Throughout the years, there have been many different theories about what causes psychosis, many of which have been rejected because they were found to be incorrect.

Recently, it has become increasingly clear that many of the current theories, such as the "chemical imbalance theory", the "genetic vulnerability theory", the "complex disease theory" and the "stress & vulnerability theory" all share similar conclusions. The majority of researchers now agree that most cases of psychosis, like many other common disorders, such as heart disease, diabetes and asthma, to name a few, are caused by a combination of inherited genetic factors and external environmental factors.

The picture below shows how a person might develop psychosis as a result of a combination of genetic and environmental vulnerability factors. A full jar represents a person with psychosis.

The Research

Outlined below are a few studies that support the theory that psychosis is caused by a combination of genetic and environmental vulnerability factors.

Family Studies

It has been known for a very long time that psychosis can seem to run in families. This could easily lead people to believe that psychosis is simply inherited through genes, but when we look more closely at these situations we realize that there are several reasons why we might see psychosis running in families.

• perhaps children do indeed inherit genes that make them more vulnerable to psychosis
  
• perhaps children who have a parent with psychosis may be more vulnerable to psychosis themselves because they learn it in their home environment
  
• perhaps it is a combination of both these situations

Because of this, researchers have been trying to examine why psychosis runs in families by studying twins and adopted children.

Twin Studies

Twin studies help researchers understand how much genetics contribute and how much the environment contributes to the development of a psychosis. This is because identical twins share all of their genetic information (100% of their genes!) and non-identical twins share about half of their genetic information (50% of their genes).

If genes alone caused psychosis, we would expect that if one of the identical twins were to develop a psychosis, then the other twin would also develop the same illness 100% of the time. We would also expect that if one of the non-identical twins were to develop a psychosis, the other twin would also develop the same illness about 50% of the time.

What we found out is that, in general, if one of the identical twins has a psychosis, the other will develop the same illness about 50% of the time, and that this number is lower for non-identical twins. This suggests that genes do play a role in psychosis, but that they are certainly not the only factor contributing to psychosis!

Adoption Studies

Adoption studies are another way for researchers to try to understand how much genetics contribute and how much the environment contributes to the development of a psychosis.

There are a number of different ways to conduct an adoption study. One is to compare the histories of children of people with psychiatric problems who are adopted by unaffected families with the histories of children of unaffected parents similarly raised by unaffected families.

If genetic factors play a role, then the adopted children of people with psychiatric problems should develop the same problems more frequently than the adopted children of unaffected families. Again, in general this has been the outcome of these studies, suggesting a genetic contribution to psychiatric problems, however, adoption studies also show that genetic vulnerability factors on their own are usually not enough to cause psychosis. Environmental vulnerability factors are also needed for a person to develop a psychosis.

Genetic Vulnerability Factors

To properly understand what the genetic vulnerability factors are, we need to start at the beginning by looking at DNA, chromosomes and genes. For an exploratory tour of the world of DNA, chromosomes and genes, please click here to get a behind the scenes look at how these characters play a role in the development of psychosis. For a quick, simplified version, read below.

Our DNA contains genes, which give our bodies the instructions on how to make proteins. Proteins are the building blocks of all the different cells in our bodies, including neurotransmitters, receptors and transporters in the brain.

When there is a mistake in a gene, it is called a mutation. Mutations are common and everyone has some. Because genes contain the instructions on how to make proteins, the ones with mistakes can produce proteins that may not perform their functions as well as they should. When a mutation occurs in a gene that contains the instructions for a brain protein, like a neurotransmitter, it may contribute to a chemical imbalance in the brain, which is one of the factors in the development of psychosis.

In the last couple of years, research to find mutations in genes that might increase vulnerability to psychosis has come a long way. Researchers have found mutations in several genes, which scientists think might contribute to schizophrenia and bipolar disorder, however, each of these genes is thought to increase a persons vulnerability to psychosis by only a small proportion.

Environmental Vulnerability Factors

There are many different environmental factors that have each been shown to lead to a small increase in the likelihood of someone developing psychosis. For example, research has shown that it is two times more common for individuals with schizophrenia to have had a difficult delivery at birth. Other environmental vulnerability factors include being born in the winter months, being brought up in a big city, immigration, childhood head injury, stressful life events and drugs. To learn more about each of these situations and how they relate to psychosis, please click here.

IMPORTANT - it is unlikely that people with psychosis will have all of the environmental vulnerability factors listed above! An individual may have one, two, several, or none of the factors listed above and still have a psychosis. This list is not exhaustive - we probably do not yet know all of the different environmental factors that can contribute to the development of a psychosis.

Heterogeneity

Although two people can both be diagnosed with the same psychosis (e.g. schizophrenia), they may not have the same set of symptoms. This is called heterogeneity. One explanation for this heterogeneity is that these two people may have different genetic and environmental vulnerability factors causing the illness.

We have seen that there are many different environmental vulnerability factors, and that each individual with psychosis will have only some of these. Similarly, there seem to be many different genetic vulnerability factors, and each individual with psychosis will have only some of these. So, there are many different potential combinations of genetic and environmental vulnerability factors, which could all lead to the same psychosis.

For example, each shape in the picture below represents a person with a particular psychosis (e.g. schizophrenia). The different shapes and colors represent the different genetic and environmental contributions to the psychosis for each individual.

