Obsessive Compulsive Disorder (ocd) Is a Neuropsychiatric Condition That Has Been Shown to Be Heritable and for Which a Major Gene Effect Has Been Reported Based on Segregation Studies

Abstract

1,2. However, linkage BLOCKINanalysis BLOCKINstudies BLOCKINhave BLOCKINnot BLOCKINbeen BLOCKINable BLOCKINto BLOCKINconfirm a locus for OCD 3. The most promising candidate genes for OCD at the present time are in the serotonin system and the glutamate system 4. The SCL6A4 gene has been the most extensively studied functional polymorphism in psychiatry, providing worldwide evidence of its importance in several disorders, such as OCD. The BLOCKINefficacy BLOCKINof BLOCKINselective BLOCKINserotonin BLOCKINreuptake BLOCKINinhibitors (SSRIs) in the treatment of OCD has lead to the hypothesis of a serotonergic dysfunction in this disorder 5. Since SSRIs acts on the serotonin (5HT) transporter (5HTT), it has been suggested that the 5HTT gene (SCL6A4), located on chromosome 17q12 6 , could be a good candidate for OCD 7-9. A functional polymorphism in the promoter region has been described 10. This 5HTT-linked polymorphic region (5HTTLPR) is situated in a GC-rich region composed of 20-23 bp repeat units. The biallelic polymorphism consists of an insertion (long allele, " l ") or a deletion (short allele, " s ") of 44 bp. The serotonin transporter (SERT) is probably the most widely studied gene in psychiatry 11. Previous studies have reported the " l " allele is as characterized by increased transcriptional activity as well as increased basal re-uptake of 5-HT in vitro compared with the short form of the 5HTTLPR 10. A possible association between 5HTTLPR polymorphism and OCD has been studied by some research groups. Billett et al 7 could not find an association in 72 OCD patients compared to 72 controls. However, a relative increase (not statistically significant) of homozygous (" l " allele) in the OCD group was observed. Bengel et al 8 , reported that OCD patients were more likely to carry two copies of the long allele (" l "), compared to controls. A study by McDougle et al 9 using a family-controlled transmission disequilibrium test (TDT), reported a predominant " l " allele transmission in 24 heterozygous parents to their OCD affected sibs. A preferred " l " allele transmission was also observed in 10 out of 13 SSRI non-responders. In addition, an analysis of SCL6A4 coding region has not revealed differences in OCD patients 12. As suggested by these studies of a possible relationship between OCD and the " l " allele, our group analyzed the 5-HTTLPR polymorphism in Mexican OCD patients using a case-control methodology. Besides, we analyzed alternative methods that employ family-based …