What causes it?
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 has it.
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 an effect.
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 treatments.
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.
