Genetic counseling is a health service, which is provided to people who may inherit or pass on (to their children) a hereditary illness. This service is intended to explain the genetic factors of the specific condition as well as to predict the chances of clients developing/passing on the condition. This is known as recurrence risk.  It is the responsibility of the genetic counselor to help people understand these facts. Genetic counseling for psychiatric conditions such as schizophrenia is becoming more wide spread and its use is being successfully demonstrated. Potential clients should be aware that while there are many benefits of genetic counseling, it could also be distressing due to the emotional subjects discussed.  In general, people who have schizophrenia within their families may be interested in learning more about the causes of the condition, and discovering whether they or their relatives will be at risk for developing the condition. Genetic counseling can answer some of these questions.

Schizophrenia is a complex condition, affecting approximately 1% of the general population. The exact causes of schizophrenia are still not well understood, however it is now thought that a number (5 to 10, or more) of different genes, as well as many different environmental influences, are responsible for an individual developing schizophrenia. Therefore schizophrenia is classified as a multifactorial syndrome. This means that schizophrenia can run in some families, although many people with schizophrenia do not have an affected relative.

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Editorial Note: Dr. E. Fuller Torry (not a genetic counselor, but a well-known schizophrenia researcher and advocate) has noted in his book "Surviving Schizophrenia" the following regarding genetic inheritance of schizophrenia,

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Traditionally, genetic counseling has concentrated on conditions with well-known patterns of inheritance, such as Huntington's Disease. Genetic counseling for psychiatric disorders is more complex and was first performed in the early 1980s. At present, genetic counseling is recommended for people with schizophrenia in their families, although it is not known how many people are actually offered these services. Clients needing genetic counseling may see their local counselor or they may attend a hospital, which concentrates on psychiatric conditions.

For example, the University of British Columbia in Canada and Columbia University in New York specialize in genetic counseling for psychiatric conditions. It is possible to find a genetic counselor with expertise in schizophrenia by looking on the National Society of Genetic Counselors (NSGC) web site (www.nsgc.org). All genetic counselors listed on the NSGC web site are registered with the NSGC and should have an Masters of Science (MS) in genetic counseling. Additionally, most counselors are certified or certifiable by the American Board of Genetic Counselors. Moreover, counselors with a special interest in psychiatric conditions are often registered with the NSGC psychiatric special interest group, which helps them maintain up-to date knowledge.

Calculating the recurrence risks (or the risk that schizohprenia will re-occur in a family - either in future children a couple may have, or in other existing family members) is complex. It is not yet possible to test whether an individual has specific genes (though this is changing quickly), which would increase their chances of developing schizophrenia. Therefore genetic counselors must use empiric data (figures obtained by counting how many people with schizophrenia also have specific relatives with schizophrenia), coupled with their knowledge of the client's family history. Specifically a genetic counselor may calculate risks of developing schizophrenia by using a Bayesian calculation (a type of statistical estimate) on the basis of empiric data and the client's family mental health history, alternatively it may be possible for a genetic counselor to see a clear inheritance pattern from the family history. Generally, the family history review will try to look back for three or four generations.

The counselor will also gather information about any other brain disorder diagnoses (e.g. "mental breakdown", depression, temporary psychosis, depression, bipolar disorder, schizo-affective, etc.) in the family, as these can complicate the inheritance patterns. When talking with the counselors you should be as comprehensive as possible - including all information about family mental health backgrounds that you can dig up - the more information that you can provide the counselors, the better the estimate of the risks. Some information from previous generations may be vague or not formally diagnosed (for example, in the early 1900's a person might have been said to have a "mental breakdown" - which resulted in them being temporarily treated in a psychiatric hospital, given shock treatments and released; or maybe you had a "eccentric uncle" that lived by himself in a cabin away from society and only very rarely socialized with family, and spoke of conspiracy theories when he did talk. This type of information should be conveyed to the counselors. Counselors will consider these alternative diagnoses when calculating the schizophrenia recurrence risks (i.e. the risk that schizophrenia will hit again in the family).

Generally, a genetic counseling session will last about an hour and should be covered by health insurance in the US, while in the UK and Canada the national health services provide counseling. Genetic counseling provides clients with specific information, as well as helping clients to understand and process their emotions. The benefits for clients include gaining a thorough understanding of the causes of schizophrenia, personalized recurrence risks, correction of misconceptions and the opportunity to explore resulting emotions.

