Genetic aspects of obsessive-compulsive disorder

Over the past 2 decades, the interest in genetic mechanisms underlying many psychiatric disorders has resurged. The changes in the understanding of obsessive-compulsive disorder (OCD) reflect this shift of perspective. Although OCD is a syndrome that is quintessentially psychiatric, a genetic dimension has been increasingly recognized, meriting study in through the concepts and tools of human genetics and molecular biology. This article summarizes the evidence that has led to a better understanding of the nature of inherited factors in OCD. The familial nature of OCD has been observed since the 1930s. Although major psychiatric diseases typically exhibit a complex mode of transmission, genetic factors consistently have been associated with OCD in twin, family genetic, segregation, and gene-association studies. Results from all analyses to date suggest that the underlying genetic mechanisms for OCD involve genes of major effect. OCD is a psychiatric disorder characterized by uncontrolled obsessions (i.e., intrusive and senseless thoughts) or compulsions (i.e., repetitive stereotyped behaviors) sufficiently severe to interfere with a person's ability to function on a daily basis, leading to significant disability. 4 OCD was initially thought to be rare in the general population, 3 but epidemiologic data from surveys of different populations consistently have indicated a prevalence of OCD from 1.1% to 3.3% in the general population 20,29,46 —much higher than was originally believed. In the United States alone, OCD is estimated to affect nearly 5 million citizens, with a resultant annual economic impact of $8.4 billion, 18 including treatment costs and lost productivity, making it a significant public health issue OCD has been called a "hidden epidemic." 26 Although research on the biology and treatment of OCD has increased greatly during the past decade, the cause of this disorder remains largely unknown; the genetic basis of OCD certainly is not yet fully understood. Family and twin studies show that OCD is a familial disease (for review, see Nicolini et al 38 ); segregation analysis data have supported the notion of a primary gene mechanism. 1,14,39 Some forms of OCD, such as that in patients with a predominance of symmetry and ordering symptoms, seem to better fit this major gene pattern. 1 Progress in molecular genetic studies has highlighted some genes as potential candidates associated with the genetic transmission of susceptibility to OCD. 2,6,7,9,27,28,36 Although important contributions have come from research on the environmental factors influencing psychiatric disorders, 12 the genetic study of such diseases should yield information about the underlying biology. Genetic information is directly related to treatment and prevention; early identification of vulnerability to psychiatric illness is expected to allow for the development of early intervention and prevention strategies.