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The Causes of Schizophrenia


Experts now agree that schizophrenia develops as a result of interplay between biological predisposition (for example, inheriting certain genes) and the kind of environment a person is exposed to. These lines of research are converging: brain development disruption is now known to be the result of genetic predisposition and environmental stressors early in development (during pregnancy or early childhood), leading to subtle alterations in the brain that make a person susceptible to developing schizophrenia. Environmental factors later in life (during early childhood and adolescence) can either damage the brain further and thereby increase the risk of schizophrenia, or lessen the expression of genetic or neurodevelopmental defects and decrease the risk of schizophrenia. In fact experts now say that schizophrenia (and all other mental illness) is caused by a combination of biological, psychological and social factors, and this understanding of mental illness is called the bio-psycho-social model.

The Path to Schizophrenia - The diagram above shows how biological, genetic and prenatal factors are believed to create a vulnerability to schizophrenia. Additional envronmental exposures (for example, frequent or ongoing social stress and/or isolation during childhood, drug abuse, etc.) then further increase the risk or trigger the onset of psychosis and schizophrenia. Early signs of schizophrenia risk include neurocognitive impairments, social anxiety (shyness) and isolation and "odd ideas". (note: "abuse of DA drugs" referes to dopamine affecting (DA) drugs). Source: Presentation by Dr. Ira Glick,"New Schizophrenia Treatments" Read below for an indepth explanation of the genetic and environmental factors linked to schizophrenia.

Neither the biological nor the environmental (psycho-social) categories is completely determinant, and there is no specified amount of input that will ensure someone will or will not develop schizophrenia. Moreover, risk factors may be different for different individuals - while one person may develop schizophrenia due largely to a strong family history of mental illness (e.g. a high level of genetic risk), someone else with much less genetic vulnerability may also develop the disease due to a more significant combination of prepregnancy factors, pregnancy stress, other prenatal factors, social stress, family stress or environmental factors that they experience during their childhood, teen or early adult years. The exact process by which environmental factors and stress gets translated into brain changes and ultimately psychosis or schizophrenia is increasingly thought to be a result of epigenetics, and recent research suggests exactly how stress might trigger these brain changes.

Research has now shown that children's and teen's brains are very sensitive to stress (up to 5 to 10 times more sensitive than adult brains) and can be damaged by frequent or ongoing stress. What seems like mild to moderate stress for an adult, may be very severe stress for a child. This stress-related brain damage can greatly increase risk for many types of mental illness later in life. (see diagram below that provides an example of how schizophrenia might develop in a person)


The generally accepted causes or origins flowchart for schizophrenia. Source: Presentation by Dr. Ira Glick,"New Schizophrenia Treatments" - Stanford University Schizophrenia and Bipolar Education Day, July 2005 (Click to see full presentation)

This means that there is always hope, and there are many things you can do to reduce your own or your childrens' risk of developing schizophrenia. Recent scientific research on the causes of schizophrenia is increasingly suggesting that it may be possible to prevent many cases of schizophrenia through actions taken during pregnancy (before a person is born) as well as by actions throughout early childhood and later in life. Such prevention factors can be especially important for people who know they have a family history of any type of serious mental illness (depression, bipolar disorder, schizophrenia, OCD, anxiety, etc.). Follow this link to learn more about schizophrenia prevention.

How Genes Contribute to Schizophrenia:

There is no doubt a strong genetic component to schizophrenia - those who have immediate relatives with a history of this or other psychiatric diseases (for example, schizoaffective disorder, bipolar disorder, depression, etc) have a significantly increased risk for developing schizophrenia over that of the general population. However, twin studies have shown that simple genetic transmission is far from the whole story - if one identical twin has schizophrenia, the risk for the other twin (who has the exact same genes as his/her sibling) is only about 50%. This indicates a complexity of genetics and environment that is not yet well understood, rather than a case of single or multiple gene presence in the body automatically conferring a certain risk for developing schizophrenia.

For almost as long as scientists have pondered how nature and nurture shape personality, intelligence, health (or disease) and other traits, they've assumed that each contributes some percentage to the trait. Maybe intelligence is 55% genes and 45% environment. As one science author noted - it used to be thought that the nature / nurture relationship in people was kind of like succotash is 60% corn and 40% lima beans. But it is becoming increasingly clear that people are not like this - and some genes are only turned on when a person is exposed to a specific environment. Rather than nature (i.e. genes) and nurture (i.e. environment) each kicking in a fraction of the influences that nudge traits in one or another direction, new studies show the innate potential we call nature becomes reality only when exposed to a certain kind of nurture or environment. A gene contributes 0% of what you become if you don't grow up in an environment that turns it on, and environment contributes 0% if you lack the gene it acts on. But if both the gene and the environment that turns it on are present, then it's as if each contributes 100%.

An example of this, researchers have suggested, is the the gene that has been linked to shyness (social anxiety) -- the "shy gene" is called 5-HTT, and it comes in two forms. In adults, the short version has been linked to anxiety and to high activity in the brain's fear-generating amygdala. But in kids, the picture of how the nature/nurture relationship has been fuzzy. A 2005 study found that children with two copies of the short form tended to be very shy, but earlier studies found no such connection. An explanation may be at hand, suggests a recent research study. "Only children with the short form of the gene and mothers who had little social support and poor social networks, which increases social stress, were shy as 7-year-olds," stated Prof. Fox, whose study appeared in the science journal "Psychological Science". Dr, Fox continued, "We don't know the molecular mechanism by which a mother's [or father's] behavior reaches down to inhibit or elicit the expression of a gene, but clearly that's happening." There have been hints that shy toddlers stay shy if their parents are very protective. But if parents make a conscious effort to get their child to play with other kids when they are young, she is more likely to shake her "innate" introversion. After all, says Prof. Fox, a young child's brain shows an astounding ability to change in response to experience. In an earlier study, he and colleagues found that shy children in day care became less shy once they reached school age than shy kids who had spent their days only with mom.

