Learning Objectives:
- Briefly define bipolar disorder (BD) and explain the major presenting symptoms
- Explain the epidemiology of bipolar disorder including the lifetime prevalence, prevalence in first degree relatives of persons with bipolar disorder, prevalence by gender, and age at onset
- Describe current thoughts on the etiology of BD
- Describe the role of genetic counseling with regard to BD
Pretest Questions:
1. What is the lifelong prevalence rate (in the United States) of developing BD?
A. 1%
B. 10%
C. 0.01%
D. 0.1%
2. A person with a first degree relative with BD is how much more likely to develop the disease than the general population?
A. No more likely to develop the disease than the general population
B. Twice as likely to develop the disease than the general population
C. Seven times more likely to develop the disease than the general population
D. Twenty times more likely develop the disease than the general population
3. Which of the following characterizes the genetic pattern of inheritance of BD?
A. Autosomal Dominant
B. X-linked Recessive
C. Mitochondrial Inheritance
D. Unknown, with multiple different genetic loci implicated
Case Study:
Ms. R. is a 28 year old woman who has bipolar disorder. Her symptoms are well controlled by medication and through adjustments to her lifestyle. She has recently married, and she and her husband, Mr. R. are wondering whether their children will have bipolar disorder. Ms. R has an aunt and a first cousin with the illness. She is aware that bipolar disorder 'runs in the family.'
Before starting a family, Mr. and Ms. R. schedule an appointment with their primary care doctor. The primary care doctor will take a family history and address the family’s concerns. The doctor should initiate a conversation about issues that could arise during pregnancy such as how the stress of pregnancy and a new baby might affect Ms. R’s mental health. The primary care doctor will refer the couple to a genetic counselor and suggest that Ms. R plan to speak to her psychiatrist about her medications before becoming pregnant.
Questions For Discussion:
- What is bipolar disorder? Describe the three classifications of BD.
- Who gets BD?
- What is the prevalence of BD in men verses women?
- What is the age of onset of BD?
- What are the risk factors for developing BD?
- What is known about the etiology of BD?
- What genetic testing could you offer this family?
- What resources could you offer this family?
1. What is bipolar disorder?
Bipolar disorder, or manic-depressive illness, is characterized by periods of mania (with exaggerated euphoria, irritability, or both and episodes of depression. To qualify for a diagnosis of bipolar disorder, only one episode of mood elevation needs to be reported.
Although chemical imbalances in the brain are a key component of bipolar disorder, it is a complex condition that involves genetic, environmental and other factors that causes unusual shifts in a person's mood, energy, and ability to function
Bipolar disorder is classified as bipolar disorder I, bipolar disorder II, or cyclothymic disorder according to the pattern and severity of the symptoms. Though considered t hree distinct conditions, each is most likely a part of a spectrum of the disease and patients with one type may develop another. Some experts believe these conditions are actually separate disorders with different biologic factors that account for their differences.
- Bipolar disorder I is characterized by at least one manic episode, with or without major depression. In 60% to 70% of cases, manic episodes precede or follow depressive episodes in a regular pattern. Episodes are more acute and severe than in the other two categories. Without treatment, patients average four episodes of dysregulated mood each year. With mania, either euphoria or irritability may mark the phase. In addition, there are significant negative effects (such as sexual recklessness, excessive and impulsive shopping, and sudden traveling) on a patient's social life, performance at work, or both. Untreated mania lasts at least a week and it can last for months. Typically, depressive episodes tend to last six to 12 months, if left untreated.
- Bipolar disorder II and Hypomania is characterized by at least one episode of hypomania and at least one episode of major depression. With hypomania the symptoms of mania (typically euphoria) appear in milder forms and are of shorter duration. Patients do not experience manic or mixed episodes, and most return to fully functional levels between episodes. However, bipolar II patients have a more chronic course, significantly more depressive episodes, and shorter periods of being well between episodes than patients with type I have. It is highly associated with the risk for suicide.
