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.
Outlined below are a few studies that support the theory that
psychosis is caused by a combination of genetic and environmental
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 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
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.
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
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.
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.
Person with a moderate amount of genetic
vulnerability and a moderate amount of environmental vulnerability.
Person with a small amount of genetic
vulnerability, and a large amount of environmental vulnerability.
Person with a large amount of genetic vulnerability,
and a small amount of environmental vulnerability
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.
A person with psychosis caused just by genetic
A person with psychosis caused just by environmental
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.
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.
Chances to develop
15% - 30%
70% - 85%
10% - 15%
85% - 90%
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
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
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
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.
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.
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
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
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.