Serotonin Transporter Gene Polymorphisms & Obsessive-Compulsive Disorder (Commentary) (Report)

Serotonin Transporter Gene Polymorphisms & Obsessive-Compulsive Disorder (Commentary) (Report)

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 (1,2). However, linkage analysis studies have not been able to confirm 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 efficacy of selective serotonin reuptake inhibitors (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 psychiatry11. 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).

Serotonin Transporter Gene Polymorphisms & Obsessive-Compulsive Disorder (Commentary) (Report)



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