- Cyclothymic disorder is not as severe as either bipolar disorder II or I, however the condition is more chronic. Hypomanic symptoms tend toward irritability as compared to the more euphoric symptoms of bipolar II. The disorder lasts at least two years, with single episodes persisting for more than two months. Cyclothymic disorder may be a precursor to full-blown bipolar disorder in some people or it may continue as a low-grade chronic condition.
2. Who gets BD?
Bipolar disorder affects approximately 2.3 million adult Americans. In the United States, the lifelong prevalence rate of bipolar disorder in the United States is 1-1.6%. The 2 types of disorders differ in adult populations, with approximately 0.8% having BPI and 0.5% having BPII. Internationally, the lifelong prevalence rate is 0.3-1.5%.
Men and women are equally likely to develop this disabling illness. While BPI occurs equally in both sexes; rapid-cycling bipolar disorder (4 or more episodes a year) is more common in women than in men. Incidence of BPII is higher in females than in males.
The age of onset of MDI varies greatly. Both children and adolescents can develop bipolar disorder. It is more likely to affect the children of parents who have the illness. The age range for both types of bipolar disorders is from childhood to 50 years, with a mean age of approximately 21 years. Most cases commence when individuals are aged 15-19 years. The second most frequent age of onset is 20-24 years.
3. What are the risk factors for developing BD?
The risk of developing bipolar disorder increases with the biological closeness of the relationship. First-degree relatives have greater risk of being affected than do second-degree relatives.Complex causes of the disorder and from an iincomplete understanding of how the illness begins make it difficult to predict the risk of developing BD.
The following estimates have been determined:
- The risk to the offspring of two parents who do not have the illness and have no affected relatives is about one percent (1 out of 100).
- If one parent has bipolar disorder, the risk to offspring is about five percent. It can be as high as 14 percent if other relatives, such as an aunt or uncle, also are affected.
- In the unusual case where both parents have bipolar disorder, the risk to offspring is approximately 30 percent, but can increase slightly if other relatives are affected.
- The siblings of a person with bipolar disorder have roughly an 8 percent risk of developing the illness. The risk increases markedly, however, if other close relatives also are affected.
4. What is known about the etiology of BP?
Bipolar disorder, especially BPI, has a major genetic component. First-degree relatives of people with BPI are approximately 7 times more likely to develop BPI than the general population. Offspring of a parent with bipolar disorder have a 50% chance of having another major psychiatric disorder. Twin studies demonstrate a concordance of 33-90% for BPI in identical twins. Adoption studies prove that a common environment is not the only factor that makes bipolar disorder occur in families. Numerous genetic studies of BPI disorder suggest multiple different genetic loci, but, as yet, no genes have been definitively identified. New findings suggest an independent genetic liability for psychosis shared by both mood and schizophrenia spectrum disorders.
The evidence for the exact role of genetics in manic depression is still accumulating. Genes located on several different chromosomes have been associated with manic depression in different families: the long arm of chromosome 12 (12q), the short arm of chromosome 4 (4p), the long arm of the X chromosome (Xq), the short arm of chromosome 18 (18p), the short arm of chromosome 16 (16p) and on the long arm of chromosome 21 (21q). Recent evidence from studies conducted by McMahon, F. J. and other in 2001 (Arch. Gen. Psychiat. 58: 1025-1031), indicates that changes in a gene located on the long arm of chromosome 18 (18q) are linked to bipolar type II.
Ten major research groups worldwide are currently studying DNA and clinical data from over 650 individuals with bipolar disorder and related conditions in an effort to find genes that confer vulnerability to bipolar disorder.
Multiple biochemical pathways likely contribute to bipolar disorder, which is why detecting one particular abnormality is difficult. A number of neurotransmitters have been linked to this disorder, largely based on patients' responses to psychoactive agents. Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal axis involved in homeostasis and the stress response also may contribute to the clinical picture of bipolar disorder.
