Psychiatric Disorders

Schizophrenia is a disorder characterized by psychotic symptoms such as hallucinations, delusions, and disordered thinking, as well as deficits in emotional and social behavior. Numerous family, twin, and adoption studies have provided substantial evidence for genetic factors in the etiology of this disorder. Nongenetic factors also appear to play an important role. The risk for relatives of an individual with schizophrenia is 6.5 percent, nearly eight times the population rate of the disorder. The concordance rate for monozygotic (identical) twins is 45 percent, and for dizygotic (fraternal) twins the rate is 12 percent. The higher rate for monozygotic twins, who share all their genes, is strong evidence that genes play a role in schizophrenia.

Molecular genetic (linkage and association) studies suggest that there are multiple genes with small effects that predispose one to the disorder. In an early study, chromosome 5q was implicated, but was not replicated. Areas on chromosome 6p and 8p have been replicated in at least one follow-up study. More recently, chromosome 1 has been implicated. While no causative genes have been identified, there have been molecular studies that implicate chromosomes 1q, 3p, 5, 6p, 6q, 8p, 10p, 13q, 18p and 22q in schizophrenia. Like other multifactoral diseases, the etiology of schizophrenia involves multiple genes and gene-environment interactions.

Bipolar disorder is characterized by episodes of depression and mania, elevated or irritable mood, and symptoms such as rapid thoughts, grandiose ideas, and reckless behavior. Population, twin, and adoption studies provide evidence for the role of genetics in the etiology of bipolar disorder. First-degree relatives have about a 7 to 10 percent risk of having the disorder once one family member is diagnosed. The concordance rate for monozygotic twins is 60 to 65 percent, and for dizygotic twins the rate is 10 to 15 percent, the same as for non-twin siblings.

One of the first bipolar disorder molecular genetic studies implicated chromosone 11, but this finding was not replicated in several other studies. A similar failure to replicate occurred with the initial reports of linkage on the chromosome X. Regions on chromosome four are reported to show strong evidence of linkage to some bipolar families. Major efforts in the last few years have been focused on chromosome seven and eighteen. Some of the studies have suggested a parent-of-origin effect, with maternal transmission more common than paternal. Both linkage and association studies have implicated chromosomes 4p, 6p, 12q, 13q, 16p, 18p, 18q, 21q, and 22q in bipolar disorder. Major depressive disorder has also been studied, but the underlying genetic factors have not been identified.