Genes linked to the development of Schizophrenia

Specific genes have not been shown to directly cause schizophrenia, however, numerous studies have shown a variety of chromosomes to be involved in the inheritance of schizophrenia, and a number of these studies have been confirmed by independent research groups.  These chromosomes are thought to contain certain genes, which increase the chance of an individual developing schizophrenia. The chromosomes thought to contain these genes include (²⁰): chromosomes 22, 1, 18, 15, 14, 13, 12, 11, 10, 8, 6, 5, 3.

While the specific chromosomal regions are (²⁰):

22q12.3, 22q11.2, 22q11-q13, 1q42.1, 18p, 15q15, 14q32.3, 13q34, 13q32, 12q24, 11q14-q21, 1q21-q22, 10q22.3, 8p21, 6q13-q26, 6p22.3, 6p23, 5q11.2-q13.3, 3p25.

With this many chromosomes involved, the inheritance of schizophrenia is complex.  There is not just one gene that causes schizophrenia. Instead, inheriting several genes causes an individual to have a higher chance of developing this condition. Genes which are thought to increase the chance of an individual developing schizophrenia include(²): the regulator of protein signaling 4 (RGS4), D-amino acid oxidase (DAAO), Dopamin receptor (DRD3), seratonin 2a receptor (5HT2a) and Catechol-O-methyl transferase (COMT). These genes are generally thought to be involved in the regulation of chemicals within the brain. If an individual inherits a combination of these, or other implicated genes, and is then exposed to the correct environmental factors, they may develop schizophrenia.

Environmental risk factors for schizophrenia include (^2,31): being an identical twin, being born in winter, poor childhood health, advanced paternal age, drug and/or alcohol abuse, social factors (including immigration and living in urban areas), head injury, trauma, small head circumference and a variety of pregnancy factors. (see environmental risk factors for schizophrenia for more information). Pregnancy factors include(^2,7): preeclampsia (a blood pressure complication), low maternal weight, diabetes, bleeding in pregnancy, rhesus incompatibility (a difference in the blood type of mother and baby), brain damage caused before birth, viruses affecting the fetus, fetal distress and viral infections of the CNS (brain and spinal cord) before or soon after birth. (See pregnancy risk factors for schizophrenia for more information)

It is also believed that there may be biological subsets of schizophrenia, which means that different genes may cause people to have specific symptoms. One distinct subgroup of schizophrenia is known to be associated with a gene in the chromosome region 22q11.2(⁸). The deletion of this gene causes a syndrome known as DiGeorge, and 25% of the people with this syndrome are known to develop schizophrenia.   It is thought that as the genetics of schizophrenia become better understood, other biological subgroups will be identified.

Overall, the exact cause of schizophrenia is difficult to determine, however, it is very clear that there is a genetic component to this disorder. It would therefore seem important that individuals with schizophrenia or individuals who have a family member with schizophrenia, receive genetic counseling.  To date many people have published studies supporting the use of genetic counseling for people with schizophrenia and their relatives. These studies include: Tsuang etc al (2001), Papadimitriou & Dikeos (2003), A Reveley (1985), Austin & Honer (2004), Whiteford & Price (1987,) and Hogdkinson, et al (2001). Click on the following link for the latest news on Genetics and Schizophrenia

Who might see a genetic counselor (¹²)?

There are many reasons why people with schizophrenia in their family might see a genetic counselor. Some of the people who might see a counselor include:

• Couples whose relative has schizophrenia and who would like information about the risk to their future children.
• Individuals whose relative has schizophrenia and who wants to know whether they are likely to develop it as well.
• Adoptive parents whose child has a biological parent with schizophrenia and who want to know the risk for that child to develop the condition.
• People with schizophrenia who want to know the risk to their children
• People who want to know the effect of taking psychiatric drugs during their pregnancy
• Individuals working at Children’s organizations, who need to provide accurate information to their clients

Many of the people who seek genetic counseling for schizophrenia are considering having children, as the presence of schizophrenia in their family may effect their family planning decisions. Some people decide to have children earlier than normal, others to have more children than they would normally (to compensate for their family member not having their own) and some people chose not to have children at all. The decision of whether to have children may depend on how the couple views schizophrenia and what they perceive to be the chance of developing schizophrenia.  People with schizophrenia often view it as much less of a burden than their relatives do. Consequently the relatives of people with schizophrenia may be more concerned about passing on genes that increase the chance of their children developing the condition. Discussing these decisions with a genetic counselor can help clarify emotions and accurate risk.

