Learning Objectives:
- Briefly define schizophrenia, explain the major presenting symptoms, and describe the five types of schizophrenia.
- Explain the epidemiology of schizophrenia including the lifetime prevalence, prevalence in first, second, and third degree relatives of persons with schizophrenia, incidence, prevelance by gender, age at onset, and geographical distribution.
- Describe current thoughts on the etiology of schizophrenia
- Describe the role of genetic counseling with regard to schizophrenia.
Pretest Questions:
1. What is the lifetime morbid risk of developing schizophrenia?
A. The lifetime morbid risk of developing schizophrenia for the general population is around 10% worldwide.
B. The lifetime morbid risk of developing schizophrenia for the general population is around 0.01% worldwide.
C. The lifetime morbid risk of developing schizophrenia for the general population is around 0.001% worldwide.
D. The lifetime morbid risk of developing schizophrenia for the general population is around 1% worldwide.
2. Choose the correct statement
- A child born in the summer is more likely to develop schizophrenia than a child born in the winter.
- A child of a parent suffering from schizophrenia has a 10% chance of developing the illness
- A child with a paternal uncle suffering from the disease has no greater chance of developing the illness than the general population.
- The peak age of onset for woman is 25 to 35 years while the peak age of onset for men is 10 to 25 years old.
3. Which of the following
Case Study:Mr. and Mrs. D present to their pediatrician with their daughter for her 2 year old well-child visit. The child is healthy and reaching all developmental milestones appropriately. Mr. and Mrs. D are contemplating having a second child. Mr. D is 26 years old and has no significant family history of genetic disorders. Mrs. D is 24 years old and has a 17 year old brother who was recently diagnosed with schizophrenia. The couple wants to know the risk of their children developing schizophrenia.
Family History: Mrs. C has two siblings, a 20 year old sister who is healthy and a 17 year old brother recently diagnosed with schizophrenia – paranoid type. Her parents are healthy with no psychiatric history. No other members of her extended family have been been diagnosed with a psychiatric illness although her maternal great-grandmother had the reputation of being very “eccentric.”
Questions:
What is the definition of schizophrenia?
What are the five types of schizophrenia?
What is the prevalence of schizophrenia in men verses women?
What is the age of onset of schizophrenia in men verses women?
How do twin studies help to estimate the likely heritability of an illness such as schizophrenia?
What is the role of adoption studies in understanding the etiology of schizophrenia?
What is the significance of a maternal uncle with the disease?
What genetic testing could you offer this couple?
Questions:
- What is the definition of schizophrenia?
Schizophrenia is a thought disorder that impairs jusdgement, behavior, and ability to interpret reality. To satisfy the diagnostic requirements of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), the syndrome must continue for at least 6 months, with at least one month of active symptoms present much of the time, and must result in significant impairment of occupational and social functioning. Because of the variability of symptom expression, diagnostic requirements of chronicity, and lack of pathognomonic features, an ED diagnosis of schizophrenia should be provisional at best. As a diagnosis-by-exclusion, schizophrenia must be distinguished from the numerous psychiatric and organic disorders that also can lead to psychotic disturbances in thinking and behavior such as amnesia, dementia, and delusions.
- What are the five types of schizophrenia?
- Paranoid-type schizophrenia is characterized by delusions and auditory hallucinations but relatively normal intellectual functioning and expression of affect. The delusions can often be about being persecuted unfairly or being some other person who is famous. People with paranoid-type schizophrenia can exhibit anger, aloofness, anxiety, and argumentativeness.
- Disorganized-type schizophrenia is characterized by speech and behavior that are disorganized or difficult to understand, and flattening or inappropriate emotions. People with disorganized-type schizophrenia may laugh at the changing color of a traffic light or at something not closely related to what they are saying or doing. Their disorganized behavior may disrupt normal activities, such as showering, dressing, and preparing meals.
- Catatonic-type schizophrenia is characterized by disturbances of movement. People with catatonic-type schizophrenia may keep themselves completely immobile or move all over the place. They may not say anything for hours, or they may repeat anything you say or do senselessly. Either way, the behavior is putting these people at high risk because it impairs their ability to take care of themselves.
- Undifferentiated-type schizophrenia is characterized by some symptoms seen in all of the above types but not enough of any one of them to define it as another particular type of schizophrenia.
- Residual-type schizophrenia is characterized by a past history of at least one episode of schizophrenia, but the person currently has no positive symptoms (delusions, hallucinations, disorganized speech or behavior). It may represent a transition between a full-blown episode and complete remission, or it may continue for years without any further psychotic episodes.
4. What is the prevalence of schizophrenia in men verses women?
The prevalence of schizophrenia is the same in men and women.
5. What is the age of onset of schizophrenia in men verses women?
The peak age of onset in men is 10 to 25 years. The peak age of onset in woman is 25 to 35 years. The onset of schizophrenia is later and the symptomatology is less severe in women than in men. This may be because of the antidopaminergic influence of estrogen. Most of the deterioration that occurs in patients with schizophrenia occurs in the first 5-10 years of the illness and is usually followed by decades of relative stability, although a return to baseline is unusual.
6. How do twin studies help to estimate the likely heritability of an illness such as schizophrenia?
If both members of a twin pair have schizophrenia, they are classified as concordant, whereas if only one member of a twin pair is affected, they are classified as discordant. A disorder is likely to be under genetic influence if concordance rates are higher in monozygotic (MZ) twins, who share 100% of their genes, than dizygotic (DZ) twins, who share 50% of their genes on average. The results of all the major twin studies across several different countries found the concordance rate for MZ twins to be substantially higher than that found for DZ twins. The results from twin studies provide further strong evidence for the importance of genetic factors in the cause of schizophrenia. The lack of 100% concordance among MZ twins suggests, however, that other nongenetic factors also are important.
7. What is the role of adoption studies in understanding the etiology of schizophrenia?
The relative contributions of genetic and environmental risk factors to the cause of schizophrenia can also be dissected by the use of adoption studies. In addition to shared genes, relatives also share an extensive environment in common, including social and cultural behaviors, biologic hazards, and psychological stresses, which could include performed in an attempt to minimize the effect of such common environmental risk factors in family studies of schizophrenia. The combined findings from various adoption studies provide important support for the conclusions derived from family and twin studies that familial clustering of schizophrenia is an expression of shared genetic factors rather than shared environmental factors.
For Discussion:
Questions:
What is known about the inheritance pattern of schizophrenia?
Although results from family, twin, and adoption studies provide overwhelming evidence that genetic factors play a part in the cause of schizophrenia, the exact mechanisms of genetic transmission remain unidentified. Despite the genetic and phenotypic complexity of schizophrenia, much progress has been made. Research has largely excluded the possibility that genes of major effect exist; linkage analysis has provided independently replicated evidence for genes of moderate effect on several chromosomal regions. Association studies suggest that alleles of at least two genes, those encoding D3 and 5HT 2A, confer a small rise in susceptibility to schizophrenia, and there are convergent findings from several different lines of research implicating regions such as 22q11, although no specific causative genes for schizophrenia have been definitively identified yet.
What is the significance of a maternal uncle with the disease?
It has long been known that schizophrenia runs in families. Persons who have a close relative with schizophrenia are more likely to develop the disorder than are persons who have no relatives with the illness. For example, a monozygotic twin of a person with schizophrenia has the highest risk (40% to 50%) of developing the illness. A child whose parent has schizophrenia has about a 10% chance. A person who has an uncle with the disease has a 2% chance of developing the illness. The risk of schizophrenia in the general population is about 1%. (See Figure 1)
What genetic testing could you offer this couple?
Predictive genetic testing is unlikely to be useful in the near future except for some rare pedigrees if a single major locus is identified. One area where genetic testing may be more helpful, however, is schizophrenia associated with VCFS. In most cases, the deletion of 22q11 occurs as a de novo mutation, but in 10% of those affected, it is inherited from a parent, who may have a mild presentation of the syndrome . In such cases, parents could be tested for the deletion, and, if confirmed, testing could be offered to siblings, especially if other clinical features are present.
Should the couple become pregnant, what prenatal testing is available for this fetus?
There is currently no prenatal testing available for schizophrenia.
What role does genetic counseling play for this family?
Given the limits of current understanding, genetic counseling for people with schizophrenia and their relatives must be based on empirical data for most families (eg, risk to second-degree relatives of 4% to 6%, risk to first-degree relatives of 6% to 13%, and risk to an identical twin of 50%). In addition, genetic counseling should inform relatives about premorbid symptoms of schizophrenia and stress the importance of seeking treatment early should psychotic symptoms emerge because there is some evidence for better outcome with early treatment . Relatives could be advised to avoid specific environmental risk factors, such as substance abuse, which may interact with genetic risk (eg, there is evidence that individuals with a familial loading for schizophrenia are more likely to develop psychosis after abuse of cannabis) .
Draw a pedigree of Ms. C’s family
Please see last page.
What web based resources and patient support groups are available for this family?
National Alliance for the Mentally Ill: http://www.nami.org/
National Mental Health Association: http://www.nmha.org/
Schizophrenia.com: http://www.schizophrenia.com/
National Mental Health Consumers’ Self-Help Clearinghouse http://www.mhselfhelp.org/program.html
National Alliance for Research on Schizophrenia and Depression
60 Cutter Mill Road, Suite 404
Great Neck, NY 11021
Phone: 800-829-8289
Web site: http://www.narsad.org 
National Institute of Mental Health Public Inquiries
6001 Executive Boulevard, Rm. 8184, MSC 9663
Bethesda, MD 20892-9663 U.S.A.
1-301-443-4513
TTY 1-301-443-8431
Web site: http://www.nimh.nih.gov/HealthInformation/schizophreniamenu.cfm
National Schizophrenia Foundation
403 Seymour Avenue, Suite 202
Lansing, Michigan 48933
Phone: 800-482-9534
Web site: http://www.nsfoundation.org/
Hyperlinks:
Online Mendelian Inheritance in Man (OMIM): http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
GenTests – National Institute of Health: http://www.genetests.org/
National Institute of Mental Health: www.nimh.nih.gov
Reference articles:
McDonald C - Psychiatr Clin North Am - 01-MAR-2003; 26(1): 41-63
Fig. 1. Risk of Developing Schizophrenia (in percents) from SCHIZOPHRENIA GENESIS: The Origins of Madness by Irving I. Gottesman. © 1991 by Irving I. Gottesman. Reprinted by permission of Henry Holt & Co., LLC., New York, NY.
Fig.2 Pedigree
  |