Psychodynamic theories include the hypothesis that the dynamics of major depressive illness have a common basis with depression as the manifestation of the loss and mania serves as a defense against the feelings of depression.
Environmental influences are also believed to contribute to the cycle of BD either independently or by exacerbating an underlying genetic or biochemical predisposition. Pregnancy is a particular stress for women with a history of a major depressive illness and increases the possibility of postpartum psychosis.
6. Is genetic testing available?
Not yet. Much more research is necessary before tests for genes associated with bipolar disorder can be developed, even for those who have a family history of this illness.
Even if research uncovers one or two genes that become the basis for a test, those genes might not be the only ones that make a person susceptible to the disorder. It is important to remember that a negative genetic test will not guarantee that one will be free of bipolar disorder and that some people who have a positive test may never be affected.
Our ability to predict the onset of this disease will be limited, as researchers do not yet completely understand the influence of a person's environment on the onset of bipolar disorder.
If tests do become available, they should be conducted only by qualified laboratories. In addition, testing should occur only if all of the parties involved, including family members, receive sound genetic counseling and education. Several professional organizations are working now to develop the necessary educational and counseling programs so they will be in place if and when genetic testing becomes possible.
6. What role does genetic counseling play for this family?
Families affected by bipolar disease face a number of complicated issues when they consider having children. Certainly, it is important to understand the genetic risks.
Qualified genetic counselors can provide risk information, which will vary from person to person. Equally as important, qualified genetic counselors can help individuals or couples address other significant questions, for example:
- How might pregnancy affect both parents?
- If the mother has bipolar disorder, how will pregnancy affect the treatment of her illness?
- What medications are safe to take during pregnancy?
- How will pregnancy and the period right after delivery affect other aspects of the mother's treatment?
- How will having a child affect the illness of the mother or father with bipolar disorder? Can the affected person(s) handle the responsibilities of parenthood?
- What will happen if symptoms get worse during the pregnancy or after the baby arrives?
The final decision about whether to have a child, of course, is up to the individual and his or her spouse or partner. But when making this decision, one should be aware of its impact on others, such as family members who provide support.
Good genetic counseling will help ensure that the person with bipolar disorder considers all relevant issues before arriving at a decision about becoming a parent.
7. What resources and support groups are available for this family?
- National Institute of Mental Health (NIMH)
Office of Communications
Information Resources and Inquiries Branch
6001 Executive Blvd, Rm 8184, MSC 9663
Bethesda, MD 20892-9663
Phone: (301) 443-4513; Fax: (301) 43-4279
Fax Back System, Mental Health FAX4U: (301) 443-5158
E-mail: nimhinfo@nih.gov; Web site: http://www.nimh.nih.gov
- National Depressive and Manic-Depressive Association www.bipolarnetwork.org
 Call (310-794-9913).
- Child & Adolescent Bipolar Foundation www.bpkids.org
  Call (847-256-8525).
Hyperlinks:
Reference articles:
Bipolar disorder: Patient Handout. MDConsult. Retrieved on April 24, 2005 from
http://home.mdconsult.com/das/patient/view/46670560-2/10041/9429.html/top?sid=360766693
Bipolar Disorder Research at the National Institute of Mental Health Retrieved on April 25, 2005 from http://www.nimh.nih.gov/publicat/bipolarresfact.cfm
Bipolar disorder. The Foundation for Genetic Education and Counseling (FGEC). Retrieved on April 25, 2005 from http://www.fgec.org/resources/bipolar.html
Cadoret, RJ. Evidence for genetic inheritance of primary affective disorder in adoptees. Am. J. Psychiat. 135: 463-466, 1978.
Mental Illness: Schizophrenia and Manic Depression. Center for Genetics Education. Retrieved on April 25, 2005 from http://www.genetics.com.au/factsheet/50.htm
Soreff, S. Bipolar Affective Disorder. Emedicine. Retrieved on April 25, 2005 from http://www.emedicine.com/med/topic229.htm |
