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.

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 - 40 to 50 % - 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%.

While highly heritable (some estimates are as high as 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. One recent review of the genetic evidence has suggested a 28% chance of one identical twin developing Schizophrenia if the other already has it. A study conducted about Schizophrenia in twins, carried out for persons in the Finnish Twin Cohort, involving 16,649 like-sexed twin pairs, found a concordance rate for Schizophrenia of only 11.0% among monozygotic twins, and only 1.8% among dizygotic twins.

While it is important to note the extremes (high and low) in reported concordance rates, the majority of studies do fall close to the 50% mark.

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 non-specific 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.

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.

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 National Institutes of Mental Health (NIMH) has established a Schizophrenia Genetics Initiative 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.

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 anti-psychotic 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 anti-psychotic medication (called atypical anti-psychotic medication) is equally as 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.

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 (feg: enlargement of the fluid-filled cavities, called the ventricles, in the interior of the brain, and decreased size of certain brain regions - especially prominent in a number of people showing negative symptoms) or function (for example, decreased metabolic activity in certain brain regions). It should be emphasised 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 NIMH have found that Schizophrenia may be a developmental disorder resulting when neurons form inappropriate connections during foetal 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.

Evidence for the criticality of foetal development comes from women who were pregnant during the Dutch famine of 1944, where many people were close to starvation and serious malnutrition may have impacted upon foetal development. These women have been shown to have had a higher chance of having a child who would later develop Schizophrenia.

In recent studies using brain-imaging techniques, investigators 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.

Studies using neuropsychological tests and brain scanning technologies such as fMRI and PET to examine functional differences in brain activity have shown that differences seem to most commonly occur in the frontal and temporal lobes and the hippocampus. These differences are heavily linked to the neurocognitive deficits which often occur with Schizophrenia, particularly in areas of memory, attention, problem solving, executive function and social cognition.

Is Schizophrenia caused by Stress?

There is considerable evidence indicating that stress may trigger episodes of Schizophrenia. For example, emotionally turbulent families and stressful life events 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.

One curious finding is that people diagnosed with Schizophrenia are more likely to have been born in winter or spring (at least in the northern hemisphere). However, the effect is not large and it is still not clear why this may occur.

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 pregnancy, suggesting that even psychological trauma in the mother may have an effect.

Developed initiallyfrom Wikipedia articles under the GNU Free Documentation Licence, with additional material from the National Institutes of Mental Health