5HT1Dβ Receptor gene implicated in the pathogenesis of Obsessive-Compulsive Disorder: further evidence from a family-based association study

Abstract

Obsessive-Compulsive Disorder (OCD) is a psychiatric condition with strong evidence for a genetic component and for the involvement of genes of the serotonin system. In a recent family-based association study we reported an association between the G allele of the G861C polymorphism of the 5HT1D␤ receptor gene and OCD. The aim of the present study was to further investigate for the presence of linkage disequilibrium between each of two polymorphisms of the 5HT1D␤ receptor gene and OCD in a larger sample of OCD families. In a total of 121 families the G861C and the T371G polymorphisms of the 5HT1D␤ receptor gene were genotyped using standard protocols. The genotyping data were analyzed with a new extension of the Transmission Disequilibrium Test (FBAT). The phenotypes considered in the analyses were the diagnosis of OCD and two quantitative phenotypes related to the diagnosis and clinically relevant, ie, the age at onset and the severity of OCD symptoms. We confirmed the previously found preferential transmission of the G861 allele to the affected subjects (z = Obsessive-Compulsive Disorder (OCD) is a severe psychiatric condition affecting up to 3% of the general population lifetime. 1 The etiology of OCD remains obscure. However, there is strong evidence for a genetic component, 2 and for the involvement of the serotonin (5HT) neurotransmission. [3][4][5] The 5-HT1D␤ receptor is a terminal auto-receptor involved in the regulation of 5HT release. The acute administration of non-selective (ie, mCPP) or selective (ie, sumatriptan) ligands of the 5HT1D␤ receptor induces a transient worsening of OCD symptoms. 4,6,7 On the other hand, the chronic administration of sumatriptan was found to improve symptoms in some OCD patients resistant to conventional pharmacotherapy. 8 We recently reported on significant linkage disequilibrium between the G861 allele of the 5HT1D␤ gene and OCD. 9 The specificity of this association has been supported by a more recent study reporting no association between the same marker and bipolar disorder. 102

A common polymorphism in serotonin receptor 1B mRNA moderates regulation by miR-96 and associates with aggressive human behaviors

“…Indeed, the absolute role of the HTR1B gene in behavior has been difficult to ascertain, and research on HTR1B has yielded conflicting results in terms of its pharmacology and genetics. Genetic studies have shown an association between variation in the HTR1B gene and a number of phenotypes, including attention deficit hyperactivity disorder, [28][29][30] obsessive compulsive disorder, 31 antisocial alcoholism, 32 substance dependence and major depression. 33 However, many of the association findings have been inconsistent, [34][35][36] and this may be due to an incomplete awareness of the extent of functional variation within the HTR1B gene.…”

Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive–compulsive disorder as an example of overlapping clinical and genetic heterogeneity

“…The most informative models have used knockout or transgenic mouse models of Sapap3, 5-HT 2C , D1CT and DAT described below, in addition to Slitrk5 [171], and Hoxb8 [172]. In addition, pharmacological assessments in mouse models suggest a possible role for 5-HT 1B receptors in OCD [173,174], with some evidence for a role for 5-HT 1B (5-HT 1Db ) in OCD from human studies as well [175,176]. Further, trichotillomania (TTM) is currently considered an OCD-spectrum disorder characterized by self-induced and recurrent loss of hair [177], and spontaneous barbering has been evaluated in mice of different background strains, and is suggested to be an animal model of TTM [167].…”

Estudos de associação genética no transtorno obsessivo-compulsivo

“…World et al found a preferential transmission of the G861 allele for OCD 24 and confirmed these findings in a longitudinal study 25 . Camarena et al also found a preferential transmission of the variant G861 C861 compared to the group with the highest scores of the YBOCS (Yale-Brown Obsessive Compulsive Scale), although no association was found with OCD 26 .…”