Studies that support this new view of how nature and nurture combine to influence brain development are accumulating quickly. In 2002, scientists reported that boys with one form of the MAOA gene, long associated with aggression and criminality, had a higher-than-normal risk of growing up to be antisocial or violent only if they were also neglected or abused as children. If they had the "violence gene" but also a loving, nonabusive family, they turned out fine. The short form of the 5-HTT gene is associated with depression and suicide, but only if you experience many highly stressful life events, including growing up in emotionally cold, unsupportive homes marked by stress, conflict and anger. New research has now shown how family stress damages children's brains - see this news story.

Similarly with schizophrenia it is becoming increasingly evident that having the gene(s) associated with schizophrenia is just a starting point. If you have the genes, but don't experience the environmental contributing factors or "triggers" for schizophrenia - then evidence suggests that you'll never get schizophrenia. However, if you are exposed to certain environmental factors - then the chances seem to increase (and the more environmental factors a person experiences, the higher the risk) that the person will ultimately get schizophrenia.

An example of this theory with regard to schizophrenia is a recent research study that indicated that people who had multiple copies of a version of the COMT gene and who smoked marijuana had a 1,000% increase in their risk of developing schizophrenia. (source: Biol Psychiatry. 2005 May). This research may partly explain the increased risk of developing schizophrenia for people who smoke cannabis / marijuana.

Another recent study done in Finland indicated that adopted children that had a high genetic/biological risk of schizophrenia (their mother had schizophrenia) - had an 86% lower rate of developing schizophrenia when brought up in a healthy family vs. a dysfunctional family. In the healthy family only 6% of the children developed schizophrenia, whereas approximately 37% of the children of dysfunctional families developed schizophrenia (read full report on study here - A Healthy Family Social Environment May Reduce Schizophrenia Risk by 86% in High Risk Groups).

Some of the genetic factors that are being researched right now are multiple genes contributing to the disease (there are about a dozen genes that are leading candidates), and the possibility of epigenetic interactions (that is, certain genes and other biological molecules that determine whether and when certain genes present in the body are turned on or off) is being investigated and has gained considerable research support during the past five years.

How Environment Contributes to Schizophrenia:

First of all - its important to understand that when schizophrenia researchers talk about "environment" they have a very broad definition that basically includes everything other than "genes" or genetic factors. So, whereas the typical person might think of their "environment" as their house, or their neighborhood - scientists trying to understand the factors that influence the development of schizophrenia define environment to include everything from the social, nutritional, hormonal and chemical environment in the womb of the mother during pregnancy, up to the social dynamics and stress a person experiences, to street drug use, education, virus exposure, vitamin use, and much, much more. So, when you see the word "environment" used when talking about the causes of schizophrenia - another way to think of it is "everything other than genes". Its basically the same as when people talk about "nature vs. nuture" - what they are saying is "genes vs. environment".

The following diagram displays the increased relative risk (or "odds ratio") that is associated with some of the more well-researched environmental factors (family history/genetics is included for comparison) that have been linked with schizophrenia. In this diagram, the "odds ratio" represents the relative increase in risk associated with schizophrenia, where a "1" is average. So, a child born during the winter months (January through March/April, in the Northern hemisphere) has about a 10% higher risk of schizophrenia than average. A person born in an urban environment has about a 50% (with an odds ratio of 1.5) higher risk of developing schizophrenia. A child born from a mother who has Rubella has about a 500% increased risk of schizophrenia, etc. The "family history" odds ratio identified below is actually much more difficult to estimate than the number below suggests - it depends upon (as mentioned in the genetic factors above) the level of interelatedness of the family member who had schizophrenia, and other brain disorders in the family. To get an accurate reading on this for any individual it is best to talk with a genetic counselor.

Source: Public Library of Science, 2005 - Comparison of a Selected Set of Relatively Well-Established Risk Factors for Schizophrenia, Focusing Mainly on Pre- and Antenatal Factors (abbreviations: CNS, central nervous system; depr, depression).

Please note that some of the well-known schizophrenia risk factors identified in the above diagram have been grouped together under one or more categories below. For example, bereavement (death of a spouse or close family member), as well as flood, the unwantedness of a child (i.e. if the pregnancy was unexpected and undesired at that time), and maternal depression, can all be considered to be different types of high stress situations for the mother and child. Hypoxia (low oxygen levels at birth), and pre-eclampsia, might be grouped under the "birth complications" listed below.

Click on each hyperlinked "Risk Factor" identified below to access further scientific information about that risk factor, as well as avoidance techniques for reducing risk. (Special Thanks to Dr. Pat McGorry and his team at the University of Melbourne for reviewing and providing input on this information. Special thanks also to Dr. Tom McGlashan and Dr. Scott Woods of Yale University's PRIME center for their help)

Recent News Updates on Research into the Causes of Schizophrenia

An introduction to preventing schizophrenia - an article on the current research
























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