Additionally, genetic counseling is very useful for explaining the causes of schizophrenia and correcting possible misconceptions that many people have.  For example, some people believe that genetic disorders are untreatable and that if someone has the gene they must develop the disease. This is NOT true. Many genetic disorders can be treated and not everybody with genes for schizophrenia will develop the condition. There have been numerous cases involving identical twins in which one twin inherits schizophrenia and the other twin does not.  As identical twins must have the same exact genes, we suspect that if developing schizophrenia were a result of genetic inheritance alone that both twins would develop the disease.  The other twin actually only develops schizophrenia about half the time.

Counseling sessions can also suggest preventative measures for schizophrenia, such as(¹): safe guarding the health of children who are at risk for developing schizophrenia, avoiding high stress levels, and avoiding other environmental risk factors.  It is also possible to help parents look for early warning signs in their children and get early diagnostic testing for schizophrenia, or periodic testing for schizophrenia. Genetic counseling for clients with schizophrenia in their families can also help demystify schizophrenia and therefore decrease the effects of potential stigma for the family.  Finally genetic counseling may improve adherence to the treatment plan in some patients, once they better understand schizophrenia.

 The steps of a genetic counseling session are (^8,33):

1.      Gathering information

2.      Assessing risk

3.      Conveying information

4.      Providing support and facilitating decision making

5.      Follow up support

1.          Gathering Information / Family History

Information about the client’s family history and diagnoses may be gathered at the beginning of the appointment. Alternatively, the genetic counselor may telephone the client before hand, enabling the counselor to obtain any necessary medical records prior to the appointment. 

 In this stage the genetic counselor will ask the client about their own health history, as well as their family history, and obtain as much information as necessary. This information will be used to construct a diagram of the family history called a pedigree.

 At this point, it is important for the genetic counselor to clarify the actual diagnosis of any family members with schizophrenia, as schizophrenia can be confused with similar conditions. In order to get an accurate diagnosis, it may be necessary to obtain the psychiatric and / or medical records of the individuals with schizophrenia.

Assessing Risk

 Calculating the chance that a specific relative will develop schizophrenia is a complicated process. As a specific inheritance pattern is not generally recognizable, risk is calculated using observations of how schizophrenia is passed down in other families with the condition. This is done by, counting how many people with schizophrenia also have specific relatives with schizophrenia. Therefore these figures may not always apply completely to a particular family, although they will give an indication of the family’s risk.  Additionally, individuals whose schizophrenic symptoms develop earlier and are more severe may have more genes for schizophrenia, which would increase the risk to their relatives. Data on recurrence risks vary depending on the study, as well as many other factors. Therefore the following table gives only very general figures for the chance of an individual developing schizophrenia

Relationship to an individual with schizophrenia	recurrence Risk (%) *
General population	1
Parents	1-6
Siblings	7-14
Offspring of one parent	6-16
Offspring of two parents	35-46
Second Degree Relative (e.g. Aunt /uncle)	2-8
Third Degree Relative (e.g. First cousin)	1-6

* These are averaged figures from several studies. For more specific figures and explanation, contact your nearest genetic counselor.

The chance of an individual developing schizophrenia also decreases as they become older and remain symptom free. This is because people normally show symptoms of schizophrenia in their early 20s, if they are male, or late 20s, if they are female. For example, a person over 55 who is symptom free has basically no chance of developing schizophrenia, while a person over 40 has a much-reduced risk (²⁶). Additionally, recurrence risks can be complicated by the presence of other related mental illnesses in the family such as schizoaffective disorder. Therefore it is very important that a competent counselor calculates the recurrence risks individually for each client.

 The subgroup of schizophrenia associated with DiGeorge syndrome (also known as velocardiofacial syndrome) has very different recurrence risks. If this syndrome is identified, other family members can be screened to see whether they carry the gene.  It is also possible to refer patients for examinations for symptoms related to DiGeorge syndrome. The chance the child of a person with DiGeorge syndrome will also develop DiGeorge syndrome is 1 in 2 (⁸). However, this does not mean that the child will definitely develop schizophrenia as only 25% of people with DiGeorge develop schizophrenia. Therefore the child of someone with DiGeorge Syndrome actually has a 1 in 8 or 12.5% chance of developing schizophrenia. In the future as we are able to determine more precise inheritance for other subgroups of schizophrenia, it should be possible to give these families more precise figures.

Conveying Information

 The genetic counselor will explain what we know about the causes of schizophrenia. They will also explain what the recurrence risks are and what those risks mean to that family, as well as providing information and helping individuals understand more about schizophrenia. It is hoped that this information may help alleviate some of the guilt and self-blame some relatives, especially parents, may feel.  Being well informed about the causes of schizophrenia may also help decrease the burden of stigma, which some relatives may feel.

