Genetics

Obsessive-compulsive disorder had been viewed as an inherited disorder long before recent advances in molecular biology allowed clinical researchers to isolate the genetic mechanisms of illness (for additional information, see Chapter 14). Genetic factors associated with OCD have been demonstrated in a number of twin, family genetic, segregation, and gene association studies (Wolff et al., 2000). Twin studies are often the best indicator of a genetic diathesis, and the concordance rate for OCD among monozygotic twins has been reported to be as high as 65 percent (Rasmussen and Tsuang, 1986). A familial study compares the risk for OCD in the relatives of a proband with OCD to that of the general population or a control group; if this risk is found to be significantly higher in the relatives, the illness is considered to be familial. The familial rates of OCD and subclinical OCD have been found to be 15 times higher than expected (Pauls et al., 1995; Nicolini et al., 1993), although this demonstration is not in itself sufficient to determine genetic transmission. Segregation analyses use the pattern of illness within a sample of families to ascertain if this pattern could have been predicted from basic Mendelian genetic principles. Evidence of this nature for OCD suggests that some genes contributing major effects are associated with the manifestation of this disorder (Nicolini et al., 1991; Alsobrook et al., 1999). Both linkage analyses and association studies have isolated genetic markers and candidate genes that appear promising in isolating persons with OCD. The next step in understanding the genetics of OCD is the replication of these studies and the localization and characterization of the genes that confer susceptibility. As with other psychiatric disorders, multiple genes are expected to play an etiologic role.

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