked to the neurocognitive deficits which
often occur with schizophrenia, particularly in areas of memory, attention,
problem solving, and social cognition.
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