Providing support / facilitating decision making

 One of the primary roles of a genetic counselor is to provide support and to ensure that the individual is able to make any necessary decisions. Moreover, the counselor discusses the emotions arising from the information provided which may help the client make any necessary decisions. Clients often see a genetic counselor when they are trying to decide whether to have children. Therefore the counselor will help them discuss their emotions and hopefully come to a decision. Genetic counseling is completely non-directive therefore at NO time will a genetic counselor influence a client or favor a particular decision.

 In the future, as with most diseases, the diagnosis and treatment approaches look likely to continue to get better. In the imediate future, Psychopharmacogenomics aims to develop tailored medications that alleviate symptoms without the side effects. 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. The FDA recently approved the first genetic test (for CYP2D6, which is involved with fast/slow metabolism) which can help physicians to select a dose of antipsychotic medication to prescribe! This is merely the tip of the iceberg however, and this area of research holds great promise.

If specific genes linked with schizophrenia are validated by additional research studies, it MAY be possible to test for these genes either before birth, or before an individual shows symptoms. This testing would allow the genetic counselor to more accurately determine the chance of an individual developing schizophrenia, and work with psychiatric doctors to potentially take actions to prevent the development of schizophrenia. This has the to potential to create ethical and moral dilemmas for the client and therefore the genetic counselor would help the client to make the necessary decisions. Another goal of medical research today is to develop additional therapies to prevent or cure people who have the genes that predispose them towards getting schizophrenia. The goal of gene therapy research is to allow slight targeted modification of sections of genes (that predispose a person towards develping schizophrenia) to an alternative version of the same gene (like editing a mistake in computer document with a word processor). If this were done early in life, it could dramatically reduce or potentially eliminate the risk of schizophrenia for a child. Another important area of research is that of stem cell research. The goal of this research is to very clearly understand the process by which brain development may be impacted by specific variations of genes, and potentially reverse the damage caused to the brain by inserting new stem cells into the brain in targeted regions. (see stem cell research and schizophrenia for more information)

Follow up

 Follow up to the genetic counseling session can take many forms. Frequently, genetic counselors will write a letter to the client containing all the facts that were discussed during the session. The genetic counselor may also call the patient or arrange another appointment to discuss any outstanding concerns. People will frequently leave a genetic counseling session and then realize that they have more questions or are concerned about something. As a result, genetic counselors consistently encourage their clients to contact them if they have any questions or worries.

 Current Research

 Currently many research groups are studying the genetics of schizophrenia. Several are also investigating the psychosocial issues related to the condition, including the importance of genetic counseling. Hopefully these studies will improve the understanding of the genetics of schizophrenia and the role genetic counseling should play with these people.

Research Projects^**

Genetic counselors at the University of British Columbia are currently performing an online survey researching the genetic knowledge of people with psychosis. This survey mainly concentrates on ascertaining the genetic knowledge of respondents and involves researching all types of psychosis.

 A researcher at Sarah Lawrence College is investigating the perceptions of people with schizophrenia and their relatives, relating to genetic counseling. This study intends to identify when and why people with schizophrenia in their families see genetic counselors, as well as to understand clients’ experiences and opinions about genetic counseling.

 This summer, researchers at the University of British Columbia intend to perform a trial of genetic counseling for patients with schizophrenia. This research will focus on the requirements of the genetic counseling session and patients’ reactions to counseling. Hopefully, this new information will help psychiatric genetic counseling to be more focused on the needs of these clients.

How to Contact a Genetic Counselor

 There are different ways to make an appointment with a genetic counselor, depending on your country of residence. The first step is usually to see your primary health care provider (GP in the UK) and ask whether genetic counseling would be relevant for you. They will then normally refer you to your nearest genetic counselor. For more information about genetic counseling or to find a genetic counselor, please click on one of the following links:

www.agnc.co.uk   (UK)

www.nsgc.org (US)

www.marchofdimes.com (US)

www.bshg.org.uk (UK)

www.genetics.com.au (Australia)

www.cagc-accg.ca (Canada)

 Universities that offer genetic counseling

References

Schizophrenia and Genetic Risks - designed for families (Booklet in .PDF format) - this booklet is rather old (probably over 5 years old - so a out of date considering how fast the field of genetics is moving - but written by knowlegeable people).

(**) Information from personal correspondence with researchers

 (Note - all the following papers should have abstracts for the articles at www.pubmed.org

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