The major psychiatric diseases, schizophrenia, and bipolar disorder have been the subjects of numerous genetic studies.
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Twins, adoption, and family studies have shown that both disorders aggregate in families.
Genetic studies of psychiatric disorders are challenging because these disorders are undoubtedly heterogeneous, reflecting the influence of numerous genetic and environmental factors.
The involvement of genetic factors in schizophrenia and bipolar disorder are presented.
Schizophrenia
It is a severe emotional disorder characterized by delusions, hallucinations, retreat from reality, and bizarre, withdrawn, or inappropriate behavior. (Contrary to popular belief, schizophrenia is not a “split personality” disorder.)
Estimated heritability of schizophrenia is up to 85%.
The risk of schizophrenia among relatives with one schizophrenic proband is eightfold.
This increases to 11-fold for relatives with two schizophrenic probands.
The lifetime risk for schizophrenia among offspring of one affected parent is approximately 8% to 10%, which is approximately 10 times higher than the risk in the general population.
Empirical risks increase when more relatives are affected. For example:
An individual with an affected sibling and an affected parent has a risk approaching 20%
An individual with two affected parents has a risk of nearly 50%
Risks decrease when the affected family member is a second or third-degree relative
The proportion of schizophrenic probands who have a schizophrenic parent is only approximately 5%, which is substantially lower than the risk for other first-degree relatives (e.g., siblings, affected parents and their offspring).
This can be explained by the fact that people with schizophrenia are less likely to marry and produce children than are other individuals.
Thus, substantial selection against schizophrenia occurs in the population.
Twin and adoption studies indicate that genetic factors are likely to be involved in schizophrenia.
Twin studies data show a 47% concordance rate for MZ twins, compared with a concordance rate of only 12% for DZ twins.
When the offspring of a schizophrenic parent are adopted by normal parents, their risk of developing the disease is approximately 10%, which is approximately the same as the risk when raised by a schizophrenic biologic parent.
Large-scale genetic studies have revealed more than 200 loci that are associated with risk of schizophrenia.
The most significant of these associations implicates complement component genes ( C4A and C4B ) located in the MHC region.
These genes are expressed in neurons and affect synaptic function and likely contribute to the decline in synaptic structures observed in the brains of persons with schizophrenia.
Other schizophrenia-associated genes encode components of the dopaminergic and glutamatergic neuronal signaling pathways. These findings are biologically plausible because the major therapeutic drugs used to treat schizophrenia block dopamine receptors.
Bipolar Disorder
It is also known as manic depressive disorder . It is a form of psychosis with extreme mood swings and emotional instability.
The prevalence for bipolar type I in the United States is approximately 1%, but it rises to 5% to 10% among those with an affected first-degree relative.
Twin and family studies show that approximately 60% of the risk for bipolar disorder is attributable to genetic factors, whereas approximately 30% of the risk for unipolar disorder (major depression) is because of genetic factors.
Large-scale studies have revealed more than 20 genes associated with susceptibility to bipolar disorder.
Best-replicated genetic studies implicate genes that encode voltage-gated calcium and sodium channels.
Ion-channel modulating drugs are frequently used as mood stabilizers, lending the genetic results functional plausibility.
Many of the genes associated with bipolar disorder also are associated with schizophrenia. How are schizophrenia and bipolar disorder affected by genetic factors?