You may have heard of the stress-vulnerability model of psychosis. This model says that people have different sensitivities to their environments, and in particular to stress in life. Some people are more sensitive to their environment and to stress and are therefore more likely to develop psychosis when exposed to these things. This difference in sensitivity to the environment between different people is thought to be due to different amounts of genetic vulnerability factors. In other words, someone with a large amount of genetic vulnerability is more sensitive to their environment than someone with a small amount of genetic vulnerability. This is shown in the pictures above.

We also can't rule out the possibility that in a very small minority of cases, psychosis might be caused by just genetic vulnerability. Similarly, we can't rule out the possibility that in a very small minority of cases, psychosis might be caused by just environmental vulnerability. This is shown in the pictures below.

While we cannot change the amount of genetic vulnerability we have, we can do something to alter our environmental vulnerability. Reducing stress and/or stopping drug use can lower the chance of a relapse by reducing the environmental vulnerability. This is shown in the picture below.

Also, just as there are vulnerability factors for psychosis, there are probably many protective factors too. Unfortunately our understanding of these protective factors is much poorer than our understanding of the vulnerability factors. Protective factors would make it less likely for a person to develop a psychosis. Some examples of protective factors are: medication, effective coping strategies for dealing with stress, eating the right amounts of good healthy food, getting enough sleep and regular exercise.

Chances for people to develop a psychosis

Psychosis is common. Schizophrenia affects about 1% of the general population, bipolar disorder affects about 1-2% of the general population and major depression affects about 5-10% of the general population.

However, studies show that the chances for developing many types of psychosis are higher for family members of people with a psychosis.

The following statistics show the chances of a person who has a brother, sister, or parent with one of the following disorders, developing these disorders themselves.

Please note - If there is more than one person in your family with one of these disorders, or if there are many kinds of mental illnesses in your family, the chances may be a little different. See the next section "What to do if you are concerned about these chances", for details about how to get more accurate information based on your own family history.

What to do if you are concerned about these chances.

Ask your family doctor or psychiatrist to refer you to the local Medical Genetics department for a genetic counseling appointment.

Genetic counseling is a communication process. A genetic counselor will take a detailed family history and then try to help you understand the illness in your family, appreciate the way genes contribute to the disorder, understand the recurrence risks, and work through decisions appropriate to both you and your families' goals. Genetic counseling does NOT tell people how to live their lives, nor does it make reproductive decisions for people.

Looking to the future in Medicine

There are a number of ways in which finding the genes that increase vulnerability to psychosis might impact treatment and care of individuals with these illnesses.

First, genetic testing may help clinicians with the diagnosis of different types of psychosis and could also lead to better identification of people who are at risk of developing it.

Second, finding the genes that increase vulnerability to psychosis might help us to identify and understand the role of the environmental vulnerability factors that are important in the development of psychosis.

Third, finding the genes that increase vulnerability to psychosis may lead to better treatments, based on a better understanding of the biological mechanisms of psychosis.

Genetic testing
There is no genetic testing available for the different types of psychosis at the moment, and it may still be a long way in the future. This is because researchers still don't know exactly what and how many particular genes increase a person's vulnerability to psychosis. Without that information if would be very difficult to interpret the results of genetic testing.

Gene Therapy
As we have read earlier, a gene with a mutation, can produce proteins that are made incorrectly, or sometimes not made at all. The purpose of gene therapy is to correct the genes with mutations in them that are responsible for causing or contributing to a disease. In its simplest form, gene therapy tries to insert a normal gene (one without a mutation) into the cells of the body that are affected.

Although this may sound very simple, in practice it is a very difficult task due to an inability to effectively and safely deliver the normal gene to the affected cells of the body, even for a disease like cystic fibrosis, where the lung cells are the only cells affected, and are accessible by inhaling medications.

Psychosis involves multiple genes and environmental factors, and because it affects brain cells, which are far more difficult to deliver medication to, gene therapy for psychosis is a long, long way off.

Pharmacogenomics
Each person will respond differently to medications. Some will respond well, others will have side effects and some won't respond at all. The difference in this response is thought to have a genetic basis, and that is what pharmacogenomics is all about. It looks at how different genes play a role in the effectiveness of medications. The aim is to be able to select a drug with the greatest likelihood of benefit and the least likelihood of harm for an individual patient, by looking first at their DNA.

This is probably going to be the first way in which genetic research directly benefits individuals with psychosis and their families because finding the right medication that works well to relieve symptoms without causing nasty side effects has often been a long and painful process of trial and error.

Already, researchers have identified genetic mutations, which have been found to significantly increase the likelihood of a person developing an unpleasant side effect called tardive dyskinesia (a kind of severe tremor) when they are treated with particular antipsychotic medications. This discovery is useful because in the future, people could be tested for these mutations before they are given this drug.

Different research groups around the world are working on trying to find different genetic mutations that make people less likely to respond well to antidepressants and antipsychotic medications.

This is definitely an exciting area in psychosis research, and an exciting time too. Within a generation, there is a very real possibility that we will be well on our way to individualized antipsychotic therapies, and that we will have a much clearer understanding of the functions of the different genes involved with vulnerability to